Physiological repair of large-sized bone defects is great challenging in clinic due to a lack of ideal grafts suitable for bone regeneration.Decalcified bone matrix(DBM)is considered as an ideal bone regeneration scaf...Physiological repair of large-sized bone defects is great challenging in clinic due to a lack of ideal grafts suitable for bone regeneration.Decalcified bone matrix(DBM)is considered as an ideal bone regeneration scaffold,but low cell seeding efficiency and a poor osteoinductive microenvironment greatly restrict its application in large-sized bone regeneration.To address these problems,we proposed a novel strategy of bone regeneration units(BRUs)based on microgels produced by photo-crosslinkable and microfluidic techniques,containing both the osteogenic ingredient DBM and vascular endothelial growth factor(VEGF)for accurate biomimic of an osteoinductive microenvironment.The physicochemical properties of microgels could be precisely controlled and the microgels effectively promoted adhesion,proliferation,and osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)in vitro.BRUs were successfully constructed by seeding BMSCs onto microgels,which achieved reliable bone regeneration in vivo.Finally,by integrating the advantages of BRUs in bone regeneration and the advantages of DBM scaffolds in 3D morphology and mechanical strength,a BRU-loaded DBM framework successfully regenerated bone tissue with the desired 3D morphology and effectively repaired a large-sized bone defect of rabbit tibia.The current study developed an ideal bone biomimetic microcarrier and provided a novel strategy for bone regeneration and large-sized bone defect repair.展开更多
Cartilage tissue engineering is a promising strategy for repairing cartilage defects.However,achieving satisfactory cartilage regeneration in vitro and maintaining its stability in vivo remains a challenge.The key to ...Cartilage tissue engineering is a promising strategy for repairing cartilage defects.However,achieving satisfactory cartilage regeneration in vitro and maintaining its stability in vivo remains a challenge.The key to achieving this goal is establishing an efficient cartilage regeneration culture system to retain sufficient active cells with physiological functions,generate abundant cartilage extracellular matrix(ECM)and maintain a low level of cartilage ECM degradation.The current chondrogenic medium(CM)can effectively promote cartilage ECM production;however,it has a negative effect on cell proliferation.Meanwhile,the specific c-Jun N-terminal kinase pathway inhibitor SP600125 promotes chondrocyte proliferation but inhibits ECM synthesis.Here,we aimed to construct a three-dimensional cartilage regeneration model using a polyglycolic acid/polylactic acid scaffold in combination with chondrocytes to investigate the effect of different culture modes with CM and SP600125 on in vitro cartilage regeneration and their long-term outcomes in vivo systematically.Our results demonstrate that the long-term combination of CM and SP600125 made up for each other and maximized their respective advantages to obtain optimal cartilage regeneration in vitro.Moreover,the long-term combination achieved stable cartilage regeneration after implantation in vivo with a relatively low initial cell-seeding concentration.Therefore,the long-term combination of CM and SP600125 enhanced in vitro and in vivo cartilage regeneration stability with fewer initial seeding cells and thus optimized the cartilage regeneration culture system.展开更多
Tissue-engineered cartilage regeneration by bone marrow stromal cells(BMSCs)is considered an ideal method.However,how to regulate BMSCs to regenerate specific types of cartilage remains unclear,which significantly lim...Tissue-engineered cartilage regeneration by bone marrow stromal cells(BMSCs)is considered an ideal method.However,how to regulate BMSCs to regenerate specific types of cartilage remains unclear,which significantly limits its clinical translation and leads to suboptimal clinical effects.Herein,we systematically explored the role of native ear and articular cartilage niches on the differentiation fate of BMSCs and the type of regenerated cartilage.First,we prepared two types of acellular cartilage sheets(ACSs)and two types of chondrocytes.Then green fluorescent protein-labeled BMSCs were seeded on two types of ACSs with or without corresponding types of chondrocytes using a sandwich model and directed or cross-implanted them into native cartilage niches.After one year of in vivo culture,cell tracking and the results of histological results showed that the native cartilage niches were capable of regulating BMSCs regeneration into specific types of cartilage that were consistent with the cartilage types of the implanted sites.Furthermore,even when the type of niche formed by ACSs or the biomimetic cartilage niche constructed by specific types of ACSs and specific types of chondrocytes did not match with the native cartilage niche,the native cartilage niche continued to determine the type of cartilage regenerated by implanted BMSCs and chondrocytes.All our results provide sufficient evidence for specific types of cartilage regeneration using chondrogenic potential cells,such as mesenchymal stem cells and chondrocytes.展开更多
基金financially supported by the National Key Research and Development Program of China(2017YFC1103900)the National Natural Science Foundation of China(81871502,81701843,and 81671837)+3 种基金the Shanghai Excellent Technical Leader(18XD1421500)the Program of Shanghai Academic/Technology Research Leader(19XD1431100)the Shanghai Collaborative Innovation Program on Regenerative Medicine and Stem Cell Research(2019CXJQ01)the Clinical Research Plan of SHDC(No.SHDC2020CR2045B).
