Faster Efficacy and Reduced Nodule Occurrence with Porous PLLA (Poly-L-Lactic Acid) Porous Microspheres

Qihua Cao^1,2,3,4Jiayu Chen^2,4,5,6Zijun Zhang⁶Yufei Xiong⁵Jinxia Ma⁵Wei Sun⁵Xin Chen⁵Qilei Lou⁵TANG Kaijia^2,3,4,5Feng Lin^2,3,4*Yueliang Zhu^2,3,4*Xiaohua Yu^1,2,3,4,5*

• ¹Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
• ²Orthopedics Research Institute of Zhejiang University, Hangzhou City, China
• ³Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, China
• ⁴Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou City, China
• ⁵Hangzhou Philosopher’s Stone Biotechnology Co., Ltd, Hangzhou City, China
• ⁶Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China

Poly-L-lactic acid (PLLA) has gained prominence as an injectable dermal filler as it can both stimulate collagen regeneration and deliver long-lasting effects.However, its application is often hampered by delayed therapeutic onset and adverse events, particularly nodule formation., likely due to uneven distribution caused by the easy formation of small clumps during PLLA reconstitution.Addressing these limitations, this study explores the use of NH4HCO3 as a porogen to fabricate porous microspheres with a honeycomb-like internal structure through a double emulsion solvent evaporation technique. These medium porosity microspheres exhibit a porous exterior that increases surface-to-volume ratio, facilitating cellular adherence and faster biodegradation. In vivo experiments demonstrated that these porous microspheres facilitate greater inflammatory cell infiltration and more rapid, substantial collagen production compared to solid microspheres. Additionally, their porous configuration reduces density, allowing for extended suspension and uniform distribution that minimizes micro-aggregate formation and subsequent nodule development. The reduced injection force also enhances clinical applicability.Overall, porous PLLA microspheres represent a potential improvement in dermal filler technology by expediting tissue regeneration and reducing complications associated with nodule formation.