The bidirectional relationship between osteochondral defects(OCD)and osteoarthritis(OA),with each condition exacerbating the other,makes OCD regeneration in the presence of OA challenging.Type II collagen(Col2)is impo...The bidirectional relationship between osteochondral defects(OCD)and osteoarthritis(OA),with each condition exacerbating the other,makes OCD regeneration in the presence of OA challenging.Type II collagen(Col2)is important in OCD regeneration and the management of OA,but its potential applications in cartilage tissue engineering are significantly limited.This study investigated the regeneration capacity of Col2 scaffolds in critical-sized OCDs under surgically induced OA conditions and explored the underlying mechanisms that promoted OCD regeneration.Furthermore,the repair potential of Col2 scaffolds was validated in over critical-sized OCD models.After 90 days or 150 days since scaffold implantation,complete healing was observed histologically in critical-sized OCD,evidenced by the excellent integration with surrounding native tissues.The newly formed tissue biochemically resembled adjacent natural tissue and exhibited comparable biomechanical properties.The regenerated OA tissue demonstrated lower expression of genes associated with cartilage degradation than native OA tissue but comparable expression of genes related to osteochondral anabolism compared with normal tissue.Additionally,transcriptome and proteome analysis revealed the hindrance of TGF-β-Smad1/5/8 in regenerated OA tissue.In conclusion,the engrafting of Col2 scaffolds led to the successful regeneration of critical-sized OCDs under surgically induced OA conditions by inhibiting the TGF-β-Smad1/5/8 signaling pathway.展开更多
基金supported by General Research Fund,Research Grants Council,University Grants Committee,Hong Kong SAR(CityU 11205520 to Dong-An Wang)National Natural Science Foundation of China(NSFC51973180 to Dong-An Wang)+2 种基金Grant from Karolinska Institutet Ming Wai Lau Centre of Reparative Medicine (to Dong-An Wang)and, Grants from City University of Hong Kong (7020028, 7005949, 9231412, 9231486 to Dong-An Wang)Young scientists lifting project of Jiangsu Province, China (TJ-2022-072 to Hang Yao).
文摘The bidirectional relationship between osteochondral defects(OCD)and osteoarthritis(OA),with each condition exacerbating the other,makes OCD regeneration in the presence of OA challenging.Type II collagen(Col2)is important in OCD regeneration and the management of OA,but its potential applications in cartilage tissue engineering are significantly limited.This study investigated the regeneration capacity of Col2 scaffolds in critical-sized OCDs under surgically induced OA conditions and explored the underlying mechanisms that promoted OCD regeneration.Furthermore,the repair potential of Col2 scaffolds was validated in over critical-sized OCD models.After 90 days or 150 days since scaffold implantation,complete healing was observed histologically in critical-sized OCD,evidenced by the excellent integration with surrounding native tissues.The newly formed tissue biochemically resembled adjacent natural tissue and exhibited comparable biomechanical properties.The regenerated OA tissue demonstrated lower expression of genes associated with cartilage degradation than native OA tissue but comparable expression of genes related to osteochondral anabolism compared with normal tissue.Additionally,transcriptome and proteome analysis revealed the hindrance of TGF-β-Smad1/5/8 in regenerated OA tissue.In conclusion,the engrafting of Col2 scaffolds led to the successful regeneration of critical-sized OCDs under surgically induced OA conditions by inhibiting the TGF-β-Smad1/5/8 signaling pathway.