文摘Physiological repair of large-sized bone defects is great challenging in clinic due to a lack of ideal grafts suitable for bone regeneration.Decalcified bone matrix(DBM)is considered as an ideal bone regeneration scaffold,but low cell seeding efficiency and a poor osteoinductive microenvironment greatly restrict its application in large-sized bone regeneration.To address these problems,we proposed a novel strategy of bone regeneration units(BRUs)based on microgels produced by photo-crosslinkable and microfluidic techniques,containing both the osteogenic ingredient DBM and vascular endothelial growth factor(VEGF)for accurate biomimic of an osteoinductive microenvironment.The physicochemical properties of microgels could be precisely controlled and the microgels effectively promoted adhesion,proliferation,and osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)in vitro.BRUs were successfully constructed by seeding BMSCs onto microgels,which achieved reliable bone regeneration in vivo.Finally,by integrating the advantages of BRUs in bone regeneration and the advantages of DBM scaffolds in 3D morphology and mechanical strength,a BRU-loaded DBM framework successfully regenerated bone tissue with the desired 3D morphology and effectively repaired a large-sized bone defect of rabbit tibia.The current study developed an ideal bone biomimetic microcarrier and provided a novel strategy for bone regeneration and large-sized bone defect repair.
基金supported by the National Key Research and Development Program of China(2017YFC1103900 and 2018YFC1105800)the National Natural Science Foundation of China(81871502 and 81701843)+3 种基金the Program of Shanghai Academic/Technology Research Leader(19XD1431100)the Shanghai Collaborative Innovation Program on Regenerative Medicine and Stem Cell Research(2019CXJQ01)the Clinical Research Plan of SHDC(No.SHDC2020CR2045B),Shanghai Municipal Key Clinical Specialty(shslczdzk06601)Biomaterials and Regenerative Medicine Institute Cooperative Research Project,Shanghai Jiao Tong University School of Medicine(2022LHA07).
文摘Cartilage tissue engineering is a promising strategy for repairing cartilage defects.However,achieving satisfactory cartilage regeneration in vitro and maintaining its stability in vivo remains a challenge.The key to achieving this goal is establishing an efficient cartilage regeneration culture system to retain sufficient active cells with physiological functions,generate abundant cartilage extracellular matrix(ECM)and maintain a low level of cartilage ECM degradation.The current chondrogenic medium(CM)can effectively promote cartilage ECM production;however,it has a negative effect on cell proliferation.Meanwhile,the specific c-Jun N-terminal kinase pathway inhibitor SP600125 promotes chondrocyte proliferation but inhibits ECM synthesis.Here,we aimed to construct a three-dimensional cartilage regeneration model using a polyglycolic acid/polylactic acid scaffold in combination with chondrocytes to investigate the effect of different culture modes with CM and SP600125 on in vitro cartilage regeneration and their long-term outcomes in vivo systematically.Our results demonstrate that the long-term combination of CM and SP600125 made up for each other and maximized their respective advantages to obtain optimal cartilage regeneration in vitro.Moreover,the long-term combination achieved stable cartilage regeneration after implantation in vivo with a relatively low initial cell-seeding concentration.Therefore,the long-term combination of CM and SP600125 enhanced in vitro and in vivo cartilage regeneration stability with fewer initial seeding cells and thus optimized the cartilage regeneration culture system.
基金This research was supported by the National Key Research and Development Program of China(2017YFC1103900)the National Natural Science Foundation of China(81671837,81871502)+1 种基金the Shanghai Collaborative Innovation Program on Regenerative Medicine and Stem Cell Research(2019CXJQ01)Clinical Research Plan of SHDC(SHDC2020CR2045B).
文摘Tissue-engineered cartilage regeneration by bone marrow stromal cells(BMSCs)is considered an ideal method.However,how to regulate BMSCs to regenerate specific types of cartilage remains unclear,which significantly limits its clinical translation and leads to suboptimal clinical effects.Herein,we systematically explored the role of native ear and articular cartilage niches on the differentiation fate of BMSCs and the type of regenerated cartilage.First,we prepared two types of acellular cartilage sheets(ACSs)and two types of chondrocytes.Then green fluorescent protein-labeled BMSCs were seeded on two types of ACSs with or without corresponding types of chondrocytes using a sandwich model and directed or cross-implanted them into native cartilage niches.After one year of in vivo culture,cell tracking and the results of histological results showed that the native cartilage niches were capable of regulating BMSCs regeneration into specific types of cartilage that were consistent with the cartilage types of the implanted sites.Furthermore,even when the type of niche formed by ACSs or the biomimetic cartilage niche constructed by specific types of ACSs and specific types of chondrocytes did not match with the native cartilage niche,the native cartilage niche continued to determine the type of cartilage regenerated by implanted BMSCs and chondrocytes.All our results provide sufficient evidence for specific types of cartilage regeneration using chondrogenic potential cells,such as mesenchymal stem cells and chondrocytes.
