Activating Macrophage Continual Efferocytosis via Microenvironment Biomimetic Short Fibers for Reversing Inflammation in Bone Repair.

Efferocytosis-mediated inflammatory reversal plays a crucial role in bone repairing process. However, in refractory bone defects, the macrophage continual efferocytosis may be suppressed due to the disrupted microenvironment homeostasis, particularly the loss of apoptotic signals and overactivation of intracellular oxidative stress. In this study, we present a polydopamine-coated short fiber matrix containing biomimetic "apoptotic signals" to reconstruct the microenvironment and reactivate macrophage continual efferocytosis for inflammatory reversal and bone defect repair. The "apoptotic signals" (AM/CeO 2 ) are prepared using CeO 2 nanoenzymes with apoptotic neutrophil membrane coating for macrophage recognition and oxidative stress regulation. Additionally, a short fiber "biomimetic matrix" is utilized for loading AM/CeO 2 signals via abundant adhesion sites involving π-π stacking and hydrogen bonding interactions. Ultimately, the implantable apoptosis-mimetic nanoenzyme/short-fiber matrixes (PFS@AM/CeO 2 ), integrating apoptotic signals and biomimetic matrixes, are constructed to facilitate inflammatory reversal and reestablish pro-efferocytosis microenvironment. In vitro and in vivo data indicate that the microenvironment biomimetic short fibers could activate macrophage continual efferocytosis, leading to the suppression of overactivated inflammation. The enhanced repair of rat femoral defect further demonstrates the osteogenic potential of pro-efferocytosis strategy. We believe that the regulation of macrophage efferocytosis through microenvironment biomimetic materials could provide a new perspective for tissue repair. This article is protected by copyright. All rights reserved.