Injectable amino-modified poly-L-lactic acid microspheres/hyaluronic acid-based hydrogel composites for soft tissue fillers

Soft tissue fillers have received much attention for the treatment of skin aging and the restoration of missing or excised soft volumes. However, the development of fillers with both safety and applicability remains a challenge. This study presented a synergistic composite filler comprising aldehyde-modified hyaluronic acid (OHA), hydrazide-modified hyaluronic acid (NHA), amino-modified poly-L-lactic acid microspheres (NPLLA), and antioxidant copper peptide. The hydrogel formed in situ via Schiff base reaction exhibited excellent mechanical properties and immediate filling effect. The amino-modified PLLA microspheres were less likely to agglomerate, avoiding the occurrence of adverse reactions and further enhancing the mechanical properties of the filler. The timed-release platform provided protection for copper peptide stability, scavenged reactive oxygen species during the fibrotic encapsulation phase, and synergistically promoted collagen deposition. In a nude mice skin aging model, hydrogels stimulated collagen production through the TGF-β/Smad signaling pathway with good long-term filler efficacy. Therefore, NPLLA microspheres/hyaluronic acid-based composite hydrogels exhibit great potential as injectable soft tissue fillers.