Language：English   Publishing type：Research paper (scientific journal)  

Tissue engineering requires growth factors, cells and a scaffold to permit effective tissue regeneration. This study aimed to develop a scaffold with a focus on immobilizing growth factors within gelatin. We focused on the extracellular matrix and developed a heparin-conjugated gelatin (Hep-gela). Conjugation was confirmed using the alcian blue assay and x-ray diffraction patterns. The mechanical strength and stability of the Hep-gela gel in protease solution were improved compared with collagen gel. Hep-gela was able to immobilize vascular endothelial growth factor (VEGF) even in the presence of albumin, with an efficiency of 54.2%. Immobilized VEGF promoted proliferation of human umbilical vein endothelial cells. Hep-gela-immobilized VEGF maintained its native biological activity. In summary, Hep-gela has the potential to become an effective material in the field of regenerative medicine.

DOI： 10.1016/j.jbiosc.2012.11.011

Language：English   Publishing type：Research paper (scientific journal)  

Growth factor (GF)-immobilizable materials were developed as a practical hepatocyte transplantation method for reconstructing a tissue-like structure in liver tissue engineering. Two GF-immobilizable scaffolds, namely single hepatocyte-embedded, heparin-immobilized, collagen-gel-filled polyurethane foam, and hepatocyte spheroid-embedded, heparin-immobilized, collagen-gel-filled polyurethane foam were developed by covalently incorporating heparin into collagen gel, using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide/N-hydroxysuccinimide for hepatocyte transplantation. Seventy percent partial hepatectomy (PH) was performed at the same time after hepatocyte transplantation. Angiogenesis efficiency and viability of transplanted cells are discussed in terms of normalized hemoglobin content, nuclear density and histological observations after transplantation. In summary, the normalized hemoglobin content and viability of transplanted cells were higher in GF-immobilized scaffolds with PH pretreatment than in the other scaffolds with/without PH pretreatment. These materials have the potential for in vivo hepatocyte transplantation, as GFs released from remnant liver were easily incorporated into the heparin-immobilized collagen gel system. These GF–heparin complexes may promote the survival of embedded cells. Furthermore, the transplantation of spheroids promoted increased angiogenesis compared with hepatocytes, and resulted in sufficient vascularization for cell survival.

DOI： http://dx.doi.org/10.1016/j.bej.2012.09.007

Language：English   Publishing type：Research paper (scientific journal)  

The construction of a functional liver-tissue equivalent using tissue engineering is a very important goal because the liver is a central organ in the body. However, the construction of functional organ-scale liver tissue is impossible because it requires a high-density blood vessel network. In this study, we focused on decellularization technology to solve this problem. Decellularized liver tissue with a fine vascular tree network template was obtained using Triton X-100. The distance between each vascular structure was less than 1 mm. Endothelialization of the blood vessel network with human umbilical vein endothelial cells (HUVECs) was successfully performed without any leakage of HUVECs to the outside of the vessel structure. Furthermore, hepatocytes/spheroids could be located around the blood vessel structure. This study indicates that decellularized liver tissue is a potential scaffold for creating a practical liver tissue using tissue engineering technology.

DOI： 10.1016/j.jbiosc.2012.05.022

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DOI： 10.1016/j.jbiosc.2011.05.003

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DOI： 10.1016/j.bej.2010.09.003

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DOI： doi:10.1016/j.jbiosc.2010.01.016

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DOI： 10.1016/j.bej.2009.10.003

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DOI： 10.1016/j.bej.2009.06.012

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DOI： 10.1016/j.bej.2009.05.017

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DOI： 10.1016/j.biomaterials.2004.11.043

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DOI： 10.1021/ie049354f

DOI： 10.1080/00219592.2023.2204899

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Language：English   Publisher：Biomaterials Advances  

Subcutaneous transplantation aims to enhance the growth and functionality of transplanted cells for therapeutic outcomes in tissue engineering. However, the limited subcutaneous vascular network poses a challenge. Conventional methods involve co-transplantation with endothelial cells or angiogenic scaffold implantation, but they have drawbacks like tissue inflammation, compromised endothelial cell functionality, and the risk of repeated scaffold transplantation. Effective techniques are needed to overcome these challenges. This study explores the potential of G/O-NGD, a gel-in-oil nanogel dispersion, as a transdermal carrier of proliferative factors to promote angiogenesis in subcutaneous graft beds before cell transplantation. We observed robust subcutaneous angiogenesis by delivering varying amounts of bFGF using the G/O-NGD emulsion. Quantitative analysis of several parameters confirmed the efficacy of this method for building a subcutaneous vascular network. G/O-NGD is a biodegradable material that facilitates localized transdermal delivery of bFGF while maintaining its activity. The findings of this study have significant implications in both medical and industrial fields.

DOI： 10.1016/j.bioadv.2023.213628

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Language：English   Publishing type：Research paper (scientific journal)  

Subcutaneous transplantation aims to enhance the growth and functionality of transplanted cells for therapeutic outcomes in tissue engineering. However, the limited subcutaneous vascular network poses a challenge. Conventional methods involve co-transplantation with endothelial cells or angiogenic scaffold implantation, but they have drawbacks like tissue inflammation, compromised endothelial cell functionality, and the risk of repeated scaffold transplantation. Effective techniques are needed to overcome these challenges. This study explores the potential of G/O-NGD, a gel-in-oil nanogel dispersion, as a transdermal carrier of proliferative factors to promote angiogenesis in subcutaneous graft beds before cell transplantation. We observed robust subcutaneous angiogenesis by delivering varying amounts of bFGF using the G/O-NGD emulsion. Quantitative analysis of several parameters confirmed the efficacy of this method for building a subcutaneous vascular network. G/O-NGD is a biodegradable material that facilitates localized transdermal delivery of bFGF while maintaining its activity. The findings of this study have significant implications in both medical and industrial fields.

DOI： https://doi.org/10.1016/j.bioadv.2023.213628

Language：English   Publisher：Biomedicines  

Oxygen is one of the essential requirements for cell survival, retention, and proliferation. The field of regenerative medicine and tissue engineering (TE) has realized considerable achievements for the regeneration of tissues. However, tissue regeneration still lacks the full functionality of solid organ implantations; limited cell survival and retention due to oxidative stress and hypoxia in the deeper parts of tissues remains a perpetual challenge. Especially prior to neovascularization, hypoxia is a major limiting factor, since oxygen delivery becomes crucial for cell survival throughout the tissue-engineered construct. Oxygen diffusion is generally limited in the range 100–200 μm of the thickness of a scaffold, and the cells located beyond this distance face oxygen deprivation, which ultimately leads to hypoxia. Furthermore, before achieving functional anastomosis, implanted tissues will be depleted of oxygen, resulting in hypoxia (<5% dissolved oxygen) followed by anoxic (<0.5% dissolved oxygen) microenvironments. Different types of approaches have been adopted to establish a sustained oxygen supply both in vitro and in vivo. In this review, we have summarized the recent developments in oxygen-generating and/or releasing biomaterials for enhancing cell survival in vitro, as well as for promoting soft and hard tissue repair, including skin, heart, nerve, pancreas, muscle, and bone tissues in vivo. In addition, redox-scavenging biomaterials and oxygenated scaffolds have also been highlighted. The surveyed results have shown significant promise in oxygen-producing biomaterials and oxygen carriers for enhancing cell functionality for regenerative medicine and TE applications. Taken together, this review provides a detailed overview of newer approaches and technologies for oxygen production, as well as their applications for bio-related disciplines.

DOI： 10.3390/biomedicines11061592

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Oxygen is one of the essential requirements for cell survival, retention, and proliferation. The field of regenerative medicine and tissue engineering (TE) has realized considerable achievements for the regeneration of tissues. However, tissue regeneration still lacks the full functionality of solid organ implantations; limited cell survival and retention due to oxidative stress and hypoxia in the deeper parts of tissues remains a perpetual challenge. Especially prior to neovascularization, hypoxia is a major limiting factor, since oxygen delivery becomes crucial for cell survival throughout the tissue-engineered construct. Oxygen diffusion is generally limited in the range 100–200 μm of the thickness of a scaffold, and the cells located beyond this distance face oxygen deprivation, which ultimately leads to hypoxia. Furthermore, before achieving functional anastomosis, implanted tissues will be depleted of oxygen, resulting in hypoxia (<5% dissolved oxygen) followed by anoxic (<0.5% dissolved oxygen) microenvironments. Different types of approaches have been adopted to establish a sustained oxygen supply both in vitro and in vivo. In this review, we have summarized the recent developments in oxygen-generating and/or releasing biomaterials for enhancing cell survival in vitro, as well as for promoting soft and hard tissue repair, including skin, heart, nerve, pancreas, muscle, and bone tissues in vivo. In addition, redox-scavenging biomaterials and oxygenated scaffolds have also been highlighted. The surveyed results have shown significant promise in oxygen-producing biomaterials and oxygen carriers for enhancing cell functionality for regenerative medicine and TE applications. Taken together, this review provides a detailed overview of newer approaches and technologies for oxygen production, as well as their applications for bio-related disciplines.

DOI： https://doi.org/10.3390/biomedicines11061592

Language：English   Publishing type：Research paper (scientific journal)  

Injuries to the nervous system a 1 ccount for the widespread morbidity, mortality, and discomfort worldwide. Artificial nerve guidance conduits (NGCs) offer promising platform for nerve reconstruction, however, they require extracellular matrix (ECM)-like features to better mimic the in vivo microenvironment. Consequently, this research was aimed to fabricate heparin/growth factors (GFs)-immobilized artificial NGCs. Heparin was covalently immobilized onto aligned electrospun polycaprolactone/gelatin (PCL/Gel) nanofibers. Thereafter, basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) were preferentially immobilized on heparinized nanofibers; the immobilization efficiency of GFs was found to be 50% with respect to (w.r.t.) their initial loaded amounts. The in vivo implantation of NGCs in a sciatic nerve defect model revealed the successful retention (~10% w.r.t the initial loaded amount) and bioactivity of NGF for up to 5 days. The permeability of bovine serum albumin (BSA) from nanofibrous membranes was further assessed and was found to be comparable with the commercialized cellulose acetate membranes. The bioactivity of NGCs was assessed in a sciatic nerve defect model in rats for short-term (1week) and long-term (1-month). The NGCs displayed good structural stability and biocompatibility in vivo. The in vivo evaluation revealed the accumulation of host cells into the transplanted NGCs. Taken together; these heparin/GFs-immobilized artificial NGCs may have broad implications for nerve regeneration and related tissue engineering disciplines.

DOI： https://doi.org/10.1007/s42765-022-00244-6

Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

In this article the affiliation details for Author Muhammad Shafiq were incorrectly given. They should have been assigned as shown below. The original article has been corrected. Department of Chemical Engineering, Faculty of Engineering, Graduate School, Kyushu University, 744 Motooka, Nishi-Ku, Fukuoka, 819–0395, Japan Department of Biotechnology, Faculty of Science and Technology, University of Central Punjab (UCP), Lahore, 54,000, Pakistan.

DOI： 10.1007/s42765-023-00261-z

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Other Link： https://link.springer.com/article/10.1007/s42765-023-00261-z/fulltext.html

Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Injuries to the nervous system account for the widespread morbidity, mortality, and discomfort worldwide. Artificial nerve guidance conduits (NGCs) offer a promising platform for nerve reconstruction, however, they require extracellular matrix (ECM)-like features to better mimic the in vivo microenvironment. Consequently, this research was aimed to fabricate heparin/growth factors (GFs)-immobilized artificial NGCs. Heparin was covalently immobilized onto aligned electrospun polycaprolactone/gelatin (PCL/Gel) nanofibers. Thereafter, basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) were preferentially immobilized on heparinized nanofibers; the immobilization efficiency of GFs was found to be 50% with respect to (w.r.t.) their initial loaded amounts. The in vivo implantation of NGCs in a sciatic nerve defect model revealed the successful retention (~ 10% w.r.t the initial loaded amount) and bioactivity of NGF for up to 5 days. The permeability of bovine serum albumin (BSA) from nanofibrous membranes was further assessed and found to be comparable with the commercialized cellulose acetate membranes. The bioactivity of NGCs was assessed in a sciatic nerve defect model in rats for short-term (1 week) and long-term (1-month). The NGCs displayed good structural stability and biocompatibility in vivo. The in vivo evaluation revealed the accumulation of host cells into the transplanted NGCs. Taken together; these heparin/GFs-immobilized artificial NGCs may have broad implications for nerve regeneration and related tissue engineering disciplines. Graphical Abstract: [Figure not available: see fulltext.].

