Das Subhamoy, Singh Gunjan, Majid Marjan, Sherman Michael B, Mukhopadhyay Somshuvra, Wright Catherine S, Martin Patricia E, Dunn Andrew K, Baker Aaron B
Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, 78731, USA.
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, 77555, USA.
Adv Healthc Mater. 2016 Sep;5(17):2248-60. doi: 10.1002/adhm.201600285. Epub 2016 Jul 6.
Chronic wounds represent a major healthcare and economic problem worldwide. Advanced wound dressings that incorporate bioactive compounds have great potential for improving outcomes in patients with chronic wounds but significant challenges in designing treatments that are effective in long-standing, nonhealing wounds. Here, an optimized wound healing gel was developed that delivers syndecan-4 proteoliposomes ("syndesomes") with fibroblast growth factor-2 (FGF-2) to enhance diabetic wound healing. In vitro studies demonstrate that syndesomes markedly increase migration of keratinocytes and fibroblasts isolated from both nondiabetic and diabetic donors. In addition, syndesome treatment leads to increased endocytic processing of FGF-2 that includes enhanced recycling of FGF-2 to the cell surface after uptake. The optimized syndesome formulation was incorporated into an alginate wound dressing and tested in a splinted wound model in diabetic, ob/ob mice. It was found that wounds treated with syndesomes and FGF-2 have markedly enhanced wound closure in comparison to wounds treated with only FGF-2. Moreover, syndesomes have an immunomodulatory effect on wound macrophages, leading to a shift toward the M2 macrophage phenotype and alterations in the wound cytokine profile. Together, these studies show that delivery of exogenous syndecan-4 is an effective method for enhancing wound healing in the long-term diabetic diseased state.
慢性伤口是全球范围内主要的医疗保健和经济问题。含有生物活性化合物的先进伤口敷料在改善慢性伤口患者的治疗效果方面具有巨大潜力，但在设计对长期不愈合伤口有效的治疗方法时面临重大挑战。在此，开发了一种优化的伤口愈合凝胶，其可递送含有成纤维细胞生长因子-2（FGF-2）的Syndecan-4蛋白脂质体（“Syndesomes”）以促进糖尿病伤口愈合。体外研究表明，Syndesomes显著增加从非糖尿病和糖尿病供体分离的角质形成细胞和成纤维细胞的迁移。此外，Syndesomes处理导致FGF-2的内吞加工增加，包括FGF-2摄取后向细胞表面的再循环增强。将优化的Syndesomes制剂掺入藻酸盐伤口敷料中，并在糖尿病ob/ob小鼠的夹板伤口模型中进行测试。结果发现，与仅用FGF-2处理的伤口相比，用Syndesomes和FGF-2处理的伤口愈合明显增强。此外，Syndesomes对伤口巨噬细胞具有免疫调节作用，导致向M2巨噬细胞表型转变并改变伤口细胞因子谱。总之，这些研究表明，递送外源性Syndecan-4是在长期糖尿病疾病状态下增强伤口愈合的有效方法。
