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Improved drug delivery and accelerated diabetic wound healing by chondroitin sulfate grafted alginate-based thermoreversible hydrogels
Biomaterials Advances ( IF 5.5 ) Pub Date : 2021-05-14 , DOI: 10.1016/j.msec.2021.112169
Syed Ahmed Shah , Muhammad Sohail , Shujaat Ali Khan , Mubeen Kousar

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 (1H 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.



中文翻译:

硫酸软骨素接枝藻酸盐基热可逆水凝胶改善药物递送并加速糖尿病伤口愈合

为了有效地促进糖尿病伤口的修复,高度优选具有多功能可调性质的可注射水凝胶,包括生物相容性,抗氧化,抗细菌和/或抗感染,以有效地促进糖尿病伤口的修复,其发展仍然是一个挑战。在这项研究中,我们报道了使用硫酸钙软骨素和海藻酸钠(SA)为主的可注射水凝胶,其中使用的溶剂浇铸方法装有姜黄素,可增强再上皮化,增加血管生成和伤口微环境中的胶原沉积,从而支持愈合级联反应。利用核磁共振证实了硫酸软骨素接枝海藻酸盐(CS-Alg- g -PF127)水凝胶的物理相互作用和自组装(11 H NMR)和傅立叶变换红外光谱(FT-IR),并通过成纤维细胞活力测定证实了细胞相容性。Masson的三色(MT)以及苏木精和曙红(H&E)结果显示,空白硫酸软骨素接枝海藻酸盐(CS-Alg- g -PF127)和CUR负载的CS-Alg- g与其他治疗组相比,-PF127水凝胶具有良好的组织再生能力,并显示出增强的伤口愈合能力。通过药物释放研究评估了CUR从可注射水凝胶中的控制释放,并使用高效液相色谱(HPLC)展示了平均停留时间(MRT)和曲线下面积(AUC)增加到分别为16.18 h和203.64±30.1μg/ mL * h。使用3个T3-L1成纤维细胞对可注射水凝胶进行细胞毒性分析,并通过皮下注射24小时进行组织学评估,评估其体内毒性,证实了CUR负载的CS-Alg- g -PF127水凝胶具有良好的生物相容性。有趣的是,体内结果 注射水凝胶的伤口愈合显示出成纤维细胞样细胞的上调,胶原蛋白的沉积以及刺激皮肤-表皮连接的分化的角质形成细胞,这可能表明它们是切除伤口愈合模型的潜在候选者。

更新日期:2021-05-19
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