In the skin, tissue injury results in fibrosis in the form of scars composed of dense extracellular matrix deposited by fibroblasts. The therapeutic goal of regenerative wound healing has remained elusive, in part because principles of fibroblast programming and adaptive response to injury remain incompletely understood. Here, we present a multimodal -omics platform for the comprehensive study of cell populations in complex tissue, which has allowed us to characterize the cells involved in wound healing across both time and space. We employ a stented wound model that recapitulates human tissue repair kinetics and multiple Rainbow transgenic lines to precisely track fibroblast fate during the physiologic response to skin injury. Through integrated analysis of single cell chromatin landscapes and gene expression states, coupled with spatial transcriptomic profiling, we are able to impute fibroblast epigenomes with temporospatial resolution. This has allowed us to reveal potential mechanisms controlling fibroblast fate during migration, proliferation, and differentiation following skin injury, and thereby reexamine the canonical phases of wound healing. These findings have broad implications for the study of tissue repair in complex organ systems.
Background: The optimal time for flap anastomosis to an arteriovenous loop remains controversial. Whether perforator flaps and axially vascularized muscle or fasciocutaneous flaps lead to comparable outcomes in conjunction with arteriovenous loops has not been investigated. Methods: Medical records from 103 patients undergoing arteriovenous loop reconstruction (76 one-stage and 27 two-stage) between 2007 and 2017 were reviewed. Postoperative outcomes were compared between one- and two-stage arteriovenous loop reconstructions and different types of free flaps. Results: Rates of flap thrombosis, major wound complications, and flap failure did not differ significantly between one- and two-stage arteriovenous loop reconstructions (14.47 percent versus 11.11 percent, p = 1.00; 30.26 percent versus 25.93 percent, p = 0.67; and 10.53 percent versus 7.41 percent, p = 1.00). For two-stage arteriovenous loop reconstructions, the time interval between arteriovenous loop placement and flap anastomosis was a predictor for thrombotic events (OR, 1.31; p < 0.05). Anterolateral thigh flaps in conjunction with arteriovenous loops showed higher failure rates (33.33 percent) compared with all other flaps (6.59 percent) (p < 0.05) and combined latissimus dorsi and parascapular flaps (0 percent) (p < 0.05). Thrombosis rates were higher in anterolateral thigh flaps (33.