Inflammation after traumatic injury or surgical intervention is both a protective tissue response leading to regeneration and a potential cause of wound complications. One potentially successful strategy to harness to pro-regenerative roles of host inflammation is the localized delivery of bioactive materials to induce immune suppressive cellular responses by cells responding to injury. In this study, we designed a fully synthetic poly (ethylene) glycol (PEG)-based hydrogel to release the specialized pro-resolving lipid mediator aspirin-triggered resolvin-D1 (AT-RvD1) and recombinant human interleukin 10 (IL-10). We utilized a unique side-by-side internally controlled implant design wherein bioactive hydrogels were implanted adjacent to control hydrogels devoid of immune modulatory factors in the dorsal skinfold window chamber. We also explored single-immune cell data with unsupervised approaches such as SPADE. First, we show that RGD-presenting hydrogel delivery results in enhanced immune cell recruitment to the site of injury. We then use intra-vital imaging to assess cellular recruitment and microvascular remodeling to show an increase in the caliber and density of local microvessels. Finally, we show that the recruitment and re-education of mononuclear phagocytes by combined delivery IL-10 and AT-RvD1 localizes immune suppressive subsets to the hydrogel, including CD206⁺ macrophages (M2a/c) and IL-10 expressing dendritic cells in the context of chronic inflammation following surgical tissue disruption. These data demonstrate the potential of combined delivery on the recruitment of regenerative cell subsets involved in wound healing complications.

创伤性损伤或手术干预后的炎症既是导致再生的保护性组织反应，也是伤口并发症的潜在原因。利用宿主炎症的促再生作用的一种潜在成功策略是局部递送生物活性材料，以诱导细胞对损伤作出反应而产生免疫抑制细胞反应。在这项研究中，我们设计了一种全合成的聚乙二醇 (PEG) 水凝胶，用于释放专门的促溶解脂质介质阿司匹林触发的溶解素-D1 (AT-RvD1) 和重组人白细胞介素 10 (IL-10) 。我们采用了独特的并排内部控制植入物设计，其中生物活性水凝胶被植入到背侧皮褶窗室中与不含免疫调节因子的对照水凝胶相邻的位置。我们还使用 SPADE 等无监督方法探索了单免疫细胞数据。首先，我们表明 RGD 呈递的水凝胶递送可增强免疫细胞向损伤部位的募集。然后，我们使用活体成像来评估细胞募集和微血管重塑，以显示局部微血管的口径和密度的增加。最后，我们表明，通过联合递送 IL-10 和 AT-RvD1 来招募和再教育单核吞噬细胞，将免疫抑制子集定位到水凝胶中，包括 CD206 ⁺巨噬细胞 (M2a/c) 和表达 IL-10 的树突状细胞。手术组织破坏后慢性炎症的背景。这些数据证明了联合递送在招募参与伤口愈合并发症的再生细胞亚群方面的潜力。