Luo Tong, Zhu Peijun, Li Shuai, Qin Maolin, Fang Zeyu, Wu Fangfang, Wu Qian, Lu Suhong, Zhang Yinhe, Chen Yuli, Zhou Junhua, Chen Daqing, Yang Liangliang, Zhang Hongyu
Affiliated Cixi Hospital, Wenzhou Medical University, Cixi, 315300, Zhejiang, China.
Department of Emergency, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China.
Mater Today Bio. 2025 Jun 14;33:101973. doi: 10.1016/j.mtbio.2025.101973. eCollection 2025 Aug.
Diabetic wounds represent a prevalent and challenging complication of diabetes, characterized by compromised immune function, chronic inflammation, oxidative stress, and impaired revascularization, all of which impede normal wound healing. Despite the high therapeutic potential of 3D stem cell spheroids, owing to their structural and functional advantages, the complex microenvironment encountered post-transplantation significantly diminishes their survival and efficacy. This study presents a novel therapeutic strategy that integrates three-dimensional adipose-derived stem cell spheroids (3D-ADSCs) with desferrioxamine-loaded mesoporous polydopamine nanoparticles (M@D), encapsulated within a gelatin methacrylamide (GelMA) hydrogel scaffold, creating a functional bio-composite. The M@D nanoparticles are designed to scavenge reactive oxygen species (ROS) and provide sustained release of desferrioxamine mesylate (DFO), thereby mitigating oxidative stress, fostering angiogenesis, and improving the local wound microenvironment. This enhanced environment significantly promotes the survival, paracrine activity, and regenerative capacity of 3D-ADSCs spheroids. In turn, these spheroids exert potent paracrine, anti-inflammatory, and immunomodulatory effects, pivotal in tissue repair. The synergistic interaction between M@D nanoparticles and 3D-ADSCs within the GelMA hydrogel not only alleviates oxidative stress-induced cellular damage but also enhances vascularization and nutrient supply, thereby accelerating diabetic wound healing. These results underscore the promising potential of combining cell therapy with material science to develop innovative approaches for diabetic wound management.
糖尿病伤口是糖尿病常见且具有挑战性的并发症，其特征为免疫功能受损、慢性炎症、氧化应激和血管再生受损，所有这些都会阻碍伤口正常愈合。尽管三维干细胞球因其结构和功能优势具有很高的治疗潜力，但移植后遇到的复杂微环境会显著降低其存活率和疗效。本研究提出了一种新的治疗策略，即将三维脂肪来源干细胞球（3D-ADSCs）与负载去铁胺的介孔聚多巴胺纳米颗粒（M@D）整合，封装在明胶甲基丙烯酰胺（GelMA）水凝胶支架中，形成一种功能性生物复合材料。M@D纳米颗粒旨在清除活性氧（ROS）并提供甲磺酸去铁胺（DFO）的持续释放，从而减轻氧化应激，促进血管生成，并改善局部伤口微环境。这种改善的环境显著促进了3D-ADSCs球的存活、旁分泌活性和再生能力。反过来，这些球发挥强大的旁分泌、抗炎和免疫调节作用，这对组织修复至关重要。GelMA水凝胶中M@D纳米颗粒与3D-ADSCs之间的协同相互作用不仅减轻了氧化应激诱导的细胞损伤，还增强了血管生成和营养供应，从而加速糖尿病伤口愈合。这些结果强调了将细胞疗法与材料科学相结合以开发糖尿病伤口管理创新方法的广阔前景。
