Enhanced osteochondral regeneration with a 3D-Printed biomimetic scaffold featuring a calcified interfacial layer  

作　　者：Di Wu Kaiwen Zheng Wenjing Yin Bin Hu Mingzhao Yu Qingxiao Yu Xiaojuan Wei Jue Deng Changqing Zhang 

机构地区：[1]Department of Orthopedic Surgery,Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,No.600 Yishan Road,Shanghai,200233,China [2]Institute of Microsurgery on Extremities,Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,No.600 Yishan Road,Shanghai,200233,China [3]Shanghai Uniorlechnology Corporation,No.258 Xinzhuan Road,Shanghai,201612,China [4]Academy for Engineering&Technology,Fudan University,No.220 Handan Road,Shanghai,200433,China

出　　处：《Bioactive Materials》2024年第6期317-329,共13页生物活性材料（英文）

基　　金：supported by the National Natural Science Foundation of China(Grant No.82202690);the Shanghai Pujiang Program(2022PJD051);the China Postdoctoral Science Foundation(2022M712121);the Basic Science Program of Shanghai Sixth People’s Hospital(Grant No.ynqn202203).

摘　　要：The integrative regeneration of both articular cartilage and subchondral bone remains an unmet clinical need due to the difficulties of mimicking spatial complexity in native osteochondral tissues for artificial implants.Layer-by-layer fabrication strategies,such as 3D printing,have emerged as a promising technology replicating the stratified zonal architecture and varying microstructures and mechanical properties.However,the dynamic and circulating physiological environments,such as mass transportation or cell migration,usually distort the pre-confined biological properties in the layered implants,leading to undistinguished spatial variations and subsequently inefficient regenerations.This study introduced a biomimetic calcified interfacial layer into the scaffold as a compact barrier between a cartilage layer and a subchondral bone layer to facilitate osteogenic-chondrogenic repair.The calcified interfacial layer consisting of compact polycaprolactone(PCL),nano-hydroxyapatite,and tasquinimod(TA)can physically and biologically separate the cartilage layer(TA-mixed,chondrocytes-load gelatin methacrylate)from the subchondral bond layer(porous PCL).This introduction preserved the as-designed independent biological environment in each layer for both cartilage and bone regeneration,successfully inhibiting vascular invasion into the cartilage layer and preventing hyaluronic cartilage calcification owing to devascularization of TA.The improved integrative regeneration of cartilage and subchondral bone was validated through gross examination,micro-computed tomography(micro-CT),and histological and immunohistochemical analyses based on an in vivo rat model.Moreover,gene and protein expression studies identified a key role of Caveolin(CAV-1)in promoting angiogenesis through the Wnt/β-catenin pathway and indicated that TA in the calcified layer blocked angiogenesis by inhibiting CAV-1.

关 键 词：3D-printed scaffold Calcified interfacial layer CAV-1 Osteochondral regeneration Tasquinimod 

分 类 号：R318[医药卫生—生物医学工程] R68[医药卫生—基础医学]