Department of Joint and Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, PR China; Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, PR China; Department of Emergency surgery, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, PR China; Shenzhen Key Laboratory of Cell Microenvironment, PR China.
Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, PR China.
Colloids Surf B Biointerfaces. 2022 Apr;212:112339. doi: 10.1016/j.colsurfb.2022.112339. Epub 2022 Jan 14.
The clinical treatment of open bone defects caused by accidental bone trauma, bone tumors, bone diseases and bone infections is challenging. In this study, we designed and fabricated a multifunctional alginate-based hydrogel that contains cannabidiol (CBD), SA@Cu/CBD hydrogel, for repairing open bone defects. The results of physicochemical characterization showed that the SA@Cu/CBD hydrogel was successfully prepared and showed a suitable swelling ratio, high thermal stability, and stable mechanical properties. In vitro evaluation of antibacterial activity indicated that more than 90% of S. aureus and E. coli were inhibited compared to the control group. The ALP activity assay showed that the ALP expression level of MC3T3-E1cells in SA@Cu/CBD hydrogel was approximately 2-fold higher than that in the control group on day 7 and 14. Additionally, compared to the control group, the level of mineralized deposits in SA@Cu/CBD hydrogel was also improved by about 2 times on day 14. The PCR results indicated the mRNA expression levels of osteogenic markers (ALP, Col1α1, OCN, and RUNX2 genes) and angiogenic markers (EGFL6 and VEGF genes) in SA@Cu/CBD hydrogel were significantly upregulated compared to that in the control group, and the mRNA expression levels of critical inflammatory cytokines (TNF-α and IL-1β) in the SA@Cu/CBD hydrogel were significantly down-regulated compared to that in SA@Cu hydrogel. Taken together, these results demonstrated that the SA@Cu/CBD hydrogel showed significantly anti-bacterial, anti-inflammation, angiogenic and osteogenic activities in vitro studies. Thus, SA@Cu/CBD hydrogels may be a promising candidate in repairing open bone defects.
意外骨创伤、骨肿瘤、骨病和骨感染导致的开放性骨缺损的临床治疗具有挑战性。在本研究中，我们设计并制备了一种含有大麻二酚（CBD）的多功能海藻酸钠水凝胶，即 SA@Cu/CBD 水凝胶，用于修复开放性骨缺损。理化特性表征结果表明，成功制备了 SA@Cu/CBD 水凝胶，其具有合适的溶胀比、高热稳定性和稳定的机械性能。体外抗菌活性评价表明，与对照组相比，金黄色葡萄球菌和大肠杆菌的抑制率超过 90%。ALP 活性测定表明，SA@Cu/CBD 水凝胶中 MC3T3-E1 细胞的 ALP 表达水平在第 7 天和第 14 天约为对照组的 2 倍。此外，与对照组相比，SA@Cu/CBD 水凝胶中的矿化沉积物水平在第 14 天也提高了约 2 倍。PCR 结果表明，与对照组相比，SA@Cu/CBD 水凝胶中成骨标志物（ALP、Col1α1、OCN 和 RUNX2 基因）和血管生成标志物（EGFL6 和 VEGF 基因）的 mRNA 表达水平显著上调，而 SA@Cu/CBD 水凝胶中关键炎症细胞因子（TNF-α和 IL-1β）的 mRNA 表达水平则显著下调。综上所述，这些结果表明，SA@Cu/CBD 水凝胶在体外研究中表现出显著的抗菌、抗炎、促血管生成和促骨生成活性。因此，SA@Cu/CBD 水凝胶可能是修复开放性骨缺损的一种有前途的候选材料。
