Geara Jennifer, Luo Lihua, Parlak Onur, Sommar Pehr, Xu Landén Ning
Dermatology and Venereology Division, Department of Medicine (Solna), Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
J Biomed Mater Res A. 2025 Nov;113(11):e38017. doi: 10.1002/jbm.a.38017.
Skin aging is marked by fibroblast decline and extracellular matrix (ECM) degradation, prompting the widespread use of poly-L-lactic acid (PLLA) dermal injectables for activating fibroblasts, stimulating neocollagenesis, and rejuvenating the skin. However, current PLLA formulations show variable efficacy and may trigger undesirable inflammatory responses. In this study, we compared two different PLLA formulations -one containing novel microspherical PLLA (PLLA-LASYNPRO) and the other containing a microflake-like PLLA -to assess their differing effects on human dermal fibroblasts and skin tissue. The results show that PLLA microspheres promote fibroblast migration, ECM synthesis, and wound contraction, while PLLA microflakes inhibit proliferation and elicit inflammatory gene expression. Transcriptomic profiling reveals that PLLA microspheres upregulate genes involved in fat cell differentiation and energy metabolism, with minimal immune activation. In contrast, PLLA microflakes trigger immune pathways and suppress regenerative signals. Importantly, each formulation induces unique long non-coding RNA (lncRNA) signatures, implicating lncRNAs in fibroblast-mediated skin remodeling. These findings highlight the novel design of PLLA microspheres as a critical determinant of their therapeutic outcome, offering a molecular basis for developing safer and more effective skin rejuvenation strategies.
皮肤老化的特征是成纤维细胞减少和细胞外基质（ECM）降解，这促使聚-L-乳酸（PLLA）真皮注射剂被广泛用于激活成纤维细胞、刺激新胶原生成和使皮肤年轻化。然而，目前的PLLA制剂疗效不一，可能引发不良炎症反应。在本研究中，我们比较了两种不同的PLLA制剂——一种含有新型微球形PLLA（PLLA-LASYNPRO），另一种含有微片状PLLA——以评估它们对人真皮成纤维细胞和皮肤组织的不同影响。结果表明，PLLA微球促进成纤维细胞迁移、ECM合成和伤口收缩，而PLLA微片抑制增殖并引发炎症基因表达。转录组分析显示，PLLA微球上调参与脂肪细胞分化和能量代谢的基因，免疫激活最小。相比之下，PLLA微片触发免疫途径并抑制再生信号。重要的是，每种制剂都诱导独特的长链非编码RNA（lncRNA）特征，表明lncRNAs参与成纤维细胞介导的皮肤重塑。这些发现突出了PLLA微球的新颖设计是其治疗效果的关键决定因素，为开发更安全、更有效的皮肤年轻化策略提供了分子基础。
