title: Adipogenic factor-loaded microspheres increase retention of transplanted adipose tissue.
abstract: The aim of this study was to develop and test a controlled delivery system of two adipogenic factors (insulin and dexamethasone [Dex]), to generate stable adipose tissue when mixed with disaggregated human fat. Both drugs were encapsulated in poly(lactic-co-glycolic acid), (PLGA) microspheres (MS) and mixed with human lipoaspirate to induce adipogenesis in vivo. It was hypothesized that the slow release of insulin and Dex would enhance both adipogenesis and angiogenesis, thus retaining the fat graft volume in a nude mouse model. Insulin/Dex-loaded PLGA MS (Insulin/Dex MS) were prepared using both single and double emulsion/solvent extraction techniques. The bioactivity of the drugs was assessed by mixing the MS with human lipoaspirate and injecting subcutaneously into the dorsal aspect of an athymic mouse. Five doses of the drugs were examined and samples were analyzed grossly and histologically after 5 weeks in vivo. Mass and volume of the grafts were measured with the microsphere-containing samples, demonstrating increased mass and volume with increasing drug doses. Histological analysis, including H&E and CD31, indicated increased vascularization within the insulin/Dex MS-containing samples compared with the lipoaspirate-only samples. This study demonstrates that the controlled delivery of adipogenic factors such as insulin and Dex through polymer MS can significantly enhance tissue formation and vascularization, therefore presenting a potentially clinically relevant model of adipose retention.
authors.affiliation: 1 Department of Plastic Surgery, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Arta
authors.initials: A
authors.lastname: Kelmendi-Doko
authors.forename: Kacey G
authors.initials: KG
authors.lastname: Marra
authors.forename: Natasa
authors.initials: N
authors.lastname: Vidic
authors.forename: Huaping
authors.initials: H
authors.lastname: Tan
authors.forename: J Peter
authors.initials: JP
authors.lastname: Rubin
mesh_terms: D050156:Adipogenesis / Q000187:drug effects / Q000502:physiology*; D000273:Adipose Tissue / Q000187:drug effects / Q000254:growth & development* / Q000637:transplantation*; D000818:Animals; D002214:Capsules / Q000008:administration & dosage / Q000737:chemistry; D003907:Dexamethasone / Q000008:administration & dosage* / Q000737:chemistry; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D015195:Drug Design; D005260:Female; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry; D008422:Materials Testing; D051379:Mice; D008819:Mice, Nude; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*
chemical_list: D002214:Capsules; D004338:Drug Combinations; D007328:Insulin; D003907:Dexamethasone