Peripheral nerve injuries(PNIs)affect approximately one million people globally every year.While autologous nerve transplantation remains the gold standard for healing PNIs with large gaps,limitations such as donor si...Peripheral nerve injuries(PNIs)affect approximately one million people globally every year.While autologous nerve transplantation remains the gold standard for healing PNIs with large gaps,limitations such as donor site morbidity and limited nerve availability present challenges in clinical application,highlighting the need for innovative solutions based on synthetic biomaterials.In this study,we explored a composite nerve conduit that combines a poly(lactic-co-glycolic acid)(PLGA)shell and a decellularized extracellular matrix(dECM)seeded with Schwann cells(SCs).In particular,the dECM,derived from rat sciatic nerves,retains the native tissue structure and bioactive components.In vitro studies showed that SC-seeded dECM promotes cell viability,proliferation,and alignment.In vivo testing using a rat sciatic nerve defect model demonstrated that the PLGA/dECM-SC conduit significantly improved nerve regeneration compared with conduits without SCs,showing enhanced axonal growth,myelination,and motor function restoration comparable to autografts.This approach offers a promising alternative to autologous nerve grafts in the clinical treatment of PNIs.展开更多
Articular cartilage has a limited self-healing capacity,leading to joint degeneration and osteoarthritis over time.Therefore,bioactive scaffolds are gaining attention as a promising approach to regenerating and repair...Articular cartilage has a limited self-healing capacity,leading to joint degeneration and osteoarthritis over time.Therefore,bioactive scaffolds are gaining attention as a promising approach to regenerating and repairing damaged articular cartilage through tissue engineering.In this study,we reported on a novel 3D bio-printed proteinaceous bioactive scaffolds combined with natural porcine cancellous bone dECM,tempo-oxidized cellulose nanofiber(TOCN),and alginate carriers for TGF-β1,FGF-18,and ADSCs to repair cartilage defects.The characterization results demonstrate that the 3D scaffolds are physically stable and facilitate a controlled dual release of TGF-β1 and FGF-18.Moreover,the key biological proteins within the bioactive scaffold actively interact with the biological systems to create a favorable microenvironment for cartilage regeneration.Importantly,the in vitro,in vivo,and in silico simulation showed that the scaffolds promote stem cell recruitment,migration,proliferation,and ECM deposition,and synergistic effects of TGF-β1/FGF-18 with the bioactive scaffolds significantly regulate stem cell chondrogenesis by activating the PI3K/AKT and TGFβ1/Smad4 signaling pathways.After implantation,the proteinaceous bioactive scaffold led to the regeneration of mechanically robust,full-thickness cartilage tissue that closely resembles native cartilage.Thus,these findings may provide a promising approach for regulating stem cell chondrogenesis and treating in situ cartilage regeneration.展开更多
Ischemic cardiomyopathy(ICM)affect millions of patients globally.Decellularized extracellular matrix materials(dECM)have components,microstructure and mechanical properties similar to healthy cardiac tissues,and can b...Ischemic cardiomyopathy(ICM)affect millions of patients globally.Decellularized extracellular matrix materials(dECM)have components,microstructure and mechanical properties similar to healthy cardiac tissues,and can be manufactured into various forms of implantable biomaterials including injectable hydrogels or epicardial patches,which have been extensively reported to attenuate pathological left ventricular remodeling and maintain heart function.Recently,dECM medical devices for ICM treatment have been approved for clinical use or studied in clinical trials,exhibiting considerable translation potential.Cells,growth factors and other bioactive agents have been incorporated with different dECM materials to improve the therapeutic outcomes.In addition,more detailed aspects of the biological effects and mechanisms of dECM treatment are being revealed.This review summarized recent advances in dECM materials from variable sources for cardiac repair,including extraction of extracellular matrix,cell integration,smart manufacturing of injectable hydrogels and cardiac patch materials,and their therapeutic applications.Besides,this review provides an outlook on the cutting-edge development directions in the field.展开更多
Cartilage injuries are common problems that increase with the population aging.Cartilage is an avascular tissue with a relatively low level of cellular mitotic activity,which makes it impossible to heal spontaneously....Cartilage injuries are common problems that increase with the population aging.Cartilage is an avascular tissue with a relatively low level of cellular mitotic activity,which makes it impossible to heal spontaneously.To compensate for this problem,three-dimensional bio-printing has attracted a great deal of attention in cartilage tissue engineering.This emerging technology aims to create three-dimensional functional scaffolds by accurately depositing layer-by-layer bio-inks composed of biomaterial and cells.As a novel bio-ink,a decellularized extracellular matrix can serve as an appropriate substrate that contains all the necessary biological cues for cellular interactions.Here,this review is intended to provide an overview of decellularized extracellular matrix-based bio-inks and their properties,sources,and preparation process.Following this,decellularized extracellular matrix-based bio-inks for cartilage tissue engineering are discussed,emphasizing cell behavior and in-vivo applications.Afterward,the current challenges and future outlook will be discussed to determine the conclusing remarks.展开更多
基金support provided by the Ningbo Natural Science Foundation(No.2023J137)the Natural Science Foundation of Zhejiang Province(No.BY23H180015)the Zhejiang Medical Science and Technology Project(Nos.2022KY1101 and 2022KY111).
