90. Tendon Recovery with Adipose-derived Stem Cells: A Novel Model

Abstract

BACKGROUND:There is a delicate balance between physiologic healing and formation of unfavorable scars. Homeostasis between extracellular matrix (ECM) deposition and remodeling is maintained by an array of interconnected signaling networks with situationally-dependent functions. We previously demonstrated that systemic mineralocorticoid receptor (MR) inhibition improves epithelialization and diminishes collagen deposition without eroding scar strength. MR-inhibition, however, has a range of offtarget effects when applied systemically. Consequently, herein we evaluated the role of local MR-inhibition in wound healing and hypothesize that signaling through the MR on macrophages contributes to a pro-fibrotic phenotype in wound healing.METHODS: Female C57Bl/6 mice sustained bilateral 6 mm full-thickness biopsies with stenting and were stratified into either a) vehicle control, b) 5% topical spironolactone, or c) systemic spironolactone. Systemic spironolactone was delivered intraperitoneally every three days, and topical cream formulations of spironolactone and vehicle control were reapplied every three days. Tegaderm was placed over the mice to allow topical cream to remain over wound. Mice were followed photographically for 6 weeks for time to re-epithelialization and terminal scar area. Wound biopsies were collected for gross architectural analysis and assess collagen, fibrin, and elastic fibers with Movat's pentachrome. RESULTS:By day 5, both spironolactone groups demonstrated epithelization with minimal contracture. Scar area was noted to be diminished in both the spironolactone