Xu Jietao, Fahmy-Garcia Shorouk, Wesdorp Marinus A, Kops Nicole, Forte Lucia, De Luca Claudio, Misciagna Massimiliano Maraglino, Dolcini Laura, Filardo Giuseppe, Labberté Margot, Vancíková Karin, Kok Joeri, van Rietbergen Bert, Nickel Joachim, Farrell Eric, Brama Pieter A J, van Osch Gerjo J V M
Department of Orthopedics and Sports Medicine, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands.
Department of Oral and Maxillofacial Surgery, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands.
J Funct Biomater. 2023 Feb 16;14(2):111. doi: 10.3390/jfb14020111.
Despite promising clinical results in osteochondral defect repair, a recently developed bi-layered collagen/collagen-magnesium-hydroxyapatite scaffold has demonstrated less optimal subchondral bone repair. This study aimed to improve the bone repair potential of this scaffold by adsorbing bone morphogenetic protein 2 (BMP-2) and/or platelet-derived growth factor-BB (PDGF-BB) onto said scaffold. The in vitro release kinetics of BMP-2/PDGF-BB demonstrated that PDGF-BB was burst released from the collagen-only layer, whereas BMP-2 was largely retained in both layers. Cell ingrowth was enhanced by BMP-2/PDFG-BB in a bovine osteochondral defect ex vivo model. In an in vivo semi-orthotopic athymic mouse model, adding BMP-2 or PDGF-BB increased tissue repair after four weeks. After eight weeks, most defects were filled with bone tissue. To further investigate the promising effect of BMP-2, a caprine bilateral stifle osteochondral defect model was used where defects were created in weight-bearing femoral condyle and non-weight-bearing trochlear groove locations. After six months, the adsorption of BMP-2 resulted in significantly less bone repair compared with scaffold-only in the femoral condyle defects and a trend to more bone repair in the trochlear groove. Overall, the adsorption of BMP-2 onto a Col/Col-Mg-HAp scaffold reduced bone formation in weight-bearing osteochondral defects, but not in non-weight-bearing osteochondral defects.
尽管在骨软骨缺损修复方面取得了令人鼓舞的临床结果,但最近开发的双层胶原蛋白/胶原蛋白-镁羟基磷灰石支架在软骨下骨修复方面表现欠佳。本研究旨在通过将骨形态发生蛋白2(BMP-2)和/或血小板衍生生长因子-BB(PDGF-BB)吸附到所述支架上来提高该支架的骨修复潜力。BMP-2/PDGF-BB的体外释放动力学表明,PDGF-BB从仅含胶原蛋白的层中快速释放,而BMP-2在两层中基本都能保留。在牛骨软骨缺损体外模型中,BMP-2/PDFG-BB促进了细胞向内生长。在体内半原位无胸腺小鼠模型中,添加BMP-2或PDGF-BB可在四周后增加组织修复。八周后,大多数缺损被骨组织填充。为进一步研究BMP-2的显著效果,使用了山羊双侧膝关节骨软骨缺损模型,在负重的股骨髁和非负重的滑车沟部位制造缺损。六个月后,与仅使用支架相比,在股骨髁缺损处吸附BMP-2导致骨修复明显减少,而在滑车沟处有骨修复增加的趋势。总体而言,将BMP-2吸附到Col/Col-Mg-HAp支架上会减少负重骨软骨缺损处的骨形成,但在非负重骨软骨缺损处则不然。