DOI： 10.1007/s42765-022-00244-6

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Other Link： https://link.springer.com/article/10.1007/s42765-022-00244-6/fulltext.html

Language：English   Publisher：ACS Omega  

Ultraviolet (UV) radiation from the sun or artificial sources is one of the primary causes of skin damage, including sunburns, tanning, erythema, and skin cancer. Among the three different types of UV rays, UVB rays have a medium wavelength that can penetrate the epidermal layer of the skin, resulting in sunburn, suntan, blistering, and melanoma in case of chronic exposure. This study aimed to evaluate the preventive and therapeutic effects of a gel-in-oil nanogel dispersion (G/O-NGD) as a transdermal delivery biomolecular carrier for skin damage caused by UVB light. The efficacy of this carrier against UVB-induced skin damage was investigated in vivo by delivering different growth factors (GFs) encapsulated in a G/O-NGD. Artificial UVB light was used to induce skin damage in nude mice, followed by the transdermal application of five GF [vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), transforming growth factor (TGF)-1, and insulin-like growth factor (IGF)-α]-immobilized G/O-NGD. Among these GFs, VEGF and bFGF promoted angiogenesis, while EGF, TGF-1, and IGF-α promoted the repair and regeneration of damaged cells. The results showed that G/O-NGD was superior to heparin-immobilized G/O-NGD in reducing UVB-induced skin damage, such as erythema, epidermal water reduction, inflammation, and dermis thickening. In addition, G/O-NGD could prevent and treat abnormal follicle proliferation caused by UVB rays and exhibited potential to repair lipid glands. Overall, our results demonstrate the potential of G/O-NGDs for the treatment of UVB-induced skin damage.

DOI： 10.1021/acsomega.2c07343

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Publisher：Composites Part B: Engineering  

Cardiovascular injuries cause huge morbidity and mortality worldwide. Arterial reconstructions are generally performed either by using native grafts or synthetic grafts, both of which are limited by several complications. Synthetic biodegradable polymers offer a promising platform, which may also be modified to foster in situ tissue regeneration through the recruitment of host cells. Vascular endothelial growth factor (VEGF) promotes endothelialization and neovascularization in vascular grafts, however, an overdose of VEGF may induce tumor-like vasculature, which requires alternative strategies. The objective of this study was to exploit prominin-1-derived VEGF-binding peptide (BP) to improve neovascularization and endothelialization, while stromal cell-derived factor 1-alpha (SDF-1α) peptide to encourage endogenous stem/progenitor cells mobilization and complement BP-mediated vascular remodeling. The BP and SDF-1α peptides were covalently conjugated with low molecular weight poly (ε-caprolactone) (LPCL) to afford LPCL-BP and LPCL-SDF-1α, respectively. Chemical analysis revealed successful modification of LPCL with peptides, which also displayed good cytocompatibility in vitro once blended along with high molecular weight PCL (HPCL). The bioactived vascular grafts were fabricated by blending LPCL-BP, LPCL-SDF-1α or dual peptide-polymer conjugates with HPCL. The in vivo tests of vascular grafts through rat abdominal aorta implantation model revealed that, compared with HPCL grafts, the dual peptides modified grafts exhibited superior patency and tissue regeneration at 4-week post-implantation, including stem cell recruitment, rapid endothelialization and functional SMC layer formation. Taken together, these results may have implications for the in situ regeneration of artificial blood vessels through the orchestration of host's responses and endogenous cell recruitment.

DOI： 10.1016/j.compositesb.2023.110504

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Language：English   Publishing type：Research paper (scientific journal)  

Ultraviolet (UV) radiation from the sun or artificial sources is one of the primary causes of skin damage, including sunburns, tanning, erythema, and skin cancer. Among the three different types of UV rays, UV-B rays have a medium wavelength that can penetrate the epidermal layer of the skin, resulting in sunburn, suntan, blistering, and melanoma in case of chronic exposure. This study aimed to evaluate the preventive and therapeutic effects of a gel-in-oil nanogel dispersion (G/O-NGD) as a transdermal delivery biomolecular carrier for skin damage caused by UVB light. The efficacy of this carrier against UVB-induced skin damage was investigated in vivo by delivering different growth factors (GFs) encapsulated in a G/O-NGD. Artificial UVB light was used to induce skin damage in nude mice, followed by the transdermal application of five GF (vascular endothelial growth factor [VEGF], basic fibroblast growth factor [bFGF], epidermal growth factor [EGF], transforming growth factor [TGF]-1, and insulin-like growth factor [IGF]- α)-immobilized G/O-NGD. Among these GFs, VEGF and bFGF promoted angiogenesis, while EGF, TGF-1, and IGF-α promoted the repair and regeneration of damaged cells. The results showed that G/O-NGD was superior to heparin-immobilized G/O-NGD in reducing UVB-induced skin damage, such as erythema, epidermal water reduction, inflammation, and dermis thickening. In addition, G/O-NGD could prevent and treat abnormal follicle proliferation caused by UVB rays, and exhibited potential to repair lipid glands. Overall, our results demonstrate the potential of G/O-NGDs for the treatment of UVB-induced skin damage.

DOI： https://doi.org/10.1021/acsomega.2c07343

Language：English   Publishing type：Research paper (scientific journal)  

Cardiovascular injuries cause huge morbidity and mortality worldwide. Arterial reconstructions are generally performed either by using native grafts or synthetic grafts, both of which are limited by several complications. Synthetic biodegradable polymers offer a promising platform, which may also be modified to foster in situ tissue regeneration through the recruitment of host cells. Vascular endothelial growth factor (VEGF) promotes endothelialization and neovascularization in vascular grafts, however, an overdose of VEGF may induce tumor-like vasculature, which requires alternative strategies. The objective of this study was to exploit prominin-1 derived VEGF-binding peptide (BP) to improve neovascularization and endothelialization, while stromal cell-derived factor 1-alpha (SDF-1α) peptide to encourage endogenous stem/progenitor cell mobilization and complement BPmediated vascular remodeling. The BP and SDF-1α peptides were covalently conjugated with low molecular weight poly (ε-caprolactone) (LPCL) to afford LPCL-BP and LPCL-SDF-1α copolymers, respectively. Chemical analysis revealed successful modification of LPCL with peptides, which also displayed good cytocompatibility in vitro once blended along with high molecular weight PCL (HPCL). The bioactived vascular grafts were fabricated by blending LPCL-BP, LPCL-SDF-1α or dual copolymers with HPCL. The in vivo tests of vascular grafts through rat abdominal aorta implantation model revealed that, compared with HPCL grafts, the dual peptides modified grafts exhibited superior patency and tissue regeneration at 4-week postimplantation, including stem cell recruitment, rapid endothelialization and functional SMC layer formation. Taken together, these results may have implications for the in situ regeneration of artificial blood vessels through the orchestration of host’s responses and endogenous cell recruitment.

Language：English   Publishing type：Research paper (scientific journal)  

Skin regeneration is hindered by poor vascularization, prolonged inflammation, and excessive scar tissue formation, which necessitate newer strategies to simultaneously induce blood vessel regeneration, resolve inflammation, and induce host cell recruitment. Concurrent deployment of multiple biological cues to realize synergistic reparative effects may be an enticing avenue for wound healing. Herein, we simultaneously deployed SDF (stromal cell-derived factor)-1α, VEGF (vascular endothelial growth factor)-binding peptide (BP), and GLP (glucagon like peptide)-1 analogue, liraglutide (LG) in core/shell poly(L-lactide-co-glycolide)/gelatin fibers to harness their synergistic effects for skin repair in healthy as well as diabetic wound models in rats. Microscopic techniques, such as SEM and TEM revealed fibrous and core/shell type morphology of membranes. Boyden chamber assay and scratch-wound assay displayed significant migration of HUVECs (human umbilical vein endothelial cells) in SDF-1α containing fibers. Subcutaneous implantation of membranes revealed higher cellular infiltration in SDF-1α loaded fibers, especially, those which were co-loaded with LG or BP. Implantation of membranes in an excisional wound model in healthy rats further showed significant and rapid wound closure in dual cues loaded groups as compared to control or single cue loaded groups. Similarly, the implantation of dressings in type 2 diabetes rat model revealed fast healing, skin appendages regeneration, and blood vessel regeneration in dual cues loaded fibers (SDF-1α/LG, SDF-1α/BP). Taken together, core/shell type fibers containing bioactive peptides significantly promoted wound repair in healthy as well as diabetic wound models in rats.

DOI： https://doi.org/10.1016/j.colsurfb.2023.113140

Language：English   Publisher：Colloids and Surfaces B: Biointerfaces  

Skin regeneration is hindered by poor vascularization, prolonged inflammation, and excessive scar tissue formation, which necessitate newer strategies to simultaneously induce blood vessel regeneration, resolve inflammation, and induce host cell recruitment. Concurrent deployment of multiple biological cues to realize synergistic reparative effects may be an enticing avenue for wound healing. Herein, we simultaneously deployed SDF (stromal cell-derived factor)− 1α, VEGF (vascular endothelial growth factor)-binding peptide (BP), and GLP (glucagon like peptide)− 1 analog, liraglutide (LG) in core/shell poly(L-lactide-co-glycolide)/gelatin fibers to harness their synergistic effects for skin repair in healthy as well as diabetic wound models in rats. Microscopic techniques, such as SEM and TEM revealed fibrous and core/shell type morphology of membranes. Boyden chamber assay and scratch-wound assay displayed significant migration of HUVECs (human umbilical vein endothelial cells) in SDF-1α containing fibers. Subcutaneous implantation of membranes revealed higher cellular infiltration in SDF-1α loaded fibers, especially, those which were co-loaded with LG or BP. Implantation of membranes in an excisional wound model in healthy rats further showed significant and rapid wound closure in dual cues loaded groups as compared to control or single cue loaded groups. Similarly, the implantation of dressings in type 2 diabetes rat model revealed fast healing, skin appendages regeneration, and blood vessel regeneration in dual cues loaded fibers (SDF-1α/LG, SDF-1α/BP). Taken together, core/shell type fibers containing bioactive peptides significantly promoted wound repair in healthy as well as diabetic wound models in rats.

DOI： 10.1016/j.colsurfb.2023.113140

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Language：English   Publishing type：Research paper (scientific journal)  

Excessive scar tissue formation along with bacterial infection, hemorrhage, and oxidative wound microenvironment pose adverse physiological and psychological effects on patients, which necessitate the advent of innovative anti-inflammatory, anti-bacterial, and anti-oxidative multifunctional wound dressings. The overarching objective of this study was to exploit bioactive glass (BG) and a natural anti-bacterial component namely “oregano essential oil (OEO)” to impart multifunctionality to poly(L-lactide-co-glycolide)/Gelatin (PLGA/Gel)-based nanofibrous dressings for excisional wound management. We performed a series of structural, morphological, and release studies as well as delineated angiogenic, hemostatic, anti-bacterial, and anti-oxidative properties of these bioactive dressings in vitro, which altogether revealed the beneficial effects of BG and OEO in terms of rapid hemostasis, improved chemotactic response, diminished bacterial colonization, and anti-inflammatory response. Impressively, in multiple injury models, including a rat tail-amputation model, an ear artery injury model, and a liver trauma model in rabbit in vivo, we reported BG-mediated rapid hemostasis. Moreover, dressings containing BG showed improved hemocompatibility and suppressed coagulation as revealed by activated partial thromboplastin assay (APTT) in vitro. In addition, the transplantation of these nanofibrous dressings in a full-thickness excisional wound model in rats showed significant tissue regeneration as evidenced by the more number of blood vessels, glands, and hair follicles, re-epithelialization, diminished inflammatory response, and less fibrotic tissue formation. Taken together our approach of simultaneously harnessing economical BG and OEO to enable multifunctionality to nanofibrous dressings for tissue repair may hold great promise for wound healing as well as the other bio-related disciplines.

