D-α-tocopherol acetate and hydroxyapatite composite poly(D,L-lactic acid) microspheres suppress sterile inflammation by improving microenvironment

Improve the sterile inflammation caused by soft tissue fillers. • Reduce inflammatory mediators and ROS levels. • Promoted cell migration and orderly collagen deposition. The increasing prevalence of soft tissue fillers has given rise to a concern regarding the occurrence of local sterile inflammation induced by the filler material. This study proposes the use of Poly(D,L-lactic acid) (PDLLA) microspheres composite with D-α-Tocopherol acetate (α-TA) and Hydroxyapatite (HAp) to eliminate aseptic inflammation caused by PDLLA degradation. The reduction of aseptic inflammation is achieved by prolonging degradation time, modulating the local microenvironment, and suppressing inflammatory mediators. HAp and α-TA were evenly distributed in PDLLA/HAp(α-TA) microspheres, and those microspheres have a particle size suitable for soft tissue filling (30–70 µm). Utilizing a conventional commercial formulation, PDLLA/HAp(α-TA) is uniformly amalgamated with carboxymethyl cellulose (CMC) to formulate CMC@PDLLA/HAp(α-TA) gel. CMC@PDLLA/HAp(α-TA) exhibits sustained release properties for at least 6 weeks and possesses excellent injectability. Meanwhile, CMC@PDLLA/HAp(α-TA) exhibits excellent biocompatibility and the ability to promote cell migration. Specifically, CMC@PDLLA/HAp(α-TA) significantly reduces inflammatory mediators and reactive ROS levels, while exhibiting prolonged and orderly collagen deposition. In summary, as an injectable soft tissue filler, CMC@PDLLA/HAp(α-TA) offers a novel strategy for the long-term suppression of sterile inflammation. Download: Download high-res image (287KB) Download: Download full-size image