Department of Anesthesia, the Third Xiangya Hospital of Central South University, Changsha, 410013, China.
Biomater Sci. 2020 Nov 21;8(22):6337-6349. doi: 10.1039/d0bm00999g. Epub 2020 Oct 7.
Chronic diabetic wounds, which are associated with persistent inflammation and impaired angiogenesis, occur frequently in diabetic patients. Some studies have shown that separate administration of vascular endothelial growth factor (VEGF) or stromal cell derived factor 1α (SDF-1α) exhibited a therapeutic effect in promoting angiogenesis in the wound healing process. In this study, a collagen membrane is prepared as a drug delivery scaffold to investigate whether combined administration of SDF-1α and VEGF has a synergistic therapeutic effect on diabetic wound healing. We specifically fused a collagen-binding domain (CBD) with SDF-1α and VEGF separately, and sustained release of the two recombinant proteins from the collagen scaffold is successfully observed. Meanwhile, when a CBD-VEGF and CBD-SDF-1α co-modified scaffold is implanted in a diabetic rat skin wound model, it not only shows a synergistic effect in facilitating angiogenesis but also reduces inflammation in the short-term. Moreover, long-term results reveal that the co-modified scaffold is also able to enhance rapid wound healing, promote blood vessel regeneration, and assist cell proliferation, re-epithelialization and extracellular matrix accumulation. Taken together, our study indicates that the CBD-VEGF and CBD-SDF-1α co-modified scaffold helps in quick recovery from diabetic wounds by coordinating angiogenesis and inflammation.
慢性糖尿病性伤口常发生于糖尿病患者,其与持续的炎症和受损的血管生成有关。一些研究表明,血管内皮生长因子(VEGF)或基质细胞衍生因子 1α(SDF-1α)的单独给药在促进伤口愈合过程中的血管生成方面具有治疗作用。在这项研究中,我们制备了胶原膜作为药物递送支架,以研究 SDF-1α和 VEGF 的联合给药是否对糖尿病伤口愈合具有协同治疗作用。我们分别将胶原结合域(CBD)与 SDF-1α和 VEGF 融合,并成功观察到两种重组蛋白从胶原支架中的持续释放。同时,当将 CBD-VEGF 和 CBD-SDF-1α共修饰的支架植入糖尿病大鼠皮肤伤口模型中时,它不仅在促进血管生成方面表现出协同作用,而且在短期内还减轻了炎症。此外,长期结果表明,共修饰的支架还能够促进快速伤口愈合,促进血管再生,并协助细胞增殖、再上皮化和细胞外基质积累。总之,我们的研究表明,CBD-VEGF 和 CBD-SDF-1α 共修饰的支架通过协调血管生成和炎症有助于糖尿病伤口的快速恢复。