DOI： https://doi.org/10.1016/j.smaim.2023.01.001

Publisher：Smart Materials in Medicine  

Excessive scar tissue formation along with bacterial infection, hemorrhage, and oxidative wound microenvironment pose adverse physiological and psychological effects on patients, which necessitate the advent of innovative anti-inflammatory, anti-bacterial, and anti-oxidative multifunctional wound dressings. The overarching objective of this study was to exploit bioactive glass (BG) and a natural anti-bacterial component namely “oregano essential oil (OEO)” to impart multifunctionality to poly(L-lactide-co-glycolide)/Gelatin (PLGA/Gel)-based nanofibrous dressings for excisional wound management. We performed a series of structural, morphological, and release studies as well as delineated angiogenic, hemostatic, anti-bacterial, and anti-oxidative properties of these bioactive dressings in vitro, which altogether revealed the beneficial effects of BG and OEO in terms of rapid hemostasis, improved chemotactic response, diminished bacterial colonization, and anti-inflammatory response. Impressively, in multiple injury models, including a rat tail-amputation model, an ear artery injury model, and a liver trauma model in rabbit in vivo, we reported BG-mediated rapid hemostasis. Moreover, dressings containing BG showed improved hemocompatibility and suppressed coagulation as revealed by activated partial thromboplastin assay (APTT) in vitro. In addition, the transplantation of these nanofibrous dressings in a full-thickness excisional wound model in rats showed significant tissue regeneration as evidenced by the more number of blood vessels, glands, and hair follicles, re-epithelialization, diminished inflammatory response, and less fibrotic tissue formation. Taken together our approach of simultaneously harnessing economical BG and OEO to enable multifunctionality to nanofibrous dressings for tissue repair may hold great promise for wound healing as well as other bio-related disciplines.

DOI： 10.1016/j.smaim.2023.01.001

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Language：English   Publishing type：Research paper (scientific journal)  

Purpose: At present,≥20% of patients experience clinically relevant postoperative pancreatic fstula (POPF) after distal pancreatectomy (DP).
Methods: We developed a new bioabsorbable pancreatic clip (BioPaC) made of polycaprolactone that does not crush the pancreatic parenchyma during occlusion of the pancreatic stump. We confrmed the efcacy of this BioPac in a porcine DP model and compared it to a linear stapling device (Reinforce®).
Results: Pigs were killed at 1 month after DP. In the BioPaC group, all swine (n=3) survived well without POPF. In the Reinforce® group (n=2), one pig died early at postoperative day 7 with Grade C POPF (amylase 43 700 U/l), and the other survived until 1 month at scarifcation with biochemical leakage of POPF (amylase 3 725 U/l). Pathologically, the main pancreatic duct and pancreatic parenchyma were well closed by BioPaC.
Conclusion: The newly developed BioPaC is efective in a porcine DP model.

DOI： https://doi.org/10.1007/s00595-021-02435-x

Language：English   Publisher：シュプリンガー・ジャパン(株)  

膵尾部切除に際して膵断端閉塞中に膵実質を破断させないようなポリカプロラクトン製の新規生体吸収性膵臓クリップ(BioPaC)を作製し、その有効性を検討した。体重25～30kgの健常ブタを用いて実験を行い、手術では膵尾部を脾静脈と後腹膜から切離した後、脾膵葉の最も厚みのある部分を、BioPaCを用いて閉鎖した。対照にはReinforceを用いてBioPaCと同様の処理を施した。BioPaCは長さ59mm、高さ6mm、厚み5mm、クランプ時の幅16mm、クランプ時のギャップ4mmという構造であった。Reinforceを使用したブタ2匹のうち1匹は術後7日目に死亡し、グレードCの術後膵液漏(POPF)と診断された。もう1匹は術後30日まで生存したが、膵断端周囲に著明な腹腔内癒着が観察された。BioPaCを用いた3匹の術後経過は良好で、POPFの発症は認められなかった。病理学的所見ではBioPaCによって主膵管と膵実質の閉鎖が得られていた。ブタ膵尾部切除モデルにおいてBioPaCは有効であることが示された。

Language：English   Publisher：Surgery Today  

Purpose: At present, ≥ 20% of patients experience clinically relevant postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP). Methods: We developed a new bioabsorbable pancreatic clip (BioPaC) made of polycaprolactone that does not crush the pancreatic parenchyma during occlusion of the pancreatic stump. We confirmed the efficacy of this BioPac in a porcine DP model and compared it to a linear stapling device (Reinforce®). Results: Pigs were killed at 1 month after DP. In the BioPaC group, all swine (n = 3) survived well without POPF. In the Reinforce® group (n = 2), one pig died early at postoperative day 7 with Grade C POPF (amylase 43 700 U/l), and the other survived until 1 month at scarification with biochemical leakage of POPF (amylase 3 725 U/l). Pathologically, the main pancreatic duct and pancreatic parenchyma were well closed by BioPaC. Conclusion: The newly developed BioPaC is effective in a porcine DP model.

DOI： 10.1007/s00595-021-02435-x

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Researchers have long awaited the technology to develop an in vitro kidney model. Here, we establish a rapid fabricating technique for kidney-like tissues (cysts) using a combination of or-gan-derived extracellular matrix (ECM) gel format culture system and a renal stem cell line (CHK-Q cells). CHK-Q cells, which are spontaneously immortalized from the renal stem cells of Chinese hamster, formed renal cyst-like structures in a type-I collagen gel sandwich culture on day 1 of culture. The cysts fused together and expanded while maintaining three-dimensional structures. The expression of genes related to kidney development and maturation was increased compared with that in a traditional monolayer. Under kidney-derived ECM (K-ECM) gel format culture system, cyst formation and maturation were induced rapidly. Gene expressions involved in cell polarities, especially for important material transporters (typical markers Slc5a1 and Kcnj1), were restored. K-ECM composition were important triggers for CHK-Q cells to promote kidney-like tissue formation and maturation. We have established a renal cyst model, which rapidly expressed mature kidney features, via the combination of K-ECM gel format culture system and CHK-Q cells.

DOI： https://doi.org/10.3390/gels8050312

Language：English   Publishing type：Research paper (scientific journal)  

Purpose. The aim of the present study was to develop a nanogel emulsion, as a minimally invasive, safe, and effective treatment alternative for posterior ocular diseases.
Methods. A gel-in-water (G/W) nanoemulsion was developed by ultrasonication using beeswax as an organogelator. Different physicochemical properties were evaluated along with particle size analysis by dynamic light scattering. In vitro biocompatibility of G/W nanoemulsion using rat hepatocytes and human umbilical vein endothelial cells (HUVECs) and in vivo corneal permeability as eye drops were investigated.
Results. The nanogel emulsion was monodispersed with a polydispersity index and particle diameter of approximately 0.2 and 200 nm, respectively. The zeta potential value of −8.1 mV suggested enhanced stability and improved retinal permeability of nanoparticles. The prepared nanoemulsion was found to be biocompatible with hepatocytes and HUVECs in vitro. Moreover, in vivo study demonstrated high permeability of G/W nanoemulsion to the retinal layer with no ocular irritation.
Conclusion. G/W nanoemulsions have the potential for topical drug delivery in the posterior eye segment with maximum therapeutic efficacy.
Translational relevance. Organogel nanodispersion is a new concept to deliver hydrophobic drugs to the posterior segment of eyes as a novel drug delivery system.

DOI： https://doi.org/10.1167/tvst.11.5.16

Language：English   Publisher：Translational Vision Science and Technology  

Purpose: The aim of this study was to develop a nanogel emulsion as a minimally invasive, safe, and effective treatment alternative for posterior ocular diseases. Methods: A gel-in-water (G/W) nanoemulsion was developed by ultrasonication using beeswax as an organogelator. Different physicochemical properties were evaluated along with particle size analysis by dynamic light scattering. In vitro biocompatibility of G/W nanoemulsion using rat hepatocytes and human umbilical vein endothelial cells (HUVECs) and in vivo corneal permeability as eye drops were investigated. Results: The nanogel emulsion was monodispersed with a polydispersity index and particle diameter of approximately 0.2 and 200 nm, respectively. The zeta potential value of −8.1 mV suggested enhanced stability and improved retinal permeability of nanopar-ticles. The prepared nanoemulsion was found to be biocompatible with hepatocytes and HUVECs in vitro. Moreover, in vivo study demonstrated high permeability of G/W nanoemulsion to the retinal layer with no ocular irritation. Conclusions: G/W nanoemulsions have the potential for topical drug delivery in the posterior eye segment with maximum therapeutic efficacy. Translational Relevance: Organogel nanodispersion is a new concept to deliver hydrophobic drugs to the posterior segment of eyes as a novel drug delivery system.

DOI： 10.1167/tvst.11.5.16

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PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

Researchers have long awaited the technology to develop an in vitro kidney model. Here, we establish a rapid fabricating technique for kidney-like tissues (cysts) using a combination of an organ-derived extracellular matrix (ECM) gel format culture system and a renal stem cell line (CHK-Q cells). CHK-Q cells, which are spontaneously immortalized from the renal stem cells of the Chinese hamster, formed renal cyst-like structures in a type-I collagen gel sandwich culture on day 1 of culture. The cysts fused together and expanded while maintaining three-dimensional structures. The expression of genes related to kidney development and maturation was increased compared with that in a traditional monolayer. Under the kidney-derived ECM (K-ECM) gel format culture system, cyst formation and maturation were induced rapidly. Gene expressions involved in cell polarities, especially for important material transporters (typical markers Slc5a1 and Kcnj1), were restored. K-ECM composition was an important trigger for CHK-Q cells to promote kidney-like tissue formation and maturation. We have established a renal cyst model which rapidly expressed mature kidney features via the combination of K-ECM gel format culture system and CHK-Q cells.

DOI： 10.3390/gels8050312

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PubMed

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Language：Japanese   Publisher：(一社)日本外科学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Organogels are semi-solid systems that can gel organic liquids at low concentrations. The use of organogels in drug delivery has grown rapidly in the last decade owing to their fibrous microstructure and suitability for different routes of administration. The current study is characterized by nanogel dispersion (NGD) development based on emulsion technology. The efficiency of this organogel based NGD as a carrier for anticancer drugs was assessed both in vitro and in vivo. 12-Hydroxystearic acid formed an organogel with lipiodol and encapsulated the anticancer drug paclitaxel. The gel-in-water (G/W) nanodispersion was prepared via ultrasonication and stabilized by a nonionic surfactant. The results showed that the organogel enabled sustained drug release from G/W nanodispersion over time, along with enhanced cellular uptake. The prepared G/W nanodispersion was found to be biocompatible with mouse hepatocytes and fibroblast cells in vitro, whereas paclitaxel-loaded G/W nanodispersion showed cytotoxicity (*p <0.05) against lung cancer (A549) cell lines. Similarly, intravenous administration of paclitaxel-loaded G/W nanodispersion exerts an anticancer effect against lung cancer in vivo, with a significant decrease in tumor volume (*p <0.05). Therefore, the proposed G/W nanodispersion could be a promising carrier for chemotherapy agents with sustained drug release and better therapeutic outcomes against cancer.

DOI： https://doi.org/10.1016/j.jbiosc.2021.10.001

Language：English   Publisher：Journal of Bioscience and Bioengineering  

Organogels are semi-solid systems that can gel organic liquids at low concentrations. The use of organogels in drug delivery has grown rapidly in the last decade owing to their fibrous microstructure and suitability for different routes of administration. The current study is characterized by nanogel dispersion (NGD) development based on emulsion technology. The efficiency of this organogel based NGD as a carrier for anticancer drugs was assessed both in vitro and in vivo. 12-Hydroxystearic acid formed an organogel with lipiodol and encapsulated the anticancer drug paclitaxel. The gel-in-water (G/W) nanodispersion was prepared via ultrasonication and stabilized by a nonionic surfactant. The results showed that the organogel enabled sustained drug release from G/W nanodispersion over time, along with enhanced cellular uptake. The prepared G/W nanodispersion was found to be biocompatible with mouse hepatocytes and fibroblast cells in vitro, whereas paclitaxel-loaded G/W nanodispersion showed cytotoxicity (p <0.05) against lung cancer (A549) cell lines. Similarly, intravenous administration of paclitaxel-loaded G/W nanodispersion exerts an anticancer effect against lung cancer in vivo, with a significant decrease in tumor volume (p <0.05). Therefore, the proposed G/W nanodispersion could be a promising carrier for chemotherapy agents with sustained drug release and better therapeutic outcomes against cancer.

