Department of Clinical Sciences, Orthopaedic Research Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 300 West Drake Road, Fort Collins, CO, 80523.
Department of Biological Engineering, Center for Biomedical Engineering, Massachusetts Institute of Technology, 500 Technology Square, Cambridge, MA, 02139.
J Orthop Res. 2019 Nov;37(11):2307-2315. doi: 10.1002/jor.24414. Epub 2019 Aug 6.
The objective of this study was to improve cartilage repair and integration using self-assembling KLD hydrogel functionalized with platelet-derived growth factor-BB and heparin-binding insulin-like growth factor-1 with associated enzymatic trypsin pre-treatment of the native cartilage. Bilateral osteochondral defects were created at the central portion of the femoral trochlear groove of 48 skeletally mature, white New Zealand rabbits. One limb received a randomly assigned treatment and the contralateral limb served as the control. Treated defects were exposed to trypsin for 2 min and filled with self-assembling KLD hydrogel only, or associated to growth factors. All control limbs received KLD hydrogel alone or received only trypsin but not hydrogel. Ninety days post-defect creation, the rabbits were euthanized and magnetic resonance imaging, radiography, macroscopic evaluation, histology, and immunohistochemistry of the joint and repaired tissue were performed. Mixed model analyses of variance were utilized to assess the outcome parameters and individual comparisons were performed using Least Square Means procedure and differences with p-value < 0.05 were considered significant. Trypsin enzymatic pre-treatment improved cellular morphology, cluster formation and subchondral bone reconstitution. Platelet-derived growth factor-BB improved subchondral bone healing and basal integration. Heparin-binding insulin-like growth factor-1 associated with platelet-derived growth factor improved tissue and cell morphology. The authors conclude that self-assembling KLD hydrogel functionalized with platelet-derived growth factor and heparin-binding insulin-like growth factor-1 with associated enzymatic pre-treatment of the native cartilage with trypsin resulted in an improvement on the cartilage repair process. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2307-2315, 2019.
本研究的目的是通过自组装的 KLD 水凝胶与血小板衍生生长因子-BB 和肝素结合的胰岛素样生长因子-1 结合，并对天然软骨进行酶性胰蛋白酶预处理，从而改善软骨修复和整合。在 48 只骨骼成熟的白色新西兰兔的股骨滑车沟中央部分创建双侧骨软骨缺损。一条肢体接受随机分配的治疗，对侧肢体作为对照。处理后的缺损用胰蛋白酶暴露 2 分钟，仅用自组装的 KLD 水凝胶填充，或与生长因子联合使用。所有对照肢体仅接受 KLD 水凝胶或仅接受胰蛋白酶但不接受水凝胶。在创建缺损 90 天后，处死兔子，并对关节和修复组织进行磁共振成像、放射学、宏观评估、组织学和免疫组织化学检查。采用混合模型方差分析评估结果参数，并采用最小二乘均值程序进行个体比较，p 值<0.05 认为差异有统计学意义。胰蛋白酶酶预处理改善了细胞形态、簇形成和软骨下骨重建。血小板衍生生长因子-BB 改善了软骨下骨愈合和基底整合。与血小板衍生生长因子结合的肝素结合胰岛素样生长因子-1 改善了组织和细胞形态。作者得出结论，自组装的 KLD 水凝胶与血小板衍生生长因子和肝素结合的胰岛素样生长因子-1 结合，并对天然软骨进行酶性胰蛋白酶预处理，可改善软骨修复过程。© 2019 矫形研究协会。由 Wiley Periodicals, Inc. 出版。J 矫形研究 37:2307-2315, 2019。
