Polyhydroxyalkanoate Microspheres Promote Skin Regeneration by Activating the MYBL2 Transcription Factor

Fibroblast-mediated decreased collagen synthesis is a key aspect of skin aging. Polyhydroxyalkanoate (PHA) materials have established clinical biocompatibility; however, the direct mechanisms of PHA microspheres on fibroblast-mediated skin rejuvenation remain unexplored. We aimed to investigate the impact of PHA microspheres on collagen production and its underlying molecular pathways. The microspheres demonstrated high biocompatibility, promoting human fibroblast proliferation in vitro and showing robust systemic safety in a rat model. In vivo, PHA microsphere injection significantly increased epidermal thickness and the expression of collagen I and III. Mechanistically, PHA microspheres improved mitochondrial function, as evidenced by elevated ATP production. MYBL2 was identified as a key transcriptional regulator; its knockdown attenuated fibroblast proliferation, collagen synthesis, and mitochondrial function. Importantly, PHA stimulation failed to rescue this effect, confirming that MYBL2 is required for the observed regeneration. In summary, we demonstrate that PHA microspheres drive fibroblast proliferation and collagen synthesis by upregulating MYBL2 and enhancing mitochondrial function. These findings provide a theoretical basis for the application of PHA microspheres as a collagen stimulant for skin rejuvenation.