Lee Yu-Hsiang, Hong Yi-Ling, Wu Tai-Li
Department of Biomedical Sciences and Engineering, National Central University, Taoyuan City, Taiwan; Department of Chemical and Materials Engineering, National Central University, Taoyuan City, Taiwan.
Department of Biomedical Sciences and Engineering, National Central University, Taoyuan City, Taiwan.
Mater Sci Eng C Mater Biol Appl. 2021 Jan;118:111385. doi: 10.1016/j.msec.2020.111385. Epub 2020 Aug 13.
Diabetic foot ulcer, one of the most common diabetic complications, is a progressive wound occurred on the skin with irregularly delayed wound healing rate due to impaired metabolism and weak immune responses. Such chronic wound remains a serious healthcare burden to the diabetics since it is often associated with high risk of limb loss due to amputation and leads to a reduced survival consequently. To improve the efficiency of diabetic wound healing, a synthetic chitosan-based composite hydrogel named SNPCHG incorporating silver ions (Ag) and nanoparticle-encapsulated epidermal growth factor (EGF) was developed in this study. The optimal effective dosages of 24-mM Ag and 60-μg mL EGF for the SNPCHG manufacture were first determined based on the results of antibacterial, cytotoxicity, and cell growth examinations. We then characterized the optimized SNPCHG and found that the composite hydrogel was able to provide sustained release of Ag and EGF, and exhibited a significantly higher hydration capacities, including the swelling degree and equilibrium water content, in PBS than those in deionized water, showing that the developed SNPCHG is highly applicable in the ion-rich environment such as chronic wound site. According to the results of in vivo study using diabetic rats, the one with SNPCHG exhibited a markedly enhanced wound healing effect compared with the other settings since day 3, and may reach a degree of wound closure of 97% at day 14 that was 7.4% (P < 0.05) and 18.9% (P < 0.05) higher than the values gained from the groups with the commercial dressing HeraDerm and gauze, respectively. Moreover, the wound treated with the SNPCHG exhibited thorough re-epithelization, sufficient collagen deposition, and accelerated collagen maturation confirmed by the histological analysis. Taken all together, we anticipate that the SNPCHG is highly advantageous for use in the clinical diabetic/chronic wound treatment.
糖尿病足溃疡是最常见的糖尿病并发症之一，是一种发生在皮肤上的进行性伤口，由于新陈代谢受损和免疫反应减弱，伤口愈合速度不规则且延迟。这种慢性伤口仍然是糖尿病患者严重的医疗负担，因为它通常与因截肢导致的肢体丧失高风险相关，从而导致生存率降低。为了提高糖尿病伤口愈合的效率，本研究开发了一种名为SNPCHG的基于壳聚糖的合成复合水凝胶，其中含有银离子（Ag）和纳米颗粒包裹的表皮生长因子（EGF）。基于抗菌、细胞毒性和细胞生长检查的结果，首先确定了用于制造SNPCHG的24 mM Ag和60 μg/mL EGF的最佳有效剂量。然后我们对优化后的SNPCHG进行了表征，发现复合水凝胶能够实现Ag和EGF的持续释放，并且在PBS中表现出比去离子水中显著更高的水合能力，包括溶胀度和平衡含水量，这表明所开发的SNPCHG在诸如慢性伤口部位等富含离子的环境中具有高度适用性。根据使用糖尿病大鼠的体内研究结果，自第3天起，使用SNPCHG的大鼠与其他组相比，伤口愈合效果明显增强，在第14天伤口闭合程度可能达到97%，分别比使用商业敷料HeraDerm和纱布的组高出7.4%（P<0.05）和18.9%（P<0.05）。此外，经组织学分析证实，用SNPCHG处理的伤口表现出完全的上皮再形成、足够的胶原蛋白沉积和加速的胶原蛋白成熟。综上所述，我们预计SNPCHG在临床糖尿病/慢性伤口治疗中具有高度优势。
