Dual stimulus-responsive dECM cryogel sequentially regulate bone microenvironment for one-step surgical therapy of...

Combining disinfection and bone regeneration in a one-step treatment is of significant clinical importance for chronic osteomyelitis, yet it remains a considerable challenge. To address this, we developed a dual stimulus-responsive decellularized extracellular matrix (dECM) cryogel (GC-dECM@CPN). The cryogel is composed of methacrylate gelatin (GelMA), carboxymethyl chitosan (CMCS), dECM, and temperature-sensitive phase-transition copper peroxide nanoparticles (CPNs). During the infection phase of chronic osteomyelitis, the cryogel exhibits a strong photothermal conversion efficiency under near-infrared (NIR) light irradiation, triggering the release of CPNs to perform chemodynamic therapy (CDT) in the acidic, infected environment. This process enhances macrophage polarization toward the M1 phenotype, promoting the phagocytosis of residual bacteria. Following bacterial eradication, the dECM within the cryogel facilitates the differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts while reprogramming macrophages into the M2 phenotype, thereby establishing a conducive environment for bone regeneration. The GC-dECM@CPN cryogel exhibited desirable therapeutic efficacy in both in vitro and in vivo studies, with critical stages of chronic osteomyelitis-including early infection, initial bone regeneration, and recovery-investigated and discussed in detail. This study introduces an innovative dual stimulus-responsive dECM cryogel that effectively treats chronic osteomyelitis through a one-step surgical approach, offering valuable insights for clinical therapeutic strategies in this field.