Axon regeneration and remyelination of the damaged region is the most common repair strategy for spinal cord injury.However,achieving good outcome remains difficult.Our previous study showed that porcine decellularize...Axon regeneration and remyelination of the damaged region is the most common repair strategy for spinal cord injury.However,achieving good outcome remains difficult.Our previous study showed that porcine decellularized optic nerve better mimics the extracellular matrix of the embryonic porcine optic nerve and promotes the directional growth of dorsal root ganglion neurites.However,it has not been reported whether this material promotes axonal regeneration in vivo.In the present study,a porcine decellularized optic nerve was seeded with neurotrophin-3-overexpressing Schwann cells.This functional scaffold promoted the directional growth and remyelination of regenerating axons.In vitro,the porcine decellularized optic nerve contained many straight,longitudinal channels with a uniform distribution,and microscopic pores were present in the channel wall.The spatial micro topological structure and extracellular matrix were conducive to the adhesion,survival and migration of neural stem cells.The scaffold promoted the directional growth of dorsal root ganglion neurites,and showed strong potential for myelin regeneration.Furthermore,we transplanted the porcine decellularized optic nerve containing neurotrophin-3-overexpressing Schwann cells in a rat model of T10 spinal cord defect in vivo.Four weeks later,the regenerating axons grew straight,the myelin sheath in the injured/transplanted area recovered its structure,and simultaneously,the number of inflammatory cells and the expression of chondroitin sulfate proteoglycans were reduced.Together,these findings suggest that porcine decellularized optic nerve loaded with Schwann cells overexpressing neurotrophin-3 promotes the directional growth of regenerating spinal cord axons as well as myelin regeneration.All procedures involving animals were conducted in accordance with the ethical standards of the Institutional Animal Care and Use Committee of Sun Yat-sen University(approval No.SYSU-IACUC-2019-B034)on February 28,2019.展开更多
Neuropathologies include the deterioration and damage of the nervous system,especially neurons present in the brain,spinal cord and peripheral nervous system.Damage or alternations in neurons makes their structure and...Neuropathologies include the deterioration and damage of the nervous system,especially neurons present in the brain,spinal cord and peripheral nervous system.Damage or alternations in neurons makes their structure and functionality abnormal.Every year over 90,000 people get affected by neurodegenerative diseases in the USA.Among all the neurological pathologies,展开更多
Porous titanium(Ti)scaffolds have been extensively utilized as bone substitute scaffolds due to their superior biocompatibility and excellent mechanical properties.However,naturally formed TiO2 on the surface limits f...Porous titanium(Ti)scaffolds have been extensively utilized as bone substitute scaffolds due to their superior biocompatibility and excellent mechanical properties.However,naturally formed TiO2 on the surface limits fast osseointegration.Different biomolecules have been widely utilized to overcome this issue;however,homogeneous porous Ti scaffolds could not simultaneously deliver multiple biomolecules that have different release behaviors.In this study,functionally graded porous Ti scaffolds(FGPTs)with dense inner and porous outer parts were fabricated using a two-body combination and densification procedure.FGPTs with growth factor(BMP-2)and antibiotics(TCH)exhibited suitable mechanical properties as bone substituting material and presented good structural stability.The release of BMP-2 was considerably prolonged,whereas the release of TCH was comparable to that of homogenous porous titanium scaffolds(control group).The osteogenic differentiation obtained using FGPTs was maintained due to the prolonged release of BMP-2.The antimicrobial properties of these scaffolds were verified using S.aureus in terms of prior release time.In addition,various candidates for graded porous Ti scaffolds with altered pore characteristics were presented.展开更多