DOI： 10.1016/j.jbiosc.2021.10.001

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PubMed

Language：English   Publisher：(公社)日本生物工学会  

抗癌薬輸送体としてのナノゲル分散(NGD)ベースのオルガノゲル(OG)の効率をin vitroとin vivoで評価した。12-ヒドロキシステアリン酸とリピオドールでOGを形成させて抗癌薬パクリタキセル(PTX)をカプセル化した。gel-in-water(G/W)ナノ分散液は超音波処理で調製し、非イオン性界面活性剤で安定化させた。このOGは細胞への取り込みを促進すると共に、G/Wナノ分散からの持続的薬物放出を経時的に可能にした。in vitroにて、調製したG/Wナノ分散液はマウス肝細胞と線維芽細胞に対して生体適合性を示し、PTX負荷のG/Wナノ分散液は肺癌A549細胞株に対して有意に細胞毒性を示した。同様に、PTX負荷G/Wナノ分散液のin vivoマウス静脈内投与は肺癌に対して抗癌効果を示し、腫瘍体積が有意に減少した。

Language：English   Publishing type：Research paper (scientific journal)  

The effective delivery of anti-cancer drugs with minimal side effects and better therapeutic efficacy has remained an active area of research for many decades. Organogels have gained attention in recent years due to their high bioavailability, no first-pass metabolism, and rapid action. Considering this, in the current study an organogel based nanoemulsion was developed aiming to effectively deliver hydrophobic drugs via encapsulation within in situ gellable organogel droplets, termed as gel-in-water (G/W) nanoemulsion. G/W nanoemulsion was prepared using a combination of lipiodol and organogeltor 12-Hydroxystearic acid (12-HSA) as inner gel phase; dispersed in water by ultrasonication and stabilized with polyoxyethylene hydrogenated castor oil (HCO-60) as surfactant. The prepared nanoemulsion showed high drug loading efficiency (≈ 97%) with a mean diameter of 206 nm. Lower polydispersity index (PdI) value (≈ 0.1) suggests monodispersed nature of G/W nanoemulsion in the continuous phase. G/W nanoemulsion was found stable over six months in terms of particle size, zeta potential and pH at different storage temperatures. There was no cytotoxic effect of prepared G/W nanoemulsion on primary hepatocytes in vitro. In contrast, paclitaxel-loaded G/W showed a significant decrease in melanoma cell growth (*p <0.05) both in vitro and in vivo. Our results support the hypothesis that organogel based nanoemulsions can be a promising drug delivery system.

DOI： https://doi.org/10.1016/j.msec.2021.112076

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.reth.2020.10.002.

Language：English   Publishing type：Research paper (scientific journal)  

[Introduction] Cells have various applications in biomedical research. Cryopreservation is a cell-preservation technique that provides cells for such applications. After cryopreservation, sensitive cells, such as primary hepatocytes, suffer from low viability due to the physical damage caused by ice crystals, highlighting the need for better methods of cryopreservation to improve cell viability. Given the importance of effectively suppressing ice crystal formation to protect cellular structure, trehalose has attracted attention as cryoprotectant based on its ability to inhibit ice crystal formation; however, trehalose induces osmotic stress. Therefore, to establish a cell-cryopreservation technique, it is necessary to provide an optimal balance between the protective and damaging effects of trehalose.
[Methods] In this study, we evaluated the effects of osmotic stress and ice crystal formation on the viability and function of primary rat hepatocytes at wide range of trehalose concentration.
[Results] There was no osmotic stress at very low concentrations (2.6 μM) of trehalose, and 2.6 μM trehalose drives the formation of finer ice crystals, which are less damaging to the cell membrane. Furthermore, we found that the number of viable hepatocytes after cryopreservation were 70% higher under the 2.6 μM trehalose-supplemented conditions than under the dimethyl sulfoxide-supplemented conditions. Moreover, non-cryopreserved cells and cells cryopreserved with trehalose showed comparable intracellular dehydrogenase activity.
[Conclusions] We showed that trehalose at very low concentrations (2.6 μM) improved dramatically viability and liver function of hepatocyte after cryopreservation.

DOI： 10.1016/j.reth.2020.08.003.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： https://doi.org/10.1016/j.jbiosc.2019.09.004

Language：English   Publishing type：Research paper (scientific journal)  

Endothelization of a tissue-engineered substrate is important for its application as an artificial vascular graft. Despite recent advancements in artificial graft fabrication, a graft of b5mmis difficult to fabricate owing to insufficient endothelization that results in thrombosis after transplantation. We aimed to perform a co-culture of adipose-derived mesenchymal stem cells (MSCs) with human umbilical vein endothelial cells (HUVECs) on antithrombogenic polycaprolactone (PCL)/heparin-gelatin co-spun nanofibers to evaluate the role of coculturing in promoting quick endothelization of vascular substrateswithout surface modification by growth factors or other ECM proteins that trigger the endothelization process. Using a co-axial electrospinning technique, we attempted to fabricate our scaffold balancing between mechanical properties and biocompatibility. Antithrombogenic characteristics were then imparted to the fabricated nanofiber substrate by grafting of heparin. Finally, we performed a co-culture of MSCs and HUVECs on the fabricated co-spun nanofiber substrate to obtain proper endothelization of our material under the in-vitro culture. Staining for CD-31 at seven days of culture revealed enhanced CD-31 expression under the co-culture condition; actin staining revealed healthy cobblestone HUVECmorphology, suggesting thatMSCs can aid in proper endothelization. Hence,we conclude that co-culture is effective for quick endothelization of vascular substrates.

DOI： https://doi.org/10.1016/j.ijbiomac.2020.02.163

Language：English   Publishing type：Research paper (scientific journal)  

The extracellular matrix (ECM) in a liver-specific extracellular matrix (L-ECM) scaffold facilitates hepatocyte viability and maintains hepatocyte functions in vitro. However, whether an intact composition of ECM is required for an efficient ECM-based substrate design remains to be clarified. In this study, two LECM hydrogels, namely L-ECM I and L-ECM II, were prepared by pepsin solubilization at 4 ℃ and 25 ℃, respectively. The solubility at 4 ℃ was 50% whereas that at 25 C was 95%, thus indicating well-preserved L-ECM. Analysis confirmed higher ECM protein components (especially collagen) in L-ECM II, along with denser fiber network and larger fiber diameter. L-ECM II gel exhibited high compression strength and suitable viscoelastic properties. Furthermore, hepatocytes in L-ECM II showed higher expression of liver specific functions in 3D culture and wider spread while maintaining the cell-cell contacts in 2D culture. Therefore, an intact L-ECM is important to realize effective substrates for liver tissue engineering.

DOI： https://doi.org/10.1016/j.reth.2019.08.006

Language：English   Publishing type：Research paper (scientific journal)  

In recent years, studies on liver graft construction using the decellularized liver as a template for transplantation therapy have attracted much attention. However, the therapeutic effect of constructed liver grafts in hepatic failure has not been evaluated. Therefore, we aimed to develop a novel evaluation system demonstrating the curative effect of a constructed liver graft in animals with hepatic failure. First, we developed a highly reproducible rat model of hepatic failure by combining 80% partial hepatectomy with warm ischemia. In this model, severity could be controlled by the warm ischemic period. We also constructed a liver graft by recellularization of decellularized liver, and confirmed the ammonia metabolic function in the graft in vitro as one of the most important functions for recovery from hepatic failure. The graft was then applied to our developed-hepatic failure rat model using a blood extracorporeal circulation system. In this application, the graft metabolized the ammonia in the blood of animals with hepatic failure and was thus suggested to be effective for the treatment of hepatic failure. In summary, a novel evaluation system for whole organ engineered-liver graft as a preliminary stage of transplantation was developed. This system was expected to provide much information about the curative effect of a constructed liver graft.

DOI： https://doi.org/10.1007/s10047-019-01106-6

Language：English   Publishing type：Research paper (scientific journal)  

A solubilized liver-specific extracellular matrix (L-ECM) substratum was obtained by decellularization of porcine liver using Triton X-100 and pepsin treatments. The L-ECM was able to immobilize hepatocyte growth factor at a high efficiency of 87%. L-ECM gelled spontaneously in a physiologically neutral environment. Primary hepatocytes embedded in the L-ECM gel showed a high albumin synthesis activity and EROD activity even at 3 weeks in culture. In addition, the L-ECM gel-embedded hepatocytes implanted subcutaneously into partial hepatectomized rats showed a high survival rate (18%) and formed a large liver tissue-like structure. Their efficiencies of EROD activity and large liver tissue-like structure formation were about twice those of collagen gel-embedded hepatocytes. Based on these results, we clarified the effectiveness of L-ECM gel as a substrate for hepatocyte culture and transplantation.

DOI： https://doi.org/10.1016/j.jbiosc.2019.02.014

Language：English   Publishing type：Research paper (scientific journal)  

We developed a new oil-based delivery system for transdermal protein delivery, a gel-in-oil (G/O) nanosuspension, where gelatin-based hydrogel was coated with hydrophobic surfactants. The high entrapment efficiency of a model protein, phycocyanin (PC), into nano-sized gelatin hydrogel particles was achieved. Spectroscopic evaluation of PC suggested that the G/O nanosuspension could retain the functional form of PC in isopropyl myristate. In vitro skin permeation studies showed that the G/O nanosuspension facilitated the delivery of PC through the stratum corneum of Yucatan micropig skin.

DOI： https://doi.org/10.1016/j.ijpharm.2019.118495

Language：English   Publishing type：Research paper (scientific journal)  

Aims: The main aim of our study was to examine the concentration of surfactant that can cause significant disruption of the resulting decellularized liver structure. Furthermore, it is our goal to
determine the suitable solvent that can boost the potential of each surfactant.
Methodology: The porcine liver disks of 8-mm diameter and 2-mm thickness were prepared. These were soaked in aqueous solution of either sodium dodecyl sulfate (SDS) or Triton X-100 (TX), and
placed on a rotational shaking machine (100 rpm).
Results: TX was unable to completely remove the cellular components under any of our experimental conditions. The salt concentration did not affect the decellularization in TX. The pH
buffer, however, was found to affect the decellularization. Also, in the solvent study, the conditions under which SDS effectively exerted power were not the salt concentration and pH, but the condition
that was close to water. We also confirmed that the shrinkage of tissue occurred when decellularization with 0.1% SDS in CMF-PBS. However, 0.1% SDS in distilled water didn't cause the
deformation of tissue. This is considered to be due to the low salt concentration of solvent.
Conclusion: This work establishes the concentration range of the surfactant that causes the collapse of the cellular structure during decellularization. In addition, the solvent suitable for each
surfactant has also been established.

Language：English   Publishing type：Research paper (scientific journal)  

Hydrogels and their medical applications in tissue engineering have been widely studied due to their three-dimensional network structure, biocompatibility, and cell adhesion. However, the development of an artificial bile duct to replace the recipient's tissue is still desired. Some challenges remain in the tissue engineering field, such as infection due to residual artifacts. In other words, at present, there are no established technologies for bile duct reconstruction as strength and biocompatibility problems. Therefore, this study investigated hydrogel as an artificial bile duct base material that can replace tissue without any risk of infectious diseases. First, an antibacterial agent (ABA), Finibax (an ABA used for the clinical treatment of biliary tract infection), was immobilized in gelatin using a crosslinking agent, and the antibacterial properties of the gel and its sustainability were tested. Furthermore, the immobilized amount and the improvement of the proliferation of the human umbilical vein endothelial cells (HUVECs) were cultured as the ABA-Gelatin hydrogel was introduced to prepare a 3D scaffold. Finally, we performed hematoxylin and eosin (H&E) staining after subcutaneous implantation in the rat. Overall, the ABA-Gelatin hydrogel was found to be viable for use in hydrogel applications for tissue engineering due to its good bactericidal ability, cell adhesion, and proliferation, as well as having no cytotoxicity to cells.

DOI： https://doi.org/10.3390/gels5020032

Language：English   Publishing type：Research paper (scientific journal)  

Accurate determination of the amount of glycosaminoglycans (GAGs) in a complex mixture of extracellular matrix (ECM) is important for tissue morphogenesis and homeostasis. The aim of the present study was to investigate an accurate, simple and sensitive alcian blue (AB) method for quantifying heparin in biological samples. A method for analyzing heparin was developed and parameters such as volume, precipitation time, solvent component, and solubility time were evaluated. The AB dye and heparin samples were allowed to react at 4 ℃ for 24 h. The heparin-AB complex was dissolved in 25 N NaOH and 2-Aminoethanol (1:24 v/v). The optical density of the solution was analyzed by UV-Vis spectrometry at 620 nm. The modified AB method was validated in accordance with U.S. Food and Drug Administration guidelines. The limit of detection was found to be 2.95 µg/mL. Intraday and interday precision ranged between 2.14–4.83% and 3.16–7.02% (n = 9), respectively. Overall recovery for three concentration levels varied between 97 ± 3.5%, confirming good accuracy. In addition, this study has discovered the interdisciplinary nature of protein detection using the AB method. The basis for this investigation was that the fibrous protein inhibits heparin-AB complex whereas globular protein does not. Further, we measured the content of sulfated GAGs (sGAGs; expressed as heparin equivalent) in the ECM of decellularized porcine liver. In conclusion, the AB method may be used for the quantitative analysis of heparin in ECM scaffolds for tissue engineering applications.

