A Fibrous–Porous Microsphere-Based Composite Filler for Synchronized Immediate and Long-Term Soft Tissue Restoration

Current injectable fillers often suffer from a transient efficacy and insufficient early stage improvement. To address this, we developed a composite dermal filler consisting of hyaluronic acid (HA) and poly-L-lactic acid-methoxypolyethyleneglycol (PLLA-mPEG) microspheres with a unique fibrous porous structure. This distinctive architecture enabled a rapid initial release of lactic acid, effectively accelerating early cell proliferation and fundamentally overcoming the challenge of poor initial skin improvement. In a rat model, the composite filler demonstrated superior performance by orchestrating a pro-regenerative microenvironment, eliciting controlled macrophage infiltration, upregulating TGF-β expression, and significantly stimulating endogenous collagen regeneration, which leads to sustained volume restoration. By ingeniously coupling the instant filling effect of HA with the structurally enhanced bioactive function of PLLA-mPEG microspheres, this composite filler represents a breakthrough strategy that synchronizes immediate correction with long-term tissue remodeling, holding great promise for treating skin laxity and soft tissue defects.