High performance injectable PLLA/BG composite microspheres in aging skin regeneration

Poly-L-lactic acid (PLLA) microspheres have been successfully commercialized for skin rejuvenation. However, the inherent material properties, notably their hydrophobic surface and the acidic byproducts generated during degradation, have the potential to incite inflammatory responses and compromise long-term efficacy in tissue regeneration. In order to overcome these limitations, integrating biodegradable polymers with bioactive components are highly desirable to synergistically improve biocompatibility and actively stimulate tissue regeneration. In this study, we engineered novel composite microspheres that integrate PLLA with bioactive glass (BG). In vitro, PLLA/BG composite microspheres functioned as potent biomimetic cues, dramatically boosting cell biological behaviors of human foreskin fibroblasts (HFFs). Furthermore, the microspheres upregulated the expression of critical extracellular matrix (ECM) proteins, which underscores their potential to drive skin regeneration, and orchestrated a pro-regenerative response by upregulating key signaling factors, including transforming growth factor β1 (TGF-β1) and PDZ and LIM domain 5 (PDLIM5). The microspheres effectively polarized macrophages toward the pro-regenerative M2 phenotype and enhanced angiogenesis. In vivo experiments using a wrinkle-induced mouse model demonstrated that PLLA/BG composite microspheres significantly suppressed wrinkle formation, enhanced the deposition of ECM proteins, and stimulated new blood vessel formation. Collectively, our results established that PLLA/BG composite microspheres could modulate the skin microenvironment and achieve rejuvenation of aging skin.