DOI： https://doi.org/10.3390/jfb10020019

Language：English   Publishing type：Research paper (scientific journal)  

Fabrication of functional scaffolds is one of the main goals of tissue engineering, particularly scaffolds mimicking the native extracellular matrix (ECM) and stimulating a microenvironment that supports cell growth and function. In this study, a scaffold was developed using liver-derived ECM (L-ECM), gelatin, and polycaprolactone (PCL) by conventional electrospinning. This study aimed to improve the gelatin-PCL nanofiber blend by incorporating L-ECM. The morphology of the nanofibrous scaffold was investigated by scanning electron microscopy. Characterizations such as Fourier transform infrared spectroscopy (FTIR), tensile strength test, and water contact angle analysis revealed the favorable characteristics of the scaffold. Particularly, the FTIR spectra confirmed the presence of L-ECM, gelatin, and PCL, even after crosslinking treatment, while tensile strength analysis revealed suitable mechanical properties and water contact angle measurement showed the improved hydrophilic characteristics of the scaffold. The biocompatibility of the composite nanofibers was evaluated by in vitro culture of primary hepatocytes. Phase-contrast microscope images verified that the L-ECM nanofibers improved hepatocyte adhesion and facilitated the formation of a tissue-like structure. Moreover, high liver-specific functions were obtained in L-ECM nanofibers compared to gelatin/PCL nanofibers. Thus, L-ECM nanofibers can be used in tissue engineering, particularly in liver regeneration.

DOI： doi.org/10.1016/j.mtla.2018.11.014

Language：English   Publishing type：Research paper (scientific journal)  

The decellularization of organs has attracted attention as a new functional methodology for regenerative medicine based on tissue engineering. In previous work we developed an L-ECM (Extracellular Matrix) as a substrate-solubilized decellularized liver and demonstrated its effectiveness as a substrate for culturing and transplantation. Importantly, the physical properties of the substrate constitute important factors that control cell behavior. In this study, we aimed to quantify the physical properties of L-ECM and L-ECM gels. L-ECM was prepared as a liver-specific matrix substrate from solubilized decellularized porcine liver. In comparison to type I collagen, L-ECM yielded a lower elasticity and exhibited an abrupt decrease in its elastic modulus at 37 °C. Its elastic modulus increased at increased temperatures, and the storage elastic modulus value never fell below the loss modulus value. An increase in the gel concentration of L-ECM resulted in a decrease in the biodegradation rate and in an increase in mechanical strength. The reported properties of L-ECM gel (10 mg/mL) were equivalent to those of collagen gel (3 mg/mL), which is commonly used in regenerative medicine and gel cultures. Based on reported findings, the physical properties of the novel functional substrate for culturing and regenerative medicine L-ECM were quantified.

DOI： doi:10.3390/gels4020039

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1021/acsami.7b13727.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jbiosc.2017.04.018

Language：English   Publishing type：Research paper (international conference proceedings)  

Development of a novel therapeutic treatment is indispensable for the life-saving of severe liver failure patients. In this study, a hybrid artificial liver support system consisting of a porous substrate packed bed type module in which hepatocytes spheroid was immobilized was developed. In preclinical animal experiments using warm ischemic liver failure pigs, this system realized high expression of liver functions and remarkable prolongation of survival time. On the other hand, a prototype of Whole Liver Engineered-Liver for transplantation was constructed using rats as model animals. Blood ammonia was well metabolized in blood circulation culture containing this graft. Furthermore, the survival time of liver failure rats was applied was markedly prolonged by applying this graft. From the above results, the effectiveness of the practical hybrid artificial liver support system and Whole Organ Engineered-Liver graft was demonstrated.

Language：English   Publishing type：Research paper (scientific journal)  

Conventionally, some bioartificial liver devices are used with separate plasmapheresis unit to separate out plasma from whole blood and adsorbent column to detoxify plasma before it passes through a hepatocytes-laden bioreactor. We aim to develop a hybrid bioreactor that integrates the separate modules in one compact design improving the efficacy of the cryogel based bioreactor as a bioartificial liver support. A plasma separation membrane and an activated carbon cloth are placed over a HepG2-loaded cryogel scaffold in a three-chambered bioreactor design. This bioreactor is consequently connected extracorporeally to a rat model of acute liver failure for 3 h and major biochemical parameters studied. Bilirubin and aspartate transaminase showed a percentage decrease of 20–60% in the integrated bioreactor as opposed to 5–15% in the conventional setup. Urea and ammonia levels which showed negligible change in the conventional setup increase (40%) and decrease (18%), respectively in the integrated system. Also, an overall increase of 5% in human albumin in rat plasma indicated bioreactor functionality in terms of synthetic functions. These results were corroborated by offline evaluation of patient plasma. Hence, integrating the plasmapheresis and adsorbent units with the bioreactor module in one compact design improves the efficacy of the bioartificial liver device.

DOI： DOI: 10.1038/srep40323

Language：English   Publishing type：Research paper (scientific journal)  

Good mass transfer and high cell density culture are required for bioreactors using animal cells. These criteria can be met by fabricating a tissue in the bioreactor. In the present study, polypod particles were prepared using agarose, carrageenan, calcium alginate, and hydroxyapatite. The particles were then packed into reactors, and the reactors were lled with enzymatically cross-linked gelatin. Reactors with ow channels were then obtained upon dissolution of the gel particles. Cell adhesion, growth, and expression of organ (liver) function in the reactor were subsequently examined. Experiment using CHO-K1 cells suggested that the cells adhered and grew on the internal surface of the ow channels. HepG2 cells inoculated into the reactor expressed liver-specic functions over the 3-day culture period examined. Thus, the current ndings demonstrate that the method developed can be applied to fabricate bioreactors to provide physiologically active substances and medical treatments for tissue engineering. Furthermore, this method was extended to the preparation of a hydroxyapatite-packed reactor by combining calcium alginate gel particles and hydroxyapatite. Therefore, this technique is expected to be applicable to both soft tissue models and hard tissue models such as bone.

DOI： DOI:10.14326/abe.5.105

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi:10.1016/j.jbiosc.2015.11.006

Language：English   Publishing type：Research paper (scientific journal)  

Recently, decellularized liver (DC-liver) was developed as a scaffold for the creation of liver tissue because DC-liver has a vascular structure that is used for oxygen delivery. The structure was evaluated by the appearance of molded resin. In the present study, three-dimensional computed tomography was used to obtain images of the vascular structure. Imaging at the hepatic lobule level was achieved by coating the molded resin with contrast dye or gold. We defined indexes to evaluate blood vessel conformation and structure. The data for each index were obtained from the images. These data suggest that DC-liver has a fine vascular structure quantitatively similar to that of native liver. This method is valuable for the development of whole liver engineering.

DOI： DOI:10.14326/abe.4.179

Language：English   Publishing type：Research paper (scientific journal)  

Hepatocyte transplantation is a potential therapy for treating various liver diseases. However, oxygen shortage and loss of hepatocyte function becomes a limitation following hepatocyte transplantation. To overcome this problem, we developed a hybrid organoid, consisting of growth factor (GF)-immobilizable gel particles combined with hepatocytes. Benefits of the hybrid organoid were evaluated in three groups: (1) hybrid organoid consisting of cells and GF-immobilizable gel particles (HG-C); (2) hybrid organoid consisting of cells and gel particles (G-C); and (3) cells suspended in collagen (C-C). We found liver specific functions of HG-C were maintained longer than in the other conditions during in vitro culture. Furthermore, after transplantation, HG-C was effective in maintaining viability of transplanted hepatocytes and promoting angiogenesis around the hepatocytes. In summary, transplantation of HG-C is a potential method for future liver tissue engineering.

DOI： 10.1016/j.jbiosc.2015.01.004

Language：English   Publishing type：Research paper (scientific journal)  

DOI： DOI: 10.1002/mabi.201400306

Language：English   Publishing type：Research paper (scientific journal)  

The objective of this study was to examine the validity of estimating cell number using the water-soluble tetrazolium salts-8 (WST-8) assay for normal cells. The changes in mitochondrial activity of human umbilical vein endothelial cells (HUVECs) cultured under various culture conditions were evaluated using this assay. We found that cell counting of HUVECs by the WST-8 assay was not accurate under certain culture conditions, because the mitochondrial activity per cell changed depending on culture duration and medium composition. When charcoal/dextran-treated fetal bovine serum (FBS) -supplemented medium was used in cultures, the mitochondrial activity per cell was similar both in the presence and in the absence of vascular endothelial growth factor (VEGF). Furthermore, the mitochondrial activity did not affect the proliferative activity of cells, because we observed VEGF-dependent proliferation of HUVECs in this medium. For precise evaluation of cell number using the WST-8 assay, it is important to consider the accuracy of the assay results. Thus, a reliable method of cell counting using WST-8 needs to be developed.

DOI： http://dx.doi.org/10.14326/abe.3.1

Language：English   Publishing type：Research paper (scientific journal)  

Although immobilization of growth factors (GFs) on culture substrates has been investigated as a cell culture technique, quantification of the bioactive stability of immobilized GFs has not been studied in detail. We developed a system of measuring GF stability using heparin-immobilized collagen substrate, vascular endothelial growth factor (VEGF). and human umbilical vein endothelial cells (HUVECs). VEGF solution was added to a heparin-crosslinked substrate and immobilized on the substrate. HUVECs were cultured on the VEGF-immobilized substrate, and the mitochondrial activity of the cells was assessed. A calibration curve showing the relation between HUVEC mitochondrial activity and immobilized VEGF density was constructed. Next, immobilized VEGF and VEGF solution were pre-incubated at 37°C, and the pre-incubated VEGF was added to heparin-crosslinked substrate. HUVEC mitochondrial activity declined as the pre-incubation period increased. Density of active immobilized VEGF was derived from HUVEC mitochondrial activity using the calibration curve, and the effect of pre-incubation of VEGF at 37°C was demonstrated quantitatively. Even after culture for 16 days, immobilized VEGF in culture medium at 37°C retained 43%of the initial bioactivity. Immobilized VEGF retained activity better than VEGF solution for at least 12 days of pre-incubation. The present results indicate that immobilization improves the stability of VEGF.

DOI： http://dx.doi.org/10.14326/abe.2.130

Language：English   Publishing type：Research paper (scientific journal)  

Reconstructed liver has been desired as a liver substitute for transplantation. However, reconstruction of a whole liver has not been achieved because construction of a vascular network at an organ scale is very difficult. We focused on decellularized liver (DC-liver) as an artificial scaffold for the construction of a hierarchical vascular network. In this study, we obtained DC-liver and the tubular network structure in which both portal vein and hepatic vein systems remained intact. Furthermore, endothelialization of the tubular structure in DC-liver was achieved, which prevented blood leakage from the tubular structure. In addition, hepatocytes suspended in a collagen sol were injected from the surroundings using a syringe as a suitable procedure for liver cell inoculation. In summary, we developed a base structure consisting of an endothelialized vascular-tree network and hepatocytes for whole liver engineering.

DOI： 10.1016/j.jbiosc.2013.05.020

Language：English   Publishing type：Research paper (scientific journal)  

Tissue engineering requires growth factors, cells and a scaffold to permit effective tissue regeneration. This study focused on the development of a scaffold for liver tissue engineering, because the liver is a central organ for metabolism. We aimed to develop a scaffold to promote expression of liver-specific functions of hepatocytes, with a focus on immobilizing growth factors onto an organ-specific matrix for liver tissue regeneration. Solubilized extracellular matrix from decellularized liver (L-ECM) was obtained following Triton X-100 treatment and consisted of protein and polysaccharide. L-ECM was found to immobilize hepatocyte growth factor (HGF), even in the presence of albumin, with an efficiency of 75%. Additionally, the immobilized HGF on L-ECM film was stably remained in culture condition for 5 days. Immobilized HGF promoted hepatocyte migration, thus indicating that L-ECM-immobilized HGF maintained its native biological activity. Furthermore, L-ECM stimulated the expression of liver-specific functions, including albumin secretion, urea synthesis and ethoxyresorufin-O-deethylase activity, in primary rat hepatocytes cultured in growth factor-free medium. In summary, L-ECM has the potential to become an effective material in the field of regenerative medicine.