Nerve diseases including acute injury such as peripheral nerve injury(PNI),spinal cord injury(SCI)and traumatic brain injury(TBI),and chronic disease like neurodegeneration disease can cause various function disorders...Nerve diseases including acute injury such as peripheral nerve injury(PNI),spinal cord injury(SCI)and traumatic brain injury(TBI),and chronic disease like neurodegeneration disease can cause various function disorders of nervous system,such as those relating to memory and voluntary movement.These nerve diseases produce great burden for individual families and the society,for which a lot of efforts have been made.Axonal pathways represent a unidirectional and aligned architecture allowing systematic axonal development within the tissue.Following a traumatic injury,the intricate architecture suffers disruption leading to inhibition of growth and loss of guidance.Due to limited capacity of the body to regenerate axonal pathways,it is desirable to have biomimetic approach that has the capacity to graft a bridge across the lesion while providing optimal mechanical and biochemical cues for tissue regeneration.And for central nervous system injury,one more extra precondition is compulsory:creating a less inhibitory surrounding for axonal growth.Electrospinning is a cost-effective and straightforward technique to fabricate extracellular matrix(ECM)-like nanofibrous structures,with various fibrous forms such as random fibers,aligned fibers,3D fibrous scaffold and core-shell fibers from a variety of polymers.The diversity and versatility of electrospinning technique,together with functionalizing cues such as neurotrophins,ECM-based proteins and conductive polymers,have gained considerable success for the nerve tissue applications.We are convinced that in the future the stem cell therapy with the support of functionalized electrospun nerve scaffolds could be a promising therapy to cure nerve diseases.展开更多
Lacking self-repair abilities,injuries to articular cartilage can lead to cartilage degeneration and ultimately result in osteoarthritis.Tissue engineering based on functional bioactive scaffolds are emerging as promi...Lacking self-repair abilities,injuries to articular cartilage can lead to cartilage degeneration and ultimately result in osteoarthritis.Tissue engineering based on functional bioactive scaffolds are emerging as promising approaches for articular cartilage regeneration and repair.Although the use of cell-laden scaffolds prior to implantation can regenerate and repair cartilage lesions to some extent,these approaches are still restricted by limited cell sources,excessive costs,risks of disease transmission and complex manufacturing practices.Acellular approaches through the recruitment of endogenous cells offer great promise for in situ articular cartilage regeneration.In this study,we propose an endogenous stem cell recruitment strategy for cartilage repair.Based on an injectable,adhesive and self-healable o-alg-THAM/gel hydrogel system as scaffolds and a biophysio-enhanced bioactive microspheres engineered based on hBMSCs secretion during chondrogenic differentiation as bioactive supplement,the as proposed functional material effectively and specifically recruit endogenous stem cells for cartilage repair,providing new insights into in situ articular cartilage regeneration.展开更多
基金supported by grants from the National Key R&D Program of China,No.2017YFA0104704(to BQL)the Young Elite Scientist Sponsorship Program(YESS)by China Association for Science and Technology(CAST),No.2018QNRC001(to BQL)+1 种基金the Fundamental Research Funds for the Central Universities,China,No.18ykpy38(to BQL)the National Natural Science Foundation of China,Nos.81971157(to BQL),81891003(to YSZ).
文摘Axon regeneration and remyelination of the damaged region is the most common repair strategy for spinal cord injury.However,achieving good outcome remains difficult.Our previous study showed that porcine decellularized optic nerve better mimics the extracellular matrix of the embryonic porcine optic nerve and promotes the directional growth of dorsal root ganglion neurites.However,it has not been reported whether this material promotes axonal regeneration in vivo.In the present study,a porcine decellularized optic nerve was seeded with neurotrophin-3-overexpressing Schwann cells.This functional scaffold promoted the directional growth and remyelination of regenerating axons.In vitro,the porcine decellularized optic nerve contained many straight,longitudinal channels with a uniform distribution,and microscopic pores were present in the channel wall.The spatial micro topological structure and extracellular matrix were conducive to the adhesion,survival and migration of neural stem cells.The scaffold promoted the directional growth of dorsal root ganglion neurites,and showed strong potential for myelin regeneration.Furthermore,we transplanted the porcine decellularized optic nerve containing neurotrophin-3-overexpressing Schwann cells in a rat model of T10 spinal cord defect in vivo.Four weeks later,the regenerating axons grew straight,the myelin sheath in the injured/transplanted area recovered its structure,and simultaneously,the number of inflammatory cells and the expression of chondroitin sulfate proteoglycans were reduced.Together,these findings suggest that porcine decellularized optic nerve loaded with Schwann cells overexpressing neurotrophin-3 promotes the directional growth of regenerating spinal cord axons as well as myelin regeneration.All procedures involving animals were conducted in accordance with the ethical standards of the Institutional Animal Care and Use Committee of Sun Yat-sen University(approval No.SYSU-IACUC-2019-B034)on February 28,2019.
