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We hypothesized that increasing the energy demand of adipose tissue is a promising strategy to combat excessive lipid accumulation. Resveratrol, a natural polyphenol, activates lipid catabolism in fat tissue; however, its clinical success is hindered by poor bioavailability. Here, we implanted resveratrol releasing poly(lactide\u2010co\u2010glycolide) scaffolds into epididymal fat to overcome its poor bioavailability with the goal of enhancing local lipid catabolism. In lean mice, resveratrol scaffolds decreased adipocyte size relative to scaffolds with no drug, a response that correlated with AMP kinase activation. Immunohistochemistry indicated that macrophages and multinucleated giant cells within the scaffold expressed carnitine palmitoyltransferase 1 (CPT1) at higher levels than other cells in the adipose tissue. Furthermore, resveratrol increased CPT1 levels in cultured macrophages. Taken together, we propose that resveratrol scaffolds decrease adipocyte size because resveratrol increases lipid utilization in scaffold\u2010infiltrating immune cells, possibly through elevating CPT1 levels or activity. In a follow\u2010up study, mice that received resveratrol scaffolds 28\u2010day prior to a high\u2010fat diet exhibited decreased weight gain, adipose tissue expansion, and adipocyte hypertrophy compared to mice with control scaffolds. Notably, this scaffold\u2010based strategy required a single resveratrol administration compared to the daily regiment generally needed for oral administration. These results indicate that localized delivery of metabolism modulating agents to the adipose tissue may overcome issues with bioavailability and that the role of biomaterials should be further investigated in this therapeutic strategy for metabolic disease.<\/jats:p>","DOI":"10.1002\/jbm.a.37063","type":"journal-article","created":{"date-parts":[[2020,7,18]],"date-time":"2020-07-18T13:39:31Z","timestamp":1595079571000},"page":"766-778","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Modulation of adipocyte size and fat pad weight via resveratrol releasing scaffolds implanted into the epididymal adipose tissue"],"prefix":"10.1002","volume":"109","author":[{"given":"Kendall P.","family":"Murphy","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering University of South Carolina  Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Hendley","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Program University of South Carolina  Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra T.","family":"Patterson","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering University of South Carolina  Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayley E.","family":"Hall","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Program University of South Carolina  Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Griffin J.","family":"Carter","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Program University of South Carolina  Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Isely","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering University of South Carolina  Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1622-977X","authenticated-orcid":false,"given":"R. 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