Hybrid cell membrane coating orchestrates foreign-body reactions, anti-adhesion, and pro-regeneration in abdominal wall reconstruction

Abstract

Tension-free synthetic meshes are the clinical standard for hernia repair, but they often trigger immune response-mediated complications such as severe foreign-body reactions (FBR), visceral adhesions, and fibrotic healing, increasing the risk of recurrence. Herein, we developed a hybrid cell membrane coating for macroscale mesh fibers that acts as an immune orchestrator, capable of balancing immune responses with tissue regeneration. Cell membranes derived from red blood cells (RBCs) and platelets (PLTs) were covalently bonded to fiber surfaces using functionalized-liposomes and click chemistry. The fusion of clickable liposomes with cell membranes significantly improved coating efficiency, coverage uniformity, and in vivo stability. Histological and flow cytometric analyses of subcutaneous implantation in rats and mice demonstrated significant biofunctional heterogeneity among various cell membrane coatings in FBR. Specifically, the RBC-PLT-liposome hybrid cell membrane coating markedly mitigated FBR, facilitated host cell infiltration, and promoted M2-type macrophage polarization. Importantly, experimental results of abdominal wall defect repairs in rats indicate that the hybrid cell membrane coating effectively prevented visceral adhesions, promoted muscle regenerative healing, and enhanced the recruitment of Pax7⁺/MyoD⁺ muscle satellite cells. Our findings suggest that the clickable hybrid cell membrane coating offers a promising approach to enhance clinical outcomes of hernia mesh in abdominal wall reconstruction.