Abstract：
Diabetic wounds are characterized by the disruption and cessation of essential healing stages, which include hemostasis, inflammation, proliferation, and remodeling. However, traditional treatments for diabetic wounds concentrate on individual stages of the healing process. Herein, this study utilizes mask-mediated sequential polymerization and varied cross-linking techniques to develop dual-modular microneedles (MNs) with fast- and slow-module, exhibiting varying degradation rates tailored for the full spectrum of diabetic wound healing. First, MNs incorporating calcium ions and dopamine synergistically promote rapid hemostasis. Second, fast-module physically cross-linked MNs rapidly D-mannose/dopamine-enhanced tripolyphosphate-quaternized chitosan (mDTC) nanoparticles (NPs) loaded with microRNA-147 (miRNA-147) to manage inflammation and oxidative stress in diabetic wounds. Additionally, dopamine in these NPs enhances their internalization and safeguards miRNA-147 from oxidative stress and RNase degradation. Finally, slow-module chemically cross-linked MNs facilitate the continuous release of deferoxamine (DFO) and dopamine, accelerating angiogenesis and tissue regeneration during the proliferation and remodeling stages. Manganese/dopamine-enhanced calcium peroxide NPs within the MNs initiate a blast-like generation of oxygen bubbles, not only enhancing the delivery of miRNA-mDTC NPs and DFO but also alleviating tissue hypoxia. Consequently, dual-modular MNs are instrumental in promoting rapid and complete healing of diabetic wounds through all stages of healing.
摘要：
糖尿病伤口的特点是基本愈合阶段的中断和停止，其中包括止血，炎症,扩散,和重塑。然而,糖尿病伤口的传统治疗集中在愈合过程的各个阶段。在这里，本研究利用掩模介导的顺序聚合和各种交联技术来开发具有快速和慢速模块的双模块微针（MN），表现出针对糖尿病伤口愈合的全谱定制的不同降解速率。首先,掺入钙离子和多巴胺的MN协同促进快速止血。第二,快速模块物理交联的MN快速D-甘露糖/多巴胺增强的三聚磷酸盐季铵化壳聚糖（mDTC）纳米颗粒（NP）负载有microRNA-147（miRNA-147），以管理糖尿病伤口中的炎症和氧化应激。此外,这些NPs中的多巴胺增强其内在化并保护miRNA-147免受氧化应激和RNase降解。最后,慢模块化学交联的MN促进去铁胺（DFO）和多巴胺的连续释放，在增殖和重塑阶段加速血管生成和组织再生。MNs内的锰/多巴胺增强的过氧化钙NPs引发类似爆炸的氧气气泡生成，不仅增强miRNA-mDTCNP和DFO的递送，而且减轻组织缺氧。因此,双模块MNs有助于通过愈合的所有阶段促进糖尿病伤口的快速和完全愈合。