文摘Peripheral nerve injuries(PNIs)affect approximately one million people globally every year.While autologous nerve transplantation remains the gold standard for healing PNIs with large gaps,limitations such as donor site morbidity and limited nerve availability present challenges in clinical application,highlighting the need for innovative solutions based on synthetic biomaterials.In this study,we explored a composite nerve conduit that combines a poly(lactic-co-glycolic acid)(PLGA)shell and a decellularized extracellular matrix(dECM)seeded with Schwann cells(SCs).In particular,the dECM,derived from rat sciatic nerves,retains the native tissue structure and bioactive components.In vitro studies showed that SC-seeded dECM promotes cell viability,proliferation,and alignment.In vivo testing using a rat sciatic nerve defect model demonstrated that the PLGA/dECM-SC conduit significantly improved nerve regeneration compared with conduits without SCs,showing enhanced axonal growth,myelination,and motor function restoration comparable to autografts.This approach offers a promising alternative to autologous nerve grafts in the clinical treatment of PNIs.
基金supported by the Basic Science Research Program through the National Research Foundation(NRF),funded by the Ministry of Education,Republic of Korea(2015R1A6A1A03032522)Technology Development Program(RS-2023-00281111)funded by the Ministry of SMEs and Startups(MSS,Korea)and partially funded by the Soonchunhyang University,Republic of Korea.
文摘Articular cartilage has a limited self-healing capacity,leading to joint degeneration and osteoarthritis over time.Therefore,bioactive scaffolds are gaining attention as a promising approach to regenerating and repairing damaged articular cartilage through tissue engineering.In this study,we reported on a novel 3D bio-printed proteinaceous bioactive scaffolds combined with natural porcine cancellous bone dECM,tempo-oxidized cellulose nanofiber(TOCN),and alginate carriers for TGF-β1,FGF-18,and ADSCs to repair cartilage defects.The characterization results demonstrate that the 3D scaffolds are physically stable and facilitate a controlled dual release of TGF-β1 and FGF-18.Moreover,the key biological proteins within the bioactive scaffold actively interact with the biological systems to create a favorable microenvironment for cartilage regeneration.Importantly,the in vitro,in vivo,and in silico simulation showed that the scaffolds promote stem cell recruitment,migration,proliferation,and ECM deposition,and synergistic effects of TGF-β1/FGF-18 with the bioactive scaffolds significantly regulate stem cell chondrogenesis by activating the PI3K/AKT and TGFβ1/Smad4 signaling pathways.After implantation,the proteinaceous bioactive scaffold led to the regeneration of mechanically robust,full-thickness cartilage tissue that closely resembles native cartilage.Thus,these findings may provide a promising approach for regulating stem cell chondrogenesis and treating in situ cartilage regeneration.
基金supported by the National Key Research and Development Program of China(no.2019YFE0117400)National Natural Science Foundation of China(no.82202328)Fundamental Research Funds for the Central Universities(226-2023-00066).
文摘Ischemic cardiomyopathy(ICM)affect millions of patients globally.Decellularized extracellular matrix materials(dECM)have components,microstructure and mechanical properties similar to healthy cardiac tissues,and can be manufactured into various forms of implantable biomaterials including injectable hydrogels or epicardial patches,which have been extensively reported to attenuate pathological left ventricular remodeling and maintain heart function.Recently,dECM medical devices for ICM treatment have been approved for clinical use or studied in clinical trials,exhibiting considerable translation potential.Cells,growth factors and other bioactive agents have been incorporated with different dECM materials to improve the therapeutic outcomes.In addition,more detailed aspects of the biological effects and mechanisms of dECM treatment are being revealed.This review summarized recent advances in dECM materials from variable sources for cardiac repair,including extraction of extracellular matrix,cell integration,smart manufacturing of injectable hydrogels and cardiac patch materials,and their therapeutic applications.Besides,this review provides an outlook on the cutting-edge development directions in the field.
基金The work was supperted by the Alexander von Humboldt foundation(to FG).
文摘Cartilage injuries are common problems that increase with the population aging.Cartilage is an avascular tissue with a relatively low level of cellular mitotic activity,which makes it impossible to heal spontaneously.To compensate for this problem,three-dimensional bio-printing has attracted a great deal of attention in cartilage tissue engineering.This emerging technology aims to create three-dimensional functional scaffolds by accurately depositing layer-by-layer bio-inks composed of biomaterial and cells.As a novel bio-ink,a decellularized extracellular matrix can serve as an appropriate substrate that contains all the necessary biological cues for cellular interactions.Here,this review is intended to provide an overview of decellularized extracellular matrix-based bio-inks and their properties,sources,and preparation process.Following this,decellularized extracellular matrix-based bio-inks for cartilage tissue engineering are discussed,emphasizing cell behavior and in-vivo applications.Afterward,the current challenges and future outlook will be discussed to determine the conclusing remarks.