Osteochondral tissue is a highly specialized and complex tissue composed of articular cartilage and subchondral bone that are separated by a calcified cartilage interface.Multilayered or gradient scaffolds,often in co...Osteochondral tissue is a highly specialized and complex tissue composed of articular cartilage and subchondral bone that are separated by a calcified cartilage interface.Multilayered or gradient scaffolds,often in conjunction with stem cells and growth factors,have been developed to mimic the respective layers for osteochondral defect repair.In this study,we designed a hyaline cartilage-hypertrophic cartilage bilayer graft(RGD/RGDW)with chondrocytes.Previously,we demonstrated that RGD peptide-modified chondroitin sulfate cryogel(RGD group)is chondro-conductive and capable of hyaline cartilage formation.Here,we incorporated whitlockite(WH),a Mg2+-containing calcium phosphate,into RGD cryogel(RGDW group)to induce chondrocyte hypertrophy and form collagen X-rich hypertrophic cartilage.This is the first study to use WH to produce hypertrophic cartilage.Chondrocytes-laden RGDW cryogel exhibited significantly upregulated expression of hypertrophy markers in vitro and formed ectopic hypertrophic cartilage in vivo,which mineralized into calcified cartilage in bone microenvironment.Subsequently,RGD cryogel and RGDW cryogel were combined into bilayer(RGD/RGDW group)and implanted into rabbit osteochondral defect,where RGD layer supports hyaline cartilage regeneration and bioceramic-containing RGDW layer promotes calcified cartilage formation.While the RGD group(monolayer)formed hyaline-like neotissue that extends into the subchondral bone,the RGD/RGDW group(bilayer)regenerated hyaline cartilage tissue confined to its respective layer and promoted osseointegration for integrative defect repair.展开更多
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korean government(NRF-2021K1A3A1A57086407,NRF-2021R1A2C2008821,NRF-2022R1I1A1A01071991)Arun Kumar Rajendran was supported by the National Research Foundation of Korea(NRF)grant Brain Pool program funded by the Ministry of Science and ICT through the National Research Foundation of Korea(2020H1D3A1A04081286)The Institute of Engineering Research at Seoul National University provided research facilities,and additional support came from the SNU Engineering-Medicine Collaboration grant.
文摘Osteochondral tissue is a highly specialized and complex tissue composed of articular cartilage and subchondral bone that are separated by a calcified cartilage interface.Multilayered or gradient scaffolds,often in conjunction with stem cells and growth factors,have been developed to mimic the respective layers for osteochondral defect repair.In this study,we designed a hyaline cartilage-hypertrophic cartilage bilayer graft(RGD/RGDW)with chondrocytes.Previously,we demonstrated that RGD peptide-modified chondroitin sulfate cryogel(RGD group)is chondro-conductive and capable of hyaline cartilage formation.Here,we incorporated whitlockite(WH),a Mg2+-containing calcium phosphate,into RGD cryogel(RGDW group)to induce chondrocyte hypertrophy and form collagen X-rich hypertrophic cartilage.This is the first study to use WH to produce hypertrophic cartilage.Chondrocytes-laden RGDW cryogel exhibited significantly upregulated expression of hypertrophy markers in vitro and formed ectopic hypertrophic cartilage in vivo,which mineralized into calcified cartilage in bone microenvironment.Subsequently,RGD cryogel and RGDW cryogel were combined into bilayer(RGD/RGDW group)and implanted into rabbit osteochondral defect,where RGD layer supports hyaline cartilage regeneration and bioceramic-containing RGDW layer promotes calcified cartilage formation.While the RGD group(monolayer)formed hyaline-like neotissue that extends into the subchondral bone,the RGD/RGDW group(bilayer)regenerated hyaline cartilage tissue confined to its respective layer and promoted osseointegration for integrative defect repair.
