Terasaki Institute for Biomedical Innovations, Los Angeles, California 91367, United States.
Department of Surgery-Transplant and Mary & Dick Holland, Regenerative Medicine Program, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198, United States.
ACS Nano. 2024 Oct 15;18(41):28335-28348. doi: 10.1021/acsnano.4c10044. Epub 2024 Oct 2.
Diabetic foot ulcers (DFUs) are a significant challenge in the clinical care of diabetic patients, often necessitating limb amputation and compromising the quality of life and life expectancy of this cohort. Minimally invasive therapies, such as modular scaffolds, are at the forefront of current DFU treatment, offering an efficient approach for administering therapeutics that accelerate tissue repair and regeneration. In this study, we report a facile method for fabricating granular nanofibrous microspheres (NMs) with predesigned structures and porosities. The proposed technology combines electrospinning and electrospraying to develop a therapeutic option for DFUs. Specifically, porous NMs were constructed using electrospun poly(lactic--glycolic acid) (PLGA):gelatin short nanofibers, followed by gelatin cross-linking. These NMs demonstrated enhanced cell adhesion to human dermal fibroblasts (HDF) during an cytocompatibility assessment. Notably, porous NMs displayed superior performance owing to their interconnected pores compared to nonporous NMs. Cell-laden NMs demonstrated higher Young's modulus values than NMs without loaded cells, suggesting improved material resiliency attributed to the reinforcement of cells and their secreted extracellular matrix. Dynamic injection studies on cell-laden NMs further elucidated their capacity to safeguard loaded cells under pressure. In addition, porous NMs promoted host cell infiltration, neovascularization, and re-epithelialization in a diabetic mouse wound model, signifying their effectiveness in healing diabetic wounds. Taken together, porous NMs hold significant potential as minimally invasive, injectable treatments that effectively promote tissue integration and regeneration.
糖尿病足溃疡 (DFUs) 是糖尿病患者临床护理中的重大挑战，常导致肢体截肢，并降低该患者群体的生活质量和预期寿命。微创疗法，如模块化支架，是当前 DFU 治疗的前沿方法，为加速组织修复和再生的治疗提供了有效的途径。在本研究中，我们报告了一种制备具有预定结构和孔隙率的颗粒状纳米纤维微球 (NMs) 的简便方法。该技术结合了静电纺丝和静电喷雾，为 DFUs 提供了一种治疗选择。具体而言，使用静电纺丝的聚乳酸-羟基乙酸共聚物 (PLGA):明胶短纳米纤维构建多孔 NMs，然后进行明胶交联。在细胞相容性评估中，这些 NMs 表现出增强的人真皮成纤维细胞 (HDF) 细胞黏附性。值得注意的是，与非多孔 NMs 相比，多孔 NMs 由于其互连的孔而表现出更好的性能。载细胞的 NMs 的杨氏模量值高于未载细胞的 NMs，表明由于细胞及其分泌的细胞外基质的增强，材料的弹性得到了提高。对载细胞的 NMs 的动态注射研究进一步阐明了它们在压力下保护载细胞的能力。此外，多孔 NMs 促进了糖尿病小鼠伤口模型中的宿主细胞浸润、新血管生成和再上皮化，表明它们在治疗糖尿病伤口方面的有效性。总之，多孔 NMs 作为微创、可注射的治疗方法具有重要的潜力，可有效促进组织整合和再生。
