Tissue Engineering Research Group, Department of Anatomy & Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), 123 St. Stephen's Green, Dublin D02 YN77, Ireland.
Advanced Materials and BioEngineering Research (AMBER) Centre, RCSI and TCD, Dublin D02 PN40, Ireland.
ACS Appl Mater Interfaces. 2023 Apr 12;15(14):17444-17458. doi: 10.1021/acsami.2c18837. Epub 2023 Mar 31.
Chronic, nonhealing wounds in the form of diabetic foot ulcers (DFUs) are a major complication for diabetic patients. The inability of a DFU to heal appropriately leads to an open wound with a high risk of infection. Current standards of care fail to fully address either the underlying defective wound repair mechanism or the risk of microbial infection. Thus, it is clear that novel approaches are needed. One such approach is the use of multifunctional biomaterials as platforms to direct and promote wound healing. In this study, a biomimetic, bilayered antimicrobial collagen-based scaffold was developed to deal with the etiology of DFUs. An epidermal, antimicrobial collagen/chitosan film for the prevention of wound infection was combined with a dermal collagen-glycosaminoglycan scaffold, which serves to support angiogenesis in the wound environment and ultimately accelerate wound healing. Biophysical and biological characterization identified an 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide cross-linked bilayered scaffold to have the highest structural stability with similar mechanical properties to products on the market, exhibiting a similar structure to native skin, successfully inhibiting the growth and infiltration of and supporting the proliferation of epidermal cells on its surface. This bilayered scaffold also demonstrated the ability to support the proliferation of key cell types involved in vascularization, namely, induced pluripotent stem cell derived endothelial cells and supporting stromal cells, with early signs of organization of these cells into vascular structures, showing great promise for the promotion of angiogenesis. Taken together, the results indicate that the bilayered scaffold is an excellent candidate for enhancement of diabetic wound healing by preventing wound infection and supporting angiogenesis.
慢性、难以愈合的伤口，如糖尿病足溃疡（DFU），是糖尿病患者的主要并发症。DFU 无法适当愈合会导致开放性伤口，感染风险高。目前的护理标准既不能充分解决潜在的伤口修复机制缺陷问题，也不能解决微生物感染的风险。因此，显然需要新的方法。一种这样的方法是使用多功能生物材料作为平台来指导和促进伤口愈合。在这项研究中，开发了一种仿生的双层抗菌胶原基支架，以解决 DFU 的病因。一个表皮抗菌胶原/壳聚糖膜用于预防伤口感染，与真皮胶原糖胺聚糖支架相结合，以支持伤口环境中的血管生成，并最终加速伤口愈合。生物物理和生物学特性表明，一种 1-乙基-3-(3-(二甲基氨基)丙基)碳二亚胺交联的双层支架具有最高的结构稳定性，其机械性能与市场上的产品相似，具有类似于天然皮肤的结构，成功抑制 和支持表皮细胞在其表面的增殖。这种双层支架还表现出支持血管生成中关键细胞类型增殖的能力，即诱导多能干细胞衍生的内皮细胞和支持基质细胞，这些细胞早期有组织成血管结构的迹象，显示出促进血管生成的巨大潜力。总之，这些结果表明，双层支架是通过预防伤口感染和支持血管生成来增强糖尿病伤口愈合的优秀候选者。
