医学博士，博士后，现为上海交通大学附属第六人民医院骨科主治医师。毕业于北京协和医院，师从中国骨科学泰斗邱贵兴院士。擅长脊柱侧弯，腰腿痛，骨质疏松，关节炎等骨科疾病。哈佛大学医学院访问学者，专攻3D打印方向，主持国家自然科学基金、上海市浦江人才计划等5项科研项目。第一作者、通讯作者发表英文SCI论文16篇，担任十余本杂志SCI杂志的中青年编委和审稿人。

Topic title: 3D Printed Biomimetic Scaffold for Integrative Osteochondral Regeneration

Abstract:

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. With the layer-by-layer fabrication strategies, 3D printing becomes a promising technology to replicate the stratified zonal architecture and vary micro-structures 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, which leads to undistinguished spatial variations and subsequently inefficient regenerations. Here, we introduce 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 (nHA), and tasquinimod (TA) can physically and biologically separate the cartilage layer (TA-mixed, chondrocytes-load gelatin methacrylate) from the subchondral bond layer (porous PCL). The introduction of the calcified interfacial layer preserves the as-designed independent biological environment in each layer for both cartilage and bone regeneration, successfully inhibits vascular invasion into the cartilage layer and prevents hyaluronic cartilage calcification. The improved integrative regeneration of cartilage and subchondral bone have been validated via gross examination, micro-computed tomography (micro-CT), and histological and immunohistochemical analysis based on in vivo rat model. Moreover, the gene and protein expression studies identify a key role of CAV-1 to promote angiogenesis by the Wnt/β-catenin pathway, and indicate that TA in the calcified layer block angiogenesis through inhibiting CAV-1.