Affiliation:
1. Department of Plastic and Reconstructive Surgery Shanghai Ninth People's Hospital Shanghai JiaoTong University School of Medicine 639 Zhi Zao Ju Road Shanghai 200011 P. R. China
2. Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine 197 Ruijin 2nd Road Shanghai 200025 P. R. China
3. Laboratory of Key Technology and Materials in Minimally Invasive Spine Surgery Tongren Hospital Shanghai Jiao Tong University School of Medicine 1111 XianXia Road Shanghai 200336 P. R. China
Abstract
AbstractEfferocytosis, by phagocytosing and processing apoptotic cells in injured skin, directly influences the immune microenvironment. However, the comprehensive widespread inflammation and disrupted efferocytosis in injured skin cannot be effectively halted. Herein, “Grid Efferocytosis” strategy within injury site is proposed, which segments the inflammation regulatory into grid microdomains, and further rectifies intra‐grid immune microenvironment to accelerate tissue repair. GelMA/PLA/Laponite gridded fiber membranes (GPL) are custom‐designed via near‐field electrostatic printing, and then coated with HAMA‐PBA/EGCG hydrogel by photo‐crosslinking and dynamic borate bonding to form a composite fiber membrane (GPL‐E). Gridded modulation via GPL‐E confines the entire chaotic inflammatory microenvironment into controllable microinflammatory niches. Leveraging the hydrogel coating and boronic ester bond dissociation induced by microenvironmental glucose and reactive oxygen species, GPL‐E achieves dynamic anti‐glucose and anti‐oxidation within microdomains, reconstructing macrophage efferocytosis. Notably, the “grid efferocytosis” recruits repair cells into the grid by magnesium ion release triggered by Laponite exposure on fibers, and enhances endothelial cell vascularization by ≈2.5‐fold. In a mouse diabetic ischemic flap model, implantation of grid GPL‐E maintains flap‐to‐base fusion, attenuates inflammatory infiltration & spread, and improves blood perfusion for flap survival. This study demonstrates that “Grid Efferocytosis” rectifies the immune microenvironment, fostering tissue repair and regeneration.
Funder
National Natural Science Foundation of China