文摘Neuropathologies include the deterioration and damage of the nervous system,especially neurons present in the brain,spinal cord and peripheral nervous system.Damage or alternations in neurons makes their structure and functionality abnormal.Every year over 90,000 people get affected by neurodegenerative diseases in the USA.Among all the neurological pathologies,
基金supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT)(Nos. 2021R1I1A1A01043176 and2021R1A2C1091301)the framework of international cooperation program managed by the National Research Foundation of Korea (No.2021K2A9A2A06037540)+3 种基金Korean Fund for Regenerative Medicine funded by Ministry of Science and ICTMinistry of Health and Welfare (No. 2021M3E5E5096420, Republic of Korea)Korea Medical Device Development Fund grant funded by the Korea government(the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health&Welfare, Republic of Korea, the Ministry of Food and Drug Safety)(Project Number:202011B29)the GRRC program of the Gyeo nggi Province (Grant Number GRRC-KPU2021-A01, Multi-material Machining Innovative Technology Research Center)
文摘Porous titanium(Ti)scaffolds have been extensively utilized as bone substitute scaffolds due to their superior biocompatibility and excellent mechanical properties.However,naturally formed TiO2 on the surface limits fast osseointegration.Different biomolecules have been widely utilized to overcome this issue;however,homogeneous porous Ti scaffolds could not simultaneously deliver multiple biomolecules that have different release behaviors.In this study,functionally graded porous Ti scaffolds(FGPTs)with dense inner and porous outer parts were fabricated using a two-body combination and densification procedure.FGPTs with growth factor(BMP-2)and antibiotics(TCH)exhibited suitable mechanical properties as bone substituting material and presented good structural stability.The release of BMP-2 was considerably prolonged,whereas the release of TCH was comparable to that of homogenous porous titanium scaffolds(control group).The osteogenic differentiation obtained using FGPTs was maintained due to the prolonged release of BMP-2.The antimicrobial properties of these scaffolds were verified using S.aureus in terms of prior release time.In addition,various candidates for graded porous Ti scaffolds with altered pore characteristics were presented.
文摘Nerve diseases including acute injury such as peripheral nerve injury(PNI),spinal cord injury(SCI)and traumatic brain injury(TBI),and chronic disease like neurodegeneration disease can cause various function disorders of nervous system,such as those relating to memory and voluntary movement.These nerve diseases produce great burden for individual families and the society,for which a lot of efforts have been made.Axonal pathways represent a unidirectional and aligned architecture allowing systematic axonal development within the tissue.Following a traumatic injury,the intricate architecture suffers disruption leading to inhibition of growth and loss of guidance.Due to limited capacity of the body to regenerate axonal pathways,it is desirable to have biomimetic approach that has the capacity to graft a bridge across the lesion while providing optimal mechanical and biochemical cues for tissue regeneration.And for central nervous system injury,one more extra precondition is compulsory:creating a less inhibitory surrounding for axonal growth.Electrospinning is a cost-effective and straightforward technique to fabricate extracellular matrix(ECM)-like nanofibrous structures,with various fibrous forms such as random fibers,aligned fibers,3D fibrous scaffold and core-shell fibers from a variety of polymers.The diversity and versatility of electrospinning technique,together with functionalizing cues such as neurotrophins,ECM-based proteins and conductive polymers,have gained considerable success for the nerve tissue applications.We are convinced that in the future the stem cell therapy with the support of functionalized electrospun nerve scaffolds could be a promising therapy to cure nerve diseases.
基金supported by grants from the National Natural Science Foundation of China(82172430 and 82272505)University Grants Committee,Research Grants Council of the Hong Kong Special Administrative Region,China(14108720,14121721,14202920,N_CUHK472/22,C7030-18G,T13-402/17-N and AoE/M-402/20)+1 种基金Heath Medical Research Fund(HMRF)Hong Kong(16170951,17180831,08190416 and 09203436)Hong Kong Innovation Technology Commission Funds(PRP/050/19FX).
文摘Lacking self-repair abilities,injuries to articular cartilage can lead to cartilage degeneration and ultimately result in osteoarthritis.Tissue engineering based on functional bioactive scaffolds are emerging as promising approaches for articular cartilage regeneration and repair.Although the use of cell-laden scaffolds prior to implantation can regenerate and repair cartilage lesions to some extent,these approaches are still restricted by limited cell sources,excessive costs,risks of disease transmission and complex manufacturing practices.Acellular approaches through the recruitment of endogenous cells offer great promise for in situ articular cartilage regeneration.In this study,we propose an endogenous stem cell recruitment strategy for cartilage repair.Based on an injectable,adhesive and self-healable o-alg-THAM/gel hydrogel system as scaffolds and a biophysio-enhanced bioactive microspheres engineered based on hBMSCs secretion during chondrogenic differentiation as bioactive supplement,the as proposed functional material effectively and specifically recruit endogenous stem cells for cartilage repair,providing new insights into in situ articular cartilage regeneration.