Osteoarthritis (OA) is one of the most common chronic diseases, causing degenerative changes in articular cartilage and subchondral bones. To date, there is no effective drug to delay the progression of OA in clinical practice. In this study, we synthesized and prepared a new thermosensitive hydrogel called PHA hydrogel, a mixture of normal poloxamer 407 and hyaluronic acid-modified poloxamer 407, and we investigated the effects of the PHA hydrogel loaded with keratinocyte growth factor 2 (KGF-2) on rats with papain-induced OA. First, we evaluated the safety of the PHA hydrogel in vitro and in vivo. The results showed that the PHA hydrogel had suitable osmotic pressure and no obvious cytotoxicity or adverse reactions after intra-articular injection. In addition, the PHA hydrogel improved the stability of KGF-2. Next, we studied the effects of the PHA hydrogel loaded with KGF-2 (PHA-KGF-2) on OA in rats. PHA-KGF-2 significantly improved the morphology and inflammation of the articular cartilage, reduced the loss of proteoglycan, and balanced collagen metabolism compared with KGF-2 alone. These data demonstrated that the PHA hydrogel is a safe biomaterial that can protect KGF-2, and thus is a promising therapeutic strategy for patients with OA.

骨关节炎（OA）是最常见的慢性疾病之一，会导致关节软骨和软骨下骨的退行性变化。迄今为止，临床实践中还没有有效的药物可以延缓 OA 的进展。在这项研究中，我们合成并制备了一种称为 PHA 水凝胶的新型热敏水凝胶，它是普通泊洛沙姆 407 和透明质酸修饰的泊洛沙姆 407 的混合物，我们研究了负载角质形成细胞生长因子 2 (KGF-2) 的 PHA 水凝胶的效果木瓜蛋白酶诱导的 OA 大鼠。首先，我们评估了 PHA 水凝胶的体外和体内安全性. 结果表明，PHA水凝胶具有适宜的渗透压，关节内注射后无明显细胞毒性或不良反应。此外，PHA 水凝胶提高了 KGF-2 的稳定性。接下来，我们研究了负载有 KGF-2 (PHA-KGF-2) 的 PHA 水凝胶对大鼠 OA 的影响。与单独使用KGF-2相比，PHA-KGF-2显着改善了关节软骨的形态和炎症，减少了蛋白多糖的损失，平衡了胶原代谢。这些数据表明，PHA 水凝胶是一种可以保护 KGF-2 的安全生物材料，因此对于 OA 患者来说是一种很有前景的治疗策略。