Department of Pharmacy, COMSATS University, Islamabad, Abbottabad Campus, 22010, Pakistan.
Department of Pharmacy, COMSATS University, Islamabad, Abbottabad Campus, 22010, Pakistan.
Mater Sci Eng C Mater Biol Appl. 2021 Jul;126:112169. doi: 10.1016/j.msec.2021.112169. Epub 2021 May 14.
Injectable hydrogels with multifunctional tunable properties comprising biocompatibility, anti-oxidative, anti-bacterial, and/or anti-infection are highly preferred to efficiently promote diabetic wound repair and its development remains a challenge. In this study, we report chondroitin sulphate (CS) and sodium alginate (SA)-based injectable hydrogel using solvent casting method loaded with curcumin that could potentiate reepithelization, increase angiogenesis, and collagen deposition at wound microenvironment to endorse healing cascade. The physical interaction and self-assembly of chondroitin sulfate grafted alginate (CS-Alg-g-PF127) hydrogel were confirmed using nuclear magnetic resonance (H NMR) and Fourier transformed infrared spectroscopy (FT-IR), and cytocompatibility was confirmed by fibroblast viability assay. The Masson's trichrome (MT) and hematoxylin and eosin (H&E) results revealed that blank chondroitin sulfate grafted alginate (CS-Alg-g-PF127) and CUR loaded CS-Alg-g-PF127 hydrogel had promising tissue regenerative ability, and showing enhanced wound healing compared to other treatment groups. The controlled release of CUR from injectable hydrogel was evaluated by drug release studies and pharmacokinetic profile (PK) using high-performance liquid chromatography (HPLC) that exhibited the mean residence time (MRT) and area under the curve (AUC) was increased up to 16.18 h and 203.64 ± 30.1 μg/mL*h, respectively. Cytotoxicity analysis of the injectable hydrogels using 3 T3-L1 fibroblasts cells and in vivo toxicity evaluated by subcutaneous injection for 24 h followed by histological examination, confirmed good biocompatibility of CUR loaded CS-Alg-g-PF127 hydrogel. Interestingly, the results of in vivo wound healing by injectable hydrogel showed the upregulation of fibroblasts-like cells, collagen deposition, and differentiated keratinocytes stimulating dermo-epidermal junction, which might endorse that they are potential candidates for excisional wound healing models.
具有多功能可调特性的可注射水凝胶,包括生物相容性、抗氧化、抗菌和/或抗感染,非常适合有效促进糖尿病伤口修复,但其发展仍然是一个挑战。在这项研究中,我们报告了一种基于硫酸软骨素(CS)和海藻酸钠(SA)的可注射水凝胶,采用溶剂浇铸法负载姜黄素,可增强再上皮化、增加血管生成和胶原蛋白在伤口微环境中的沉积,以促进愈合级联反应。使用核磁共振(NMR)和傅里叶变换红外光谱(FT-IR)证实了硫酸软骨素接枝海藻酸钠(CS-Alg-g-PF127)水凝胶的物理相互作用和自组装,通过成纤维细胞活力测定证实了细胞相容性。马松三色(MT)和苏木精和伊红(H&E)结果表明,空白硫酸软骨素接枝海藻酸钠(CS-Alg-g-PF127)和负载 CUR 的 CS-Alg-g-PF127 水凝胶具有有前途的组织再生能力,与其他治疗组相比,显示出增强的伤口愈合能力。通过高效液相色谱法(HPLC)进行药物释放研究和药代动力学(PK)评估,从可注射水凝胶中控制 CUR 的释放,结果表明平均驻留时间(MRT)和曲线下面积(AUC)分别增加到 16.18 小时和 203.64±30.1μg/mL*h。使用 3T3-L1 成纤维细胞细胞进行可注射水凝胶的细胞毒性分析,并通过皮下注射 24 小时后进行组织学检查评估体内毒性,证实负载 CUR 的 CS-Alg-g-PF127 水凝胶具有良好的生物相容性。有趣的是,可注射水凝胶的体内伤口愈合结果表明,成纤维细胞样细胞的上调、胶原蛋白沉积和分化的角蛋白细胞刺激真皮-表皮连接,这可能表明它们是切创伤口愈合模型的潜在候选物。
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