PLLA and PDLLA Fillers: Linking Crystallinity and Mechanical Stability to Aggregation, Redispersion, and Collagen...

Poly lactic acid microsphere fillers stimulate neocollagenesis, but aggregation can yield heterogeneous remodeling. We compared poly-L-lactic acid (PLLA)- and poly-D,L-lactic acid (PDLLA)-based fillers to connect stereochemistry with microsphere stability, dispersion, and in vivo outcomes.

Poly lactic acid/sodium hyaluronate composite fillers were analyzed by scanning electron microscopy, nuclear magnetic resonance, differential scanning calorimetry, and micro-compression. Dispersion-aggregation-redispersion in saline was quantified over 3 days by optical microscopy with circularity-based analysis. In SKH mice, 100 μl filler was injected subcutaneously. Projection volume was measured at baseline (day 0) and at 2, 4, 8, and 12 weeks post-injection using phase-shift rapid in vivo measurement of skin (PRIMOS). Tissue response was observed at the same time points using hematoxylin and eosin, Masson's trichrome, and macrophage immunofluorescence.

PLLA microspheres remained discrete after saline dispersion and excipient removal, whereas PDLLA particles deformed and collapsed into compact clusters. PLLA particles (median 49.10 μm) were larger than PDLLA particles (median=19.85 μm) and showed semicrystalline differential scanning calorimetry features (glass transition temperature=60.88°C, cold crystallization temperature=94.2°C, melting temperature=169.18°C), while PDLLA was predominantly amorphous. PDLLA formed larger, poorly re-dispersible aggregates (median cluster=458.06 μm) than PLLA (median cluster=380.02 μm). In vivo, volume declined through week 4 then recovered. PLLA rebounded more uniformly with greater collagen area and weaker inflammatory and macrophage signals than PDLLA.

PLLA crystallinity and mechanical robustness support re-dispersibility and more homogeneous collagen remodeling, whereas PDLLA aggregation is linked to heightened inflammation and reduced collagen deposition. Collectively, these findings suggest that maintaining microsphere integrity and dispersion is a key, actionable determinant of more uniform biostimulatory outcomes in PLA-based fillers.