National Centre for Cell Science, NCCS Complex, University of Pune Campus, Ganeshkhind, Pune, Maharashtra, India.
PLoS One. 2013 Jul 26;8(7):e69960. doi: 10.1371/journal.pone.0069960. Print 2013.
Diabetes mellitus (DM)-induced endothelial progenitor cell (EPC) dysfunction causes impaired wound healing, which can be rescued by delivery of large numbers of 'normal' EPCs onto such wounds. The principal challenges herein are (a) the high number of EPCs required and (b) their sustained delivery onto the wounds. Most of the currently available scaffolds either serve as passive devices for cellular delivery or allow adherence and proliferation, but not both. This clearly indicates that matrices possessing both attributes are 'the need of the day' for efficient healing of diabetic wounds. Therefore, we developed a system that not only allows selective enrichment and expansion of EPCs, but also efficiently delivers them onto the wounds. Murine bone marrow-derived mononuclear cells (MNCs) were seeded onto a PolyCaprolactone-Gelatin (PCG) nano-fiber matrix that offers a combined advantage of strength, biocompatibility wettability; and cultured them in EGM2 to allow EPC growth. The efficacy of the PCG matrix in supporting the EPC growth and delivery was assessed by various in vitro parameters. Its efficacy in diabetic wound healing was assessed by a topical application of the PCG-EPCs onto diabetic wounds. The PCG matrix promoted a high-level attachment of EPCs and enhanced their growth, colony formation, and proliferation without compromising their viability as compared to Poly L-lactic acid (PLLA) and Vitronectin (VN), the matrix and non-matrix controls respectively. The PCG-matrix also allowed a sustained chemotactic migration of EPCs in vitro. The matrix-effected sustained delivery of EPCs onto the diabetic wounds resulted in an enhanced fibrosis-free wound healing as compared to the controls. Our data, thus, highlight the novel therapeutic potential of PCG-EPCs as a combined 'growth and delivery system' to achieve an accelerated fibrosis-free healing of dermal lesions, including diabetic wounds.
糖尿病（DM）引起的内皮祖细胞（EPC）功能障碍导致伤口愈合受损，可以通过将大量“正常”EPC 递送到这些伤口上来挽救。这里的主要挑战是（a）需要大量的 EPC，（b）将它们持续递送到伤口上。目前大多数可用的支架要么作为细胞递送来被动使用，要么允许附着和增殖，但不能同时进行。这清楚地表明，具有这两种特性的基质是糖尿病伤口有效愈合的“当务之急”。因此，我们开发了一种系统，不仅可以选择性地富集和扩增 EPC，还可以有效地将其递送到伤口上。将鼠骨髓来源的单核细胞（MNC）接种到聚己内酯-明胶（PCG）纳米纤维基质上，该基质具有强度、生物相容性、润湿性的综合优势；并在 EGM2 中培养它们，以允许 EPC 生长。通过各种体外参数评估 PCG 基质在支持 EPC 生长和递送上的功效。通过将 PCG-EPC 局部应用于糖尿病伤口来评估其在糖尿病伤口愈合中的功效。与聚 L-乳酸（PLLA）和 Vitronectin（VN）相比，PCG 基质促进了 EPC 的高水平附着，并增强了它们的生长、集落形成和增殖，而不会影响其活力，PCG 基质分别是基质和非基质对照。PCG 基质还允许 EPC 在体外进行持续的趋化迁移。PCG 基质将 EPC 持续递送到糖尿病伤口上，与对照组相比，促进了无纤维化的伤口愈合。因此，我们的数据突出了 PCG-EPC 作为一种联合“生长和递药系统”的新的治疗潜力，以实现皮肤病变（包括糖尿病伤口）的无纤维化加速愈合。
