Yu Qingwen, Meng Zhiyuan, Liu Yichao, Li Zehao, Sun Xing, Zhao Zheng
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070, China.
Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430070, China.
Polymers (Basel). 2021 Jul 14;13(14):2302. doi: 10.3390/polym13142302.
After an osteosarcoma excision, recurrence and bone defects are significant challenges for clinicians. In this study, the curcumin (Cur) loaded chitosan (CS) nanoparticles (CCNP) encapsulated silk fibroin (SF)/hyaluronic acid esterified by methacrylate (HAMA) (CCNPs-SF/HAMA) hydrogel for the osteosarcoma therapy and bone regeneration was developed by photocuring and ethanol treatment. The micro or nanofibers networks were observed in the CCNPs-SF/HAMA hydrogel. The FTIR results demonstrated that alcohol vapor treatment caused an increase in β-sheets of SF, resulting in the high compression stress and Young's modulus of CCNPs-SF/HAMA hydrogel. According to the water uptake analysis, SF caused a slight decrease in water uptake of CCNPs-SF/HAMA hydrogel while CCNPs could enhance the water uptake of it. The swelling kinetic results showed that both the CCNPs and the SF increased the swelling ratio of CCNPs-SF/HAMA hydrogel. The accumulative release profile of CCNPs-SF/HAMA hydrogel showed that the release of Cur from CCNPs-SF/HAMA hydrogel was accelerated when pH value was decreased from 7.4 to 5.5. Besides, compared with CCNPs, the CCNPs-SF/HAMA hydrogel had a more sustainable drug release, which was beneficial for the long-term treatment of osteosarcoma. In vitro assay results indicated that CCNPs-SF/HAMA hydrogel with equivalent Cur concentration of 150 μg/mL possessed both the effect of anti-cancer and promoting the proliferation of osteoblasts. These results suggest that CCNPs-SF/HAMA hydrogel with superior physical properties and the bifunctional osteosarcoma therapy and bone repair may be an excellent candidate for local cancer therapy and bone regeneration.
骨肉瘤切除术后,复发和骨缺损是临床医生面临的重大挑战。在本研究中,通过光固化和乙醇处理,开发了负载姜黄素(Cur)的壳聚糖(CS)纳米颗粒(CCNP)包裹的丝素蛋白(SF)/甲基丙烯酸酯化透明质酸(HAMA)(CCNPs-SF/HAMA)水凝胶用于骨肉瘤治疗和骨再生。在CCNPs-SF/HAMA水凝胶中观察到微纤维或纳米纤维网络。傅里叶变换红外光谱(FTIR)结果表明,乙醇蒸汽处理导致SF的β-折叠增加,从而使CCNPs-SF/HAMA水凝胶具有较高的压缩应力和杨氏模量。根据吸水率分析,SF使CCNPs-SF/HAMA水凝胶的吸水率略有下降,而CCNP可提高其吸水率。溶胀动力学结果表明,CCNP和SF均提高了CCNPs-SF/HAMA水凝胶的溶胀率。CCNPs-SF/HAMA水凝胶的累积释放曲线表明,当pH值从7.4降至5.5时,Cur从CCNPs-SF/HAMA水凝胶中的释放加速。此外,与CCNP相比,CCNPs-SF/HAMA水凝胶具有更持续的药物释放,这有利于骨肉瘤的长期治疗。体外试验结果表明,Cur浓度为150μg/mL的CCNPs-SF/HAMA水凝胶具有抗癌和促进成骨细胞增殖的作用。这些结果表明,具有优异物理性能以及双功能骨肉瘤治疗和骨修复作用的CCNPs-SF/HAMA水凝胶可能是局部癌症治疗和骨再生的理想候选材料。