Abstract：
Femoral head necrosis is a debilitating disorder that typically caused by impaired blood supply to the hip joint. In this study, a novel injectable hydrogel based on Oxidized Carboxymethyl Cellulose (OCMC)-Carboxymethyl Chitosan (CMCS) polymers containing an angiogenesis stimulator peptide (QK) with a non-toxic crosslinking interaction (Schiff based reaction) was synthesized to enhance angiogenesis following femoral head necrosis in an animal model. The physicochemical features of fabricated injectable hydrogel were analyzed by FTIR, swelling and degradation rate, rheometry, and peptide release. Also, the safety and efficacy were evaluated following an in vitro hydrogel injection study and an avascular necrosis (AVN) animal model. According to the results, the hydrogel exhibited an appropriate swelling ratio and water uptake (>90 %, 24 h) as well as a suitable degradation rate over 21 days accompanied by a continuous peptide release. Also, data showed that hydrogels containing QK peptide boosted the proliferation, differentiation, angiogenesis, and osteogenic potential of both Bone Marrow mesenchymal Stem Cells (BM-MSCs) and human umbilical vein endothelial cells (HUVECs) (****p < 0.0001 and ***p < 0.001, respectively). Furthermore, molecular and histological evaluations significantly demonstrated the overexpression of Runx2, Osteocalcin, Collagen I, VEGF and CD34 genes (**p < 0.01 and ***p < 0.001, respectively), and also femoral head necrosis was effectively prohibited, and more blood vessels were detected in defect area by OCMC-CMCS hydrogel containing QK peptide (bone trabeculae >9000, ***p < 0.001). In conclusion, the findings demonstrate that OCMC-CMCS-QK injectable hydrogel could be considered as an impressive therapeutic construct for femoral head AVN healing.
摘要：
股骨头坏死是一种使人衰弱的疾病，通常由髋关节的血液供应受损引起。在这项研究中,在动物模型中,合成了一种新型的可注射水凝胶,其基于氧化羧甲基纤维素(OCMC)-羧甲基壳聚糖(CMCS)聚合物,其含有具有无毒交联相互作用(席夫基反应)的血管生成刺激肽(QK),以增强股骨头坏死后的血管生成。通过FTIR分析了制备的可注射水凝胶的物理化学特征，溶胀和降解率，流变仪,和肽释放。此外，在体外水凝胶注射研究和无血管坏死(AVN)动物模型后评估安全性和有效性.根据结果,水凝胶表现出适当的溶胀率和吸水率(>90%，24h）以及经过21天的合适降解速率，并伴有连续的肽释放。此外，数据显示，含有QK肽的水凝胶促进了增殖，分化,血管生成,骨髓间充质干细胞（BM-MSC）和人脐静脉内皮细胞（HUVEC）的成骨潜能（分别为****p<0.0001和***p<0.001）。此外，分子和组织学评估显着证明了Runx2，骨钙蛋白的过度表达，胶原蛋白I,VEGF和CD34基因（分别为**p<0.01和***p<0.001），股骨头坏死也被有效禁止，含有QK肽的OCMC-CMCS水凝胶在缺损区域检测到更多的血管（骨小梁>9000，***p<0.001）。总之,研究结果表明，OCMC-CMCS-QK可注射水凝胶可被认为是股骨头AVN愈合的令人印象深刻的治疗结构。
