Stem Cell Membrane-coated Microribbon Scaffolds Induce Regenerative Innate and Adaptive Immune Responses in a Critical-Size Cranial Bone Defect Model.

Naturally-derived cell membranes have shown great promise in functionalizing nanoparticles to enhance biointerfacing functions for drug delivery applications. However, its potential for functionalizing macroporous scaffolds to enhance tissue regeneration in vivo remains unexplored. Engineering scaffolds with immunomodulatory functions represents an exciting strategy for tissue regeneration but is largely limited to soft tissues. Critical sized bone defects cannot heal on its own, and the role of adaptive immune cells in scaffold-mediated healing of cranial bone defects remain largely unknown. Here we report mensenchymal stem cell membrane (MSCM)-coated microribbon (μRB) scaffolds for treating critical size cranial bone defects via targeting immunomodulation. Confocal imaging and proteomic analyses were used to confirm successful coating and characterize the compositions of cell membrane coating. We demonstrate MSCM coating promotes Mφ polarization towards regenerative phenotype, induces CD8+ T cell apoptosis, and enhances regulatory T cell differentiation in vitro and in vivo. MSCM primed with pro-inflammatory cytokines enhances regenerative immune response and promotes MSC osteogenesis. When combined with a low dosage of BMP-2, primed MSCM coating further accelerates bone regeneration and suppresses inflammation. These results establish cell membrane-coated microribbon scaffolds as a promising strategy for treating critical size bone defects via immunomodulation. The platform may be broadly used with different cell membranes and scaffolds to enhance regeneration of multiple tissue types. This article is protected by copyright. All rights reserved.