DOI： 10.1016/j.jbiosc.2013.05.031

Language：English   Publishing type：Research paper (scientific journal)  

The growth of transplanted hepatocytes is required for the construction of tissue-engineered liver. In this study, cell-embedded hydrogel-filled polyurethane foam plates were subcutaneously transplanted into rat. A liver tissue-like structure was formed by transplanted fetal liver cells in 70% partial hepatectomy treated rat.

DOI： 10.1016/j.jbiosc.2012.11.015

Language：English   Publishing type：Research paper (scientific journal)  

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Language：English   Publishing type：Research paper (scientific journal)  

Poly(vinyl alcohol) (PVA) gel beads crosslinked with sodium phosphate or boric acid have been widely utilized for microorganism immobilization. We previously utilized sodium sulfate to induce crosslinking of PVA for preparing immobilized yeast cells in PVA beads. In this study, we compared the toxicities of sodium sulfate and conventional crosslinkers (sodium phosphate and boric acid) toward Pseudomonas putida F1 (PpF1) and the performance of the corresponding immobilized PpF1 in PVA beads. The toxicity of sodium sulfate to PpF1 was lower than those of the conventional crosslinkers. PVA–sodium sulfate beads showed a higher gel fraction of PVA and a lower swelling ratio in water than PVA–sodium phosphate beads, which indicates that the former had higher stability. PpF1 immobilized in the PVA–sodium sulfate beads completely degraded the pollutant trichloroethylene (TCE) with an initial concentration (0.42 mg/l) within the most common range of TCE concentration found in contaminated field sites.

DOI： 10.1007/s00289-012-0756-4

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3727/096368911X605321

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DOI： 10.1016/j.jbiosc.2011.07.006

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DOI： 10.1016/j.bej.2011.05.010

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DOI： 10.1089/ten.tea.2010.0689

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DOI： 10.1016/j.jbiosc.2009.07.017

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DOI： 10.1016/j.bej.2009.04.002

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DOI： 10.1016/j.bej.2008.12.015

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DOI： 10.1016/j.bej.2008.01.009

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DOI： 10.1158/1535-7163.MCT-05-0227

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DOI： 10.1252/jcej.38.913

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DOI： 10.1263/jbb.100.127

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DOI： 10.1021/bp049600i

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DOI： 10.1002/bit.20329

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DOI： 10.1016/j.bej.2003.09.014

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DOI： 10.1016/j.bej.2003.07.004

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DOI： 10.1252/jcej.37.531

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DOI： 10.1002/bit.20006

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DOI： 10.1016/j.ijpharm.2003.10.014

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DOI： 10.1023/A:1026045503586

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DOI： 10.1080/1024242031000087628

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DOI： 10.3727/000000003783985151

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DOI： 10.1163/156856203322274905

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DOI： 10.1016/S0142-9612(02)00159-X

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DOI： 10.1016/S0376-7388(02)00093-5

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DOI： 10.1016/S0376-7388(01)00731-1

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DOI： 10.1016/S1381-1177(01)00076-5

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DOI： 10.1023/A:1013876313806

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DOI： 10.1067/msy.2002.120118

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DOI： 10.1016/S0142-9612(01)00016-3

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DOI： 10.1016/S1381-1177(01)00007-8

Language：Japanese   Publishing type：Research paper (scientific journal)  

Control of transport characteristic of membrane by multi-layering of polyelectrolyte complex toward microcapsule-shaped bioartificial pancreas

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1046/j.1525-1594.2001.025003194.x

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Catalytic capabilities of lipase immobilized into organically modified silicates by sol-gel method

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (international conference proceedings)  

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DOI： 10.1097/00002480-199909000-00005

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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DOI： 10.1006/jsre.1998.5540

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1023/A:1008040726236

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DOI： 10.1023/A:1008092710307

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DOI： 10.1016/S0928-4931(98)00057-5

Language：English   Publishing type：Research paper (international conference proceedings)  

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Language：English   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Investigation of optimum culture condition for hybrid artificial liver module using PUF/porcine hepatocyte spheroid culture
K. Nakazawa, H. Ijima, M. Kaneko, T. Ito, T. Matsushita, T. Gion, K. Shirabe, M. Shimada, K. Takenaka, K. Sugimachi, K. Funatsu

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1089/ten.1998.4.213

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1163/156856298X00136

Language：English   Publishing type：Research paper (international conference proceedings)  

Publishing type：Research paper (international conference proceedings)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Application of hybrid artificial liver using PUF/hepatocytes-spheroid packed-bed module to warm ischemic liver failure dog
T. Matsushita, S. Koyama, H. Ijima, K. Nakazawa, T. Gion, K. Shirabe, M. Shimada, K. Takenaka, K. Sugimachi, K. Funatsu

Language：Japanese   Publishing type：Research paper (scientific journal)  

Development of drug metabolism simulator using PUF/hepatocyte spheroid culture. -Study of acetaminophen metabolism by hybrid artificial liver system-
K. Nakazawa, H. Mizumoto, H. Ijima, T. Matsushita, K. Funatsu

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (other academic)  

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Publishing type：Research paper (international conference proceedings)  

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Language：English   Publishing type：Research paper (international conference proceedings)  

Language：English   Publishing type：Research paper (scientific journal)  

Responsible for pages：pp.501～550   Language：Japanese   Book type：Scholarly book

Basic Transport Phenomena in Biomedical Engineering (4th Edition) / Bioartificial Organs

Responsible for pages：pp.293～309   Language：Japanese   Book type：Scholarly book

Responsible for pages：pp.113～129   Language：Japanese   Book type：Scholarly book

Responsible for pages：pp.57～64   Language：Japanese   Book type：Scholarly book

Responsible for pages：pp.147～154、監修：岸田晶夫、山岡哲二、干場隆志   Language：Japanese   Book type：Scholarly book

Responsible for pages：pp.3～9   Language：Japanese   Book type：Scholarly book

Language：English   Book type：Scholarly book

Recently, organ construction has been attempted using decellularized organs. In this study, we used decellularized rat liver to construct liver tissue by recellularization. The right lobe of the rat liver was decellularized with 4% Triton X-100 solution, recellularized with 107 rat hepatocytes, and albumin synthesis in the recellularized right lobe was observed. Therefore, we introduce a method of decellularizing rat liver, which retains its fine vascular structure after removal of all the cells, perform organogenesis using the decellularized liver, and evaluate the structural and functional properties of the products.

Responsible for pages：pp.185～226   Language：English   Book type：Scholarly book

Tissue Engineering consists of cells, a scaffold and cytokines. Decellularization represents the removal of cells from tissues or organs. Recently, decellularized tissue has been investigated as a scaffold for tissue engineering, termed decellularized tissue engineering. Importantly, the decellularized organ retains its original structure, which is then used as a template for organ construction. The decellularized organ also retains the tissue-specific extracellular matrix. Therefore, decellularized tissue can be used as a matrix to provide a suitable microenvironment for inoculated cells. Based on these concepts, the reconstruction of tissues/organs with decellularized tissue/organ has been attempted using decellularized tissue engineering. In this chapter, we introduce the typical methods used, history and attainment level for the reconstruction of specific tissues/organs. First, the different decellularized techniques and characteristics are introduced. Then, the commonly used analysis methods and cautionary points during decellularization and reconstruction with decellularized tissues/organs are explained. Next, the specific methods and characteristics of decellularized tissue engineering for specific tissues/organs are introduced. In these sections, the current conditions, problems and future work are explained. Finally, we conclude with a summary of this chapter.

DOI： https://doi.org/10.1007/978-981-10-3328-5_5

Responsible for pages：pp.141～142   Language：Japanese   Book type：Scholarly book

Responsible for pages：pp.309～315   Language：Japanese   Book type：Scholarly book

Responsible for pages：pp.75～80   Language：Japanese   Book type：Scholarly book

Responsible for pages：pp.703～707   Language：Japanese   Book type：Scholarly book

Responsible for pages：pp.85～89   Language：Japanese   Book type：Scholarly book

Responsible for pages：pp.141～147   Language：Japanese   Book type：Scholarly book

Responsible for pages：pp.73-77   Language：Japanese   Book type：Scholarly book

Event date： 2015.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：岡山国際交流センター   Country：Japan  

1. Introduction
Development of a functional tubular construct is important in the field of medical treatment. For example, there is no practical small-diameter artificial blood vessel having 3 mm or less in a diameter. In addition, an artificial bile duct is desired for repair or treatment of stricture of bile duct in the hepato-biliart surgery. We have already reported the development of growth factor immobilizable gelatin1). Therefore, our aim is the development of a functional tubular construct which is replaceable to native tissue by using this functional biomaterial. In this study, we report the development of a functional tubular construct having a suitable mechanical strength for transplantation.
2. Materials and methods
Heparin-collagen conjugate was prepared by using EDC/NHS. Enzymatic cross-linking was used for the gelation of this conjugate2). This conjugate gel had the high affinity with growth factors such as EGF, bFGF, VEGF and HGF, and was able to immobilize these growth factors1). The hydrogel tubes of 1 and 5 mm in internal diameter were prepared as the transplantation samples for rat and pig, respectively.
3. Results and discussion
Endothelial cells on this conjugate gel showed remarkable proliferation and high migration characteristics (Fig.1). These are the characteristics that are extremely effective in a purpose called the promotion of endothelialization. However, the hydrogel tube was too weak for a suture. On the contrary, the mechanical strength of gel tube was much enhanced by woven fabric reinforcement.
This conjugate gel tube was transplanted to rat as the functional portal vein and inferior vena cava. The clot formation occurred immediately in heparin-unconjugated gel tube (control), and blood vessels were occluded. In contrast, the clot formation did not occur during 12-day transplant and maintained the patency well when heparin-gelatin conjugate gel tube was transplanted. In addition, woven fabric reinforced conjugate gel tube (Fig.2) was transplanted as an artificial common bile duct of pig by end-to-end anastomosis.
Therefore, it is expected that woven fabric reinforced functional tubular construct will be a potential scaffold in the field of tissue engineering.
4. Conclusions
Heparin-gelatin conjugate gel tube equipped biocompatibility and growth factor immobilizability. Furthermore, this hydrogel tube prevented blood clotting and enhanced endothelialization. Additionally, sufficient mechanical strength for sutures could be provided by the development of woven fabric reinforcement. Based on this study, transplantable functional hydrogel tube was developed.
Acknowledgement
A part of this study was supported by The NOVARTIS Foundation (Japan) for the Promotion of Science.
References
1) S.Nakamura, T.Kubo, H.Ijima; “Heparin-conjugated gelatin as a growth factor immobilization scaffold,” Journal of Bioscience and Bioengineering, Vol.115, No.5, pp.562-567, 2013
2) H.Ijima, Y-T.Hou, T.Takei: “Development of hepatocyte-embedded hydrogel-filled macroporous scaffold cultures using transglutaminase,” Biochemical Engineering Journal, Vol.52, pp.276-281, 2010

Event date： 2015.9

Language：English   Presentation type：Oral presentation (general)  

Venue：Boston Marriott Copley Place (Boston, MA, U.S.A.)   Country：Korea, Republic of  

Fundamental technology for the creation of whole liver engineering, and functional evaluation of recellularized liver

Event date： 2014.9

Language：English   Presentation type：Oral presentation (general)  

Venue：EXCO (Deagu)   Country：Korea, Republic of  

Fundamental technology for the creation of Whole Liver Engineering

Event date： 2013.5 - 2013.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：九州大学病院　カンファレンスルーム   Country：Japan  

重篤な臓器疾患に対する新たな治療法として再生医工学（Tissue Engineering）に基づく再生医療（Regenerative Medicine）のための技術開発が注目されている。しかしながら、厚みのある組織、特に肝臓のような酸素消費速度の高い臓器の再構築は未だ不可能であり、新たな技術開発が必要である。我々は「細胞」、「増殖因子固定化能を有する機能性ECM」および「血管網構造を有する臓器鋳型」の3要素からなる臓器工学（Whole Organ Engineering）の構築を目指している。これまでに機能性ECMとして、ヘパリン‐コラーゲンコンジュゲートさらには可溶化肝ECMを開発し、これらによる各種増殖因子固定化能、肝特異的機能発現向上さらには移植用基材としての有効性を実証してきた。一方、臓器鋳型については脱細胞化技術に着目し、緻密な血管網を有する肝臓鋳型の取得に成功した。さらに肝細胞および血管内皮細胞を用いた当該鋳型の再細胞化も可能であった。ここでは、これら研究成果について概説するとともに、Whole Liver Engineeringの位置づけと研究開発の現状について議論する。

