Lin Dan, Cai Bolei, Wang Le, Cai Lisha, Wang Zihao, Xie Jirong, Lv Qian-Xin, Yuan Yuan, Liu Changsheng, Shen Steve Gf
Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, PR China; Engineering Research Center for Biomaterials of Ministry of Education, Key Laboratory for Ultrafine Materials of Ministry of Education, The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, PR China.
Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, PR China; State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, PR China.
Biomaterials. 2020 Sep;253:120095. doi: 10.1016/j.biomaterials.2020.120095. Epub 2020 May 6.
Defects of either articular cartilage or subchondral bone would destroy the structural integrity and functionality of the joint. Reconstruction of osteochondral defects requires difunctional scaffolds that simultaneously induce cartilage and subchondral bone morphogenesis, however, high-performance cartilage reconstructive scaffolds remain a considerable challenge. In this study, a solvent-free urethane crosslinking and spontaneous pore-forming procedure under room temperature was proposed and optimized to produce PEGylated poly(glycerol sebacate) (PEGS) scaffolds with controllable crosslinking degrees and hierarchical macro-/micro-porosities. Based on the economical and feasible preparative approach, the viscoelastic PEGS-12h with low crosslinking degree was demonstrated to significantly stimulate chondrogenic differentiation, maintain chondrocyte phenotype and enhance cartilage matrix secretion compared to elastic polymer with high crosslinking degree, emphasizing the importance of matrix viscoelasticity in cartilage regeneration. On this basis, the viscoelastic low-crosslinked PEGS-12h was combined with the well-acknowledged osteoinductive mesoporous bioactive glass (MBG) to construct a difunctional PEGS/MBG bilayer scaffold, and evaluated in a full-thickness osteochondral defect model in vivo. The PEGS/MBG bilayer scaffold successfully reconstructed well-integrated articular hyaline cartilage and its subchondral bone in 12 weeks, exhibiting extraordinary regenerative efficiency. The results indicated that the viscoelastic PEGS scaffold and PEGS/MBG bilayer scaffold proposed in this study made an excellent candidate for cartilage and osteochondral regeneration, and was expected for clinical translation in the future.
关节软骨或软骨下骨的缺陷都会破坏关节的结构完整性和功能。骨软骨缺损的修复需要双功能支架，以同时诱导软骨和软骨下骨的形态发生，然而，高性能的软骨修复支架仍然是一个巨大的挑战。在本研究中，我们提出并优化了一种在室温下无溶剂聚氨酯交联和自发成孔的方法，以制备具有可控交联度和分级大/微孔结构的聚乙二醇化聚癸二酸甘油酯（PEGS）支架。基于这种经济可行的制备方法，与高交联度的弹性聚合物相比，低交联度的粘弹性PEGS-12h被证明能显著刺激软骨细胞分化、维持软骨细胞表型并增强软骨基质分泌，强调了基质粘弹性在软骨再生中的重要性。在此基础上，将粘弹性低交联的PEGS-12h与公认的骨诱导性介孔生物活性玻璃（MBG）相结合，构建了一种双功能PEGS/MBG双层支架，并在体内全层骨软骨缺损模型中进行了评估。PEGS/MBG双层支架在12周内成功重建了整合良好的关节透明软骨及其软骨下骨，展现出非凡的再生效率。结果表明，本研究中提出的粘弹性PEGS支架和PEGS/MBG双层支架是软骨和骨软骨再生的优秀候选材料，有望在未来实现临床转化。
