Ferretti Mario, Marra Kacey G, Kobayashi Kenji, Defail Alicia J, Chu Constance R
Cartilage Restoration Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Tissue Eng. 2006 Sep;12(9):2657-63. doi: 10.1089/ten.2006.12.2657.
Polyethylene glycol (PEG) hydrogels show promise as scaffolds for growth factor delivery to enhance cartilage repair. However, methods to control growth factor release in vivo are needed. We have recently shown that in vitro polymer degradation and in vitro growth factor release kinetics can be altered using PEG crosslinked with different concentrations of genipin. However, the degradation and behavior of PEG-genipin in vivo within the cartilage repair site are unknown. This study was conducted to test the hypotheses that the degradation of PEG-genipin can be altered in vivo within osteochondral defects by changing the concentration of genipin, and that PEG-genipin is biocompatible within the mammalian diarthrodial environment. PEG-genipin cylindrical polymers crosslinked using 8mM, 17.6 mM, or 35.2 mM of genipin were implanted into osteochondral defects made in the trochlea of 24 male Sprague- Dawley rats (48 knees). Rats were sacrificed at 5 weeks and gross, cross-sectional, and histologic assessments were performed. Altering the genipin concentration changed the in vivo degradation properties of the hydrogel ( p < 0.01). Consistent with in vitro findings, polymer degradation was inversely related to the concentration of genipin. Near-complete degradation was seen at 8 mM, intermediate degradation at 17.6 mM, and minimal degradation at 35.2 mM. The results of this study show the degradation of PEGgenipin can be altered in vivo within osteochondral defects by changing the concentration of genipin and that PEG-genipin is biocompatible within osteochondral defects. This new in vivo data support potential use of PEG-genipin polymer as an innovative delivery system to control in vivo release of growth factors for improving articular cartilage repair.
聚乙二醇（PEG）水凝胶有望作为生长因子递送支架，以促进软骨修复。然而，需要控制体内生长因子释放的方法。我们最近发现，使用与不同浓度京尼平交联的PEG可以改变体外聚合物降解和体外生长因子释放动力学。然而，PEG-京尼平在软骨修复部位体内的降解和行为尚不清楚。本研究旨在检验以下假设：通过改变京尼平浓度，PEG-京尼平在体内骨软骨缺损处的降解可以改变，并且PEG-京尼平在哺乳动物滑膜环境中具有生物相容性。将使用8 mM、17.6 mM或35.2 mM京尼平交联的PEG-京尼平圆柱形聚合物植入24只雄性Sprague-Dawley大鼠（48个膝关节）滑车处的骨软骨缺损中。在5周时处死大鼠，并进行大体、横截面和组织学评估。改变京尼平浓度改变了水凝胶的体内降解特性（p<0.01）。与体外研究结果一致，聚合物降解与京尼平浓度呈负相关。在8 mM时观察到近乎完全降解，在17.6 mM时为中度降解，在35.2 mM时为最小降解。本研究结果表明，通过改变京尼平浓度，PEG-京尼平在体内骨软骨缺损处的降解可以改变，并且PEG-京尼平在骨软骨缺损处具有生物相容性。这些新的体内数据支持将PEG-京尼平聚合物作为一种创新的递送系统，用于控制体内生长因子释放以改善关节软骨修复的潜在用途。
