Controlled delivery system for adipose tissue retention

Abstract

Current materials used for adipose tissue reconstruction have critical shortcomings such as suboptimal volume retention, donor site morbidity, and poor biocompatibility. The aim of this study was to develop and examine a controlled delivery system of dexamethasone (Dex) to generate stable adipose tissue when mixed with disaggregated human fat in an athymic mouse model for up to six months. The hypotheses that the slow release of Dex from polymeric microspheres would enhance both adipogenesis and angiogenesis, resulting in long term adipose volume retention, was tested using two microsphere drug delivery systems. In one treatment group, Dex was encapsulated within single-walled poly(lactic-co-glycolic acid) (PLGA) microspheres (Dex SW MS), and in the second, Dex was encapsulated in a (PLGA) core surrounded by a shell of poly(L-lactic acid) (PLLA). The double-walled polymer microsphere system was developed to create a slower and more sustainable drug delivery process. The Dex loaded microspheres were then mixed with human lipoaspirate. Both single- and double-walled empty microspheres and lipoaspirate-only controls were examined. A treatment group consisted of 3 different combinations of microspheres including a group of single- and double-walled CONTROLLED DELIVERY SYSTEM FOR ADIPOSE TISSUE RETENTION Arta Kelmendi-Doko, MD, PhD University of Pittsburgh, 2016 v empty microspheres combined and lipoaspirate only as a control was also examined in the nude mouse model. Samples were analyzed grossly and histologically after 6 weeks and 6 months in vivo. Mass and volume were measured; Dex microsphere-containing, dose of 27 mg double-walled microspheres samples demonstrated greater adipose tissue retention (80±12%) compared to the control group (10±7.3%) at 6 months time point. Histological analysis, including H&E and CD31 staining, indicated increased vascularization (p<0.05) within the Dex MS-containing samples. Adipose tissue injected in animals was affected by dexamethasone-loaded microspheres showing an improvement in mass and volume measurements. Histology of the extracted fat shows overall healthy adipose tissue morphology with the great presence of vascularity in the treatment groups. Controlled delivery of adipogenic factors, such as dexamethasone via polymer microspheres, significantly affects adipose tissue retention by maintaining healthy tissue formation and vascularization. The use of microspheres as a vehicle for controlled drug delivery of adipogenic factors therefore presents a clinically relevant model of adipose retention