Cao Runfeng, Zhan Anqi, Ci Zheng, Wang Cheng, She Yunlang, Xu Yong, Xiao Kaiyan, Xia Huitang, Shen Li, Meng Depeng, Chen Chang
Department of Cardiothoracic Surgery, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, Shanghai, China.
Front Cell Dev Biol. 2021 Feb 19;9:639006. doi: 10.3389/fcell.2021.639006. eCollection 2021.
It is challenging to develop a biphasic scaffold with biomimetic compositional, structural, and functional properties to achieve concomitant repair of both superficial cartilage and subchondral bone in osteochondral defects (OCDs). This study developed a biomimsubchondraletic biphasic scaffold for OCD repair via an iterative layered lyophilization technique that controlled the composition, substrate stiffness, and pore size in each phase of the scaffold. The biphasic scaffold consisted of a superficial decellularized cartilage matrix (DCM) and underlying decalcified bone matrix (DBM) with distinct but seamlessly integrated phases that mimicked the composition and structure of osteochondral tissue, in which the DCM phase had relative low stiffness and small pores (approximately 134 μm) and the DBM phase had relative higher stiffness and larger pores (approximately 336 μm). results indicated that the biphasic scaffold was biocompatible for bone morrow stem cells (BMSCs) adhesion and proliferation, and the superficial DCM phase promoted chondrogenic differentiation of BMSCs, as indicated by the up-regulation of cartilage-specific gene expression (ACAN, Collagen II, and SOX9) and sGAG secretion; whereas the DBM phase was inducive for osteogenic differentiation of BMSCs, as indicated by the up-regulation of bone-specific gene expression (Collagen I, OCN, and RUNX2) and ALP deposition. Furthermore, compared with the untreated control group, the biphasic scaffold significantly enhanced concomitant repair of superficial cartilage and underlying subchondral bone in a rabbit OCD model, as evidenced by the ICRS macroscopic and O'Driscoll histological assessments. Our results demonstrate that the biomimetic biphasic scaffold has a good osteochondral repair effect.
开发一种具有仿生成分、结构和功能特性的双相支架,以实现骨软骨缺损(OCD)中表层软骨和软骨下骨的同步修复具有挑战性。本研究通过迭代分层冻干技术开发了一种用于OCD修复的仿生双相支架,该技术可控制支架各相的组成、基质硬度和孔径。双相支架由表层脱细胞软骨基质(DCM)和下层脱钙骨基质(DBM)组成,两相截然不同但无缝整合,模仿了骨软骨组织的组成和结构,其中DCM相具有相对较低的硬度和较小的孔隙(约134μm),DBM相具有相对较高的硬度和较大的孔隙(约336μm)。结果表明,双相支架对骨髓干细胞(BMSC)的粘附和增殖具有生物相容性,表层DCM相促进了BMSC的软骨分化,软骨特异性基因表达(ACAN、胶原蛋白II和SOX9)上调和sGAG分泌表明了这一点;而DBM相有利于BMSC的成骨分化,骨特异性基因表达(胶原蛋白I、OCN和RUNX2)上调和ALP沉积表明了这一点。此外,与未治疗的对照组相比,双相支架在兔OCD模型中显著增强了表层软骨和下层软骨下骨的同步修复,ICRS宏观评估和O'Driscoll组织学评估证明了这一点。我们的结果表明,仿生双相支架具有良好的骨软骨修复效果。