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

초록

Background/Aim: 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. Materials and Methods: 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. Results: 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. Conclusion: 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.

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