An injectable PLCL/CaHA microsphere composite gel for enhanced skin regeneration.

Efficient skin regeneration remains a clinical challenge due to the complex biological processes involved and the limitations of existing wound dressings, including biological inertness and inadequate biodegradability. Herein, we developed an injectable composite gel consisting of PLCL/CaHA composite microspheres followed by integration into a CMC/mannitol hydrogel carrier, which enables uniform dispersion of CaHA nanoparticles within the PLCL matrix-analogous to a "nuts-in-chocolate" structure. Structural characterization confirmed that CaHA nanoparticles were homogeneously embedded within the porous PLCL microspheres, forming an integrated composite architecture. In vitro, the PLCL/CaHA composite significantly enhanced L929 fibroblast migration, upregulated ECM-related gene expression, and promoted fibronectin deposition and Ki67-positive proliferation compared to controls. In a murine full-thickness wound model, treatment with PLCL/CaHA accelerated wound closure, enhanced angiogenesis with improved vessel maturation, and induced M2 macrophage polarization, leading to superior tissue regeneration. These findings demonstrate that this structurally engineered composite creates a favorable regenerative microenvironment and represents a promising platform for soft tissue repair.