Event date： 2012.9

Presentation type：Oral presentation (general)  

Venue：東北大学 川内北キャンパス　（仙台市）   Country：Japan  

脱細胞化肝臓と機能性生体材料開発に基づく肝組織工学技術について報告する。さらに、肝臓を対象としてこれまでに行ってきた人工臓器開発ならびに肝組織工学技術開発研究成果を踏まえて肝組織工学の現状と今後の展望についてまとめることで、人工肝臓ならびに肝組織工学それぞれの担うべき役割について考察する。

Event date： 2012.9

Presentation type：Oral presentation (general)  

Venue：Hofburg Congress Center, Vienna   Country：Austria  

Event date： 2012.6

Presentation type：Oral presentation (general)  

Venue：パシフィコ横浜   Country：Japan  

[目的] 代謝の中心である肝臓の組織工学的再構築（Liver Tissue Engineering: LTE）は組織工学領域の中で最も重要かつ困難な課題の一つである。我々は機能性培養基材の開発と血管網を有する臨床スケールのscaffoldの構築により、上記課題の克服を目指している。今回は、細胞包埋機能性ゲル充填多孔質基材（CGS）の皮下移植による肝組織構築に関する研究成果を報告すると共に、実用的LTE技術開発に向けた我々の研究成果をまとめる。[実験方法及び結果] 各種増殖因子が固定化可能な培養基材を開発し、初代肝細胞の組織構築と肝特異的機能発現に対する有効性が得られた。コラーゲンゲルもしくは増殖因子固定化可能なゲルからなるCGSをラットへ皮下移植した場合、分散状態の肝細胞よりも肝細胞スフェロイドを移植することにより移植肝細胞の生存率が向上した。さらに、移植時に部分肝切除術を組み合わせることでその効果は顕著となり、増殖因子固定化可能なゲルからなるCGSの有効性が示された。一方、胎児肝臓細胞を分散状態にてCGSを作製し移植したところ、血管網を有する肝組織様構造体が構築できた。以上のことから、増殖因子固定化可能なゲルからなるCGSはLTE構築に有望であることが示された。

Event date： 2011.12

Presentation type：Oral presentation (general)  

Venue：熊本大学   Country：Japan  

Event date： 2011.11

Presentation type：Oral presentation (general)  

Venue：京都府民総合交流プラザ　京都テルサ   Country：Japan  

Event date： 2011.11

Presentation type：Oral presentation (general)  

Venue：京都府民総合交流プラザ　京都テルサ   Country：Japan  

Event date： 2011.10

Presentation type：Oral presentation (general)  

Venue：九州大学西新プラザ   Country：Japan  

Event date： 2011.10

Presentation type：Oral presentation (general)  

Venue：九州大学西新プラザ   Country：Japan  

Event date： 2011.10

Presentation type：Oral presentation (general)  

Venue：Toyama International Conference Center   Country：Japan  

Event date： 2011.10

Presentation type：Oral presentation (general)  

Venue：Toyama International Conference Center   Country：Japan  

Event date： 2011.10

Presentation type：Oral presentation (general)  

Venue：Toyama International Conference Center   Country：Japan  

Event date： 2011.10

Presentation type：Oral presentation (general)  

Venue：Toyama International Conference Center   Country：Japan  

Event date： 2011.9

Presentation type：Oral presentation (general)  

Venue：東京農工大学   Country：Japan  

Basic Study for Liver Tissue Engineering by Using Decellularized Organ

Event date： 2011.9

Presentation type：Oral presentation (general)  

Venue：名古屋工業大学   Country：Japan  

Event date： 2011.7

Presentation type：Oral presentation (general)  

Venue：北九州国際会議場（福岡）   Country：Japan  

Event date： 2011.7

Presentation type：Oral presentation (general)  

Venue：北九州国際会議場（福岡）   Country：Japan  

Event date： 2011.6

Presentation type：Oral presentation (general)  

Venue：Granada Congress and Exhibition Centre   Country：Spain  

Event date： 2011.6

Presentation type：Oral presentation (general)  

Venue：Granada Congress and Exhibition Centre   Country：Spain  

Event date： 2011.6

Presentation type：Oral presentation (general)  

Venue：Granada Congress and Exhibition Centre   Country：Spain  

Event date： 2011.3

Presentation type：Oral presentation (general)  

Venue：東京農工大学小金井キャンパス、東京   Country：Japan  

Event date： 2011.3

Presentation type：Oral presentation (general)  

Venue：東京農工大学小金井キャンパス、東京   Country：Japan  

Event date： 2011.3

Presentation type：Oral presentation (general)  

Venue：東京農工大学小金井キャンパス、東京   Country：Japan  

Event date： 2011.3

Presentation type：Oral presentation (general)  

Venue：京王プラザホテル、東京   Country：Japan  

Event date： 2011.1

Presentation type：Oral presentation (general)  

Venue：九州大学馬出キャンパス、福岡   Country：Japan  

Cell-embedded functional gel-filled scaffold culture for liver tissue engineering
Hiroyuki Ijima, Nana Shirakigawa, Yung-Te Hou, Shintaro Nakamura, Takayuki Takei, Koei Kawakami

Event date： 2010.12

Presentation type：Oral presentation (general)  

Venue：the Hilton in the Walt Disney World Resort, Orlando   Country：United States  

Event date： 2010.12

Presentation type：Oral presentation (general)  

Venue：the Hilton in the Walt Disney World Resort, Orlando   Country：United States  

Event date： 2010.11

Presentation type：Oral presentation (general)  

Venue：グランドプリンスホテル広島   Country：Japan  

Event date： 2010.11

Presentation type：Oral presentation (general)  

Venue：グランドプリンスホテル広島   Country：Japan  

Event date： 2010.10

Presentation type：Oral presentation (general)  

Venue：徳島大学   Country：Japan  

Event date： 2010.10

Presentation type：Oral presentation (general)  

Venue：徳島大学   Country：Japan  

Event date： 2010.9

Presentation type：Oral presentation (general)  

Venue：同志社大学   Country：Japan  

Event date： 2010.9

Presentation type：Oral presentation (general)  

Venue：Hokkaido University   Country：Japan  

Event date： 2010.7

Presentation type：Oral presentation (general)  

Venue：北九州国際会議場   Country：Japan  

Event date： 2010.3

Presentation type：Oral presentation (general)  

Venue：鹿児島大学   Country：Japan  

Event date： 2010.3

Presentation type：Oral presentation (general)  

Venue：広島国際会議場   Country：Japan  

Event date： 2009.10

Presentation type：Oral presentation (general)  

Venue：西日本総合展示場（北九州市）   Country：Japan  

Event date： 2009.9

Presentation type：Oral presentation (general)  

Venue：名古屋大学   Country：Japan  

Event date： 2009.9

Presentation type：Oral presentation (general)  

Venue：広島大学   Country：Japan  

Event date： 2009.9

Presentation type：Oral presentation (general)  

Venue：広島大学   Country：Japan  

Event date： 2009.8 - 2009.9

Presentation type：Oral presentation (general)  

Venue：Seoul   Country：Korea, Republic of  

Event date： 2009.3

Presentation type：Oral presentation (general)  

Venue：東京国際フォーラム   Country：Japan  

Organoid formation and the function expression of primary rat hepatocytes are improved by culturing with hepatocyte growth factor-immobilized culture substratum

Event date： 2008.11

Presentation type：Oral presentation (general)  

Venue：ホテル日航姫路（兵庫県姫路市）   Country：Japan  

Event date： 2008.5 - 2008.6

Presentation type：Oral presentation (general)  

Venue：Amsterdam RAI   Country：Netherlands  

Event date： 1996.5

Presentation type：Oral presentation (general)  

Venue：Faro   Country：Portugal  

Presentation type：Oral presentation (general)  

Venue：Amsterdam RAI   Country：Netherlands  

Presentation type：Oral presentation (general)  

Venue：Grand Prince Hotel Akasaka   Country：Japan  

Presentation type：Oral presentation (general)  

Venue：名古屋国際会議場   Country：Japan  

Presentation type：Oral presentation (general)  

Venue：九州大学伊都キャンパス   Country：Japan  

Event date： 2024.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：九州大学西新プラザ   Country：Japan  

Event date： 2024.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：朱鷺メッセ 新潟コンベンションセンター、ホテル日航新潟   Country：Japan  

Event date： 2024.3

Language：English   Presentation type：Oral presentation (general)  

Venue：朱鷺メッセ 新潟コンベンションセンター、ホテル日航新潟   Country：Japan  

Event date： 2024.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：大阪公立大学 中百舌鳥キャンパス   Country：Japan  

Event date： 2024.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：大阪公立大学 中百舌鳥キャンパス   Country：Japan  

Event date： 2024.1

Language：Japanese  

Venue：九州大学 医学部 百年講堂   Country：Japan  

Event date： 2023.12

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：北九州市立大学　ひびきのキャンパス   Country：Japan  

Event date： 2023.12

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：北九州市立大学　ひびきのキャンパス   Country：Japan  

Event date： 2023.12

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：九州大学 馬出キャンパス   Country：Japan  

Event date： 2023.12

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：九州大学 馬出キャンパス   Country：Japan  

Event date： 2023.11

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：九州大学 椎木講堂   Country：Japan  

Event date： 2023.11

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：ホテル　イースト２１東京   Country：Japan  

Event date： 2023.11

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：ホテル　イースト２１東京   Country：Japan  

Event date： 2023.10

Language：English   Presentation type：Oral presentation (general)  

Venue：National Taiwan University   Country：Taiwan, Province of China  

[Introduction] Functional replacement using artificial organs has been used for a long time to treat severe organ disorders that are difficult to rescue and cure through medical and surgical treatment. Since, liver is a central organ for metabolism in our body, liver transplantation is the only effective therapy for severe liver failure patients. However, serious donor shortage remains a difficult problem to solve. Therefore, the development of effective liver support system using functional liver cells is expected.

[Artificial liver] In my laboratory, research is being carried out on the development of various bioartificial livers, as represented by (1) to (3) below. (1) A practical high-performance hybrid artificial liver support system (HALSS) consisting of a high-performance “hybrid artificial liver module and a “blood extracorporeal circulation system” has been developed. Furthermore, the effectiveness of this HALSS was demonstrated in preclinical animal experiments using pigs with severe liver failure. The significance of HALSS is “bridge use until transplantation” and “treatment of liver failure and induction of liver regeneration”. (2) Organoid transplantation technology based on functional ECM, including organ-specific ECM, have been developed. Functional ECM, which has the ability to immobilize growth factors associated with liver regeneration, has successfully formed functional liver tissue accompanied by angiogenesis in vivo. Since such functional organoid transplantation does not require special techniques or systems, it is expected to become a highly versatile and practical artificial liver. (3) A whole organ engineered (WOE) liver graft was developed by optimizing liver decellularization, cell seeding into the decellularized liver, and organ culture system. This WOE-liver graft was shown to be effective in curing and saving lives in animals with liver failure.

[Shaping of functional materials] Functional materials developed in artificial liver research are shaped into nanostructures and used in various medical engineering fields.
Electrospun nanofiber : (Organoid-laden patch) Electrospinning of liver-specific ECM yielded nanofibrous nonwoven fabrics with fiber diameters around 600 nm, which promoted organoid formation of hepatocytes. This organoid-laden nanofiber nonwoven fabric could be used as a new functional culture system and even be directly implanted as a patch onto the liver surface. (Wound dressing) Nanofibrous nonwoven fabrics made of heparinized gelatin (Hep-Gel) were effective in promoting normal skin tissue regeneration, reducing inflammatory responses, and inhibiting scar formation. These have achieved excellent wound healing promoting effects in animal models of skin defects and pressure ulcers. This was due to the induction of synergistic effects of exogenous and endogenous growth factors by Hep-Gel nanofibers. (Nerve guidance conduits) Nerve guidance conduits consisting of an “electrospun tube” with a core material of “aligned electrospun nanofibers made of Hep-Gel” have been developed. This conduit, which was transplanted into animals with sciatic nerve defects, promoted the induction of nerve regeneration while suppressing cell infiltration from the surrounding area.
Nanogel dispersion : (Transdermal drug delivery) A W/O type nanogel dispersion (G/O) consisting of Hep-Gel was developed. This G/O was excellent in stable retention of biopharmaceuticals, particle stability, transdermal permeability, and sustained release of encapsulated drugs. G/O was effective in inducing subcutaneous angiogenesis, inhibiting damage caused by UVB, and promoting healing of the damage. (Anticancer drugs) O/W type nanogel dispersion (G/W) was developed. G/W containing an anticancer drug, which was administered into the tail vein of cancer-bearing mice, showed excellent anticancer activity. (Eye drops) G/W with a particle size of 150-200 nm achieved drug delivery to the retina and sustained release of the encapsulated drug. This result raises expectations that “treatment using eye drops for posterior eye diseases such as age-related macular degeneration” will become a reality.

[Conclusion] The development of various artificial livers and their therapeutic and life-saving effects on animals with liver failure have been demonstrated. This allows for custom-made liver failure treatments. On the other hand, it has become clear that the functional materials developed in the above research are effective for development in various medical engineering fields by shaping them into nanostructures.

Event date： 2023.9

Language：English   Presentation type：Oral presentation (general)  

Venue：福岡大学   Country：Japan  

Event date： 2023.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡大学   Country：Japan  

Event date： 2023.9

Language：English   Presentation type：Oral presentation (general)  

Venue：福岡大学   Country：Japan  

Event date： 2023.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡大学   Country：Japan  

Event date： 2023.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡大学   Country：Japan  

Event date： 2023.8

Language：Others  

Venue：オンライン   Country：Japan  

Development of eye drops carrier for retinal diseases using tissue permeable nanogel emulsion

Event date： 2023.7

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：北九州国際会議場   Country：Japan  

Event date： 2023.7

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：北九州国際会議場   Country：Japan  

Event date： 2023.7

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：北九州国際会議場   Country：Japan  

Event date： 2023.7

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：北九州国際会議場   Country：Japan  

Event date： 2023.7

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：北九州国際会議場   Country：Japan  

Event date： 2023.7

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：北九州国際会議場   Country：Japan  

Event date： 2023.5

Language：English   Presentation type：Oral presentation (general)  

Venue：Suzhou International Expo Center, Suzhou   Country：China  

Objective：
Nerve injuries cause huge discomfort severely affecting the life quality. Traditionally, autograftsare used as nerve conduits. Nevertheless, shortage of donors restrict their wide applicability.Artificial nerve guidance conduits (NGCs) based on polymeric biomaterials may overcomeabovementioned limitations. The objective of this research was to design NGCs based onpolycaprolactone/gelatin (PCL/Gel)-based aligned electrospun fibers. Heparin and brain-deriveddecellularized extracellular matrix (B-ECM) were used to impart bioactivity and growth factors(GFs) immobilizability.
Methods：
B-ECM was prepared by decellularization. PCL/Gel or PCL/Gel-B-ECM based core/shell typealigned fibers were fabricated by electrospinning. PCL/Gel fibers were modified with heparin toimmobilize basic fibroblast growth factor (bFGF) and nerve growth factor (NGF). B-ECM contentas well as fibers' morphology were varied to steer their influences on Schwann cells and PC12cells. To impede the infiltration of inflammatory cells, tubular PCL/Gel scaffolds were prepared.NGCs were fabricated by using aligned fibers and tubular scaffolds. NGCs were transplantedinto sciatic nerve defect models in rats. Histological and immunohistochemical analyzes wereperformed to discern nerve repair.
Results：
Morphological analysis revealed the formation of aligned fibers, while TEM displayed core shellstructures of PCL/Gel and PCL/Gel-B-ECM fibers. Heparinized PCL/Gel fibers affordedimmobilization and retention of bFGF and NGF. Similarly, B-ECM enabled sequestration ofendogenous and exogenous NGF. Heparinized and B-ECM modeled fibers as well as alignedmorphology promoted an alignment of Schwann cells and neurites outgrowth of PC12 cells. In vitro and in vivo tests showed diffusion and transport of bovine serum albumin (BSA) while a minimal infiltration of host cell types from the graft wall of tubular scaffolds, respectively. NGCsshowed good suturability, biocompatibility, structural stability, and neo-tissue formation in vivo.
Conclusion：
Heparin-immobilized and B-ECM modeled aligned electrospun fibers may offer a promisingplatform to improve nerve repair by influencing neurites outgrowth, promotingretention/sequestration of growth factors, and modulating inflammatory response.
Key words：
Nerve guidance conduits, electrospinning, neural engineering, heparin, growthfactors, aligned fibers, tissue engineering

Other Link： https://apcmbe.sciconf.cn/cn/web/index/14683_1296363__

Event date： 2023.5

Language：English   Presentation type：Oral presentation (general)  

Venue：Suzhou International Expo Center, Suzhou   Country：China  

Objective：
Functional loss of cells, tissues, or organs due to trauma, injury, or other diseases causes enormous complications. Cell-based therapies offer promising options; however, intensive in vitro cell manipulations may hinder this approach. Intelligent multifunctional polymeric biomaterials offer an alternative paradigm to orchestrate host’s own reparative responses by inducing/recruiting endogenous stem cells and progenitor cells. The objective of this research was to design intelligent multifunctional biomaterials platforms for in situ (cell-free) regeneration of different types of tissues, including blood vessels, heart, nerves, skin, patellar tendon, and bone/cartilage.
Methods：
Cytokines and chemokines, such as substance P (SP), stromal cell-derived factor-1 alpha (SDF-1α), vascular endothelial growth factor (VEGF), and MSC-affinity peptide were incorporated into biomaterials either by tethering with polymers in bulk or by encapsulation. Cytocompatibility, hemocompatibility, cell migration, and drug/GFs release were studied. In vivo evaluations were performed in different animal models, like abdominal aorta, sciatic nerve defect, patellar tendon; excisional defects. Explants were analyzed by histological and immuno-histochemical assays.
Results：
Modified biomaterials afforded spatio-temporal release of bioactive cues as well as showed good cell mobilization and recruitment, hemocompatibility, cytocompatibility, and GFs sequestration/retention in vitro. Explanted materials showed superior effect of instructive biomaterials for the in situ regeneration of different types of tissues, including blood vessel, nerves, bone/cartilage, patellar tendon, skin, and infarcted myocardium than that of unmodified materials. Host stem/progenitor cells were recruited into bioactivated polymers either from the bone marrow (BM), peripheral circulation, or from the surrounding tissues and were found to be differentiated into targeted cell types, including CD31+ endothelial cells (ECs) and alpha smooth muscle actin (α-SMA)-positive smooth muscle cells.
Conclusion：
Taken together, instructive polymeric biomaterials may promote in situ tissue repair through an endogenous mobilization and recruitment of host stem/pronator cells, which may have great application prospect for regnerative medicine and tissue engineering (TE) as well as related disciplines.
Key words ： In situ tissue repair, nerve regeneration, vascular grafts, cytokines/chemokines, wound healing, cytokines and chemokines, tissue engineering, biomaterials

Other Link： https://apcmbe.sciconf.cn/cn/web/index/14683_1296363__

Event date： 2023.3

Language：English   Presentation type：Oral presentation (general)  

Venue：国立京都国際会館   Country：Japan  

Event date： 2023.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：国立京都国際会館   Country：Japan  

Event date： 2023.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：国立京都国際会館   Country：Japan  

Event date： 2023.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：国立京都国際会館   Country：Japan  

Event date： 2023.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：国立京都国際会館   Country：Japan  

Event date： 2023.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：東京農工大学 小金井キャンパス   Country：Japan  

Event date： 2023.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：東京農工大学 小金井キャンパス   Country：Japan  

Event date： 2023.2

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：九州大学医学部百年講堂   Country：Japan  

Event date： 2023.2

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：九州大学医学部百年講堂   Country：Japan  

Event date： 2022.12

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：熊本大学 薬学部 宮本記念館   Country：Japan  

Event date： 2022.12

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：佐賀大学   Country：Japan  

Event date： 2022.12

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：佐賀大学   Country：Japan  

Event date： 2022.11

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：名護屋国際会議場   Country：Japan  

Estimation of effect of tobacco smoke exposure on the eye and the lacrimal gland of guinea pig

Event date： 2022.11

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：愛媛県県民文化会館   Country：Japan  

Event date： 2022.10

Language：English   Presentation type：Oral presentation (general)  

Venue：オンライン   Country：Japan  

Event date： 2022.10

Language：English   Presentation type：Oral presentation (general)  

Venue：ICC Jeju   Country：Korea, Republic of  

Growth factor-immobilized heparinized Vascular Patches Composed of Electrospun Polycaprolactone/Decellularized extracellular matrix (PCL/dECM) nanofibers

Event date： 2022.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：信州大学（長野キャンパス／オンライン）   Country：Japan  

Event date： 2022.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：信州大学（長野キャンパス／オンライン）   Country：Japan  

Event date： 2022.7

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：北九州国際会議場   Country：Japan  

Event date： 2022.7

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：北九州国際会議場   Country：Japan  

Event date： 2022.7

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：北九州国際会議場   Country：Japan  

Event date： 2022.7

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：北九州国際会議場   Country：Japan  

Event date： 2022.7

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：北九州国際会議場   Country：Japan  

Event date： 2022.7

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：北九州国際会議場   Country：Japan  

Event date： 2022.6

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡国際会議場   Country：Japan  

Development of nanogel emulsion for drug delivery to posterior eye segment
Higuchi Akihiro, Doi Ryota, Inoue Yuta, Zhang Yi, Ijima Hiroyuki

Event date： 2021.12

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：Web形式（Zoom）   Country：Japan  

Medical engineering deployment based on ECM-mimetic material and its shaping

Event date： 2021.12

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：Web形式（Zoom）   Country：Japan  

Development of nervous ECM nanofibers and research for peripheral nerve regeneration

Event date： 2021.12

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：Web形式（Zoom）   Country：Japan  

New technology of Gel-in-Oil emulsion delivery for inducing angiogenesis

Event date： 2021.12

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：Zoom によるオンライン形式   Country：Japan  

Event date： 2021.11

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：名古屋国際会議場（口頭発表）、オンライン（ポスター発表）   Country：Japan  

Fabrication of bile excretion system by co-culturing hepatocyte spheroids with bile duct-like tissue

Event date： 2021.11

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：名古屋国際会議場（口頭発表）、オンライン（ポスター発表）   Country：Japan  

Development of a smart folding and expanding cell sheet delivery device

Event date： 2021.11

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：ハイブリッド形式（神戸コンベンションセンター）   Country：Japan  

Event date： 2021.11

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：Web開催   Country：Japan  

Effect of tobacco smoke exposure on the visual function

Event date： 2021.10

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン   Country：Japan  

A new technology of bFGF-contained Gel-in-Oil emulsion delivery for inducing angiogenesis

Event date： 2021.10

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン   Country：Japan  

Cyst formation from chinese hamster kidney-derived stem cells using organ specific ECM gel

Event date： 2021.7

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン開催   Country：Japan  

Event date： 2021.7

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン開催   Country：Japan  

Event date： 2021.7

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン開催   Country：Japan  

Event date： 2021.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン開催   Country：Japan  

Event date： 2021.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン開催   Country：Japan  

Event date： 2021.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン開催   Country：Japan  

Event date： 2021.1

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン開催   Country：Japan  

Event date： 2021.1

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン開催   Country：Japan  

Event date： 2020.12

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン開催   Country：Japan  

Event date： 2020.12

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン開催   Country：Japan  

Event date： 2020.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン開催   Country：Japan  

Event date： 2020.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン開催   Country：Japan  

Event date： 2020.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン開催   Country：Japan  

Event date： 2020.5

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：パシフィコ横浜⇒web開催   Country：Japan  

Event date： 2020.5

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：パシフィコ横浜⇒web開催   Country：Japan  

Event date： 2020.5

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：パシフィコ横浜⇒web開催   Country：Japan  

Event date： 2020.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：関西大学   Country：Japan  

Event date： 2020.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：関西大学   Country：Japan  

Event date： 2020.1

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：ＫＫＲホテル熊本   Country：Japan  

Event date： 2020.1

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：ＫＫＲホテル熊本   Country：Japan  

Event date： 2019.12

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：九州大学 西新プラザ   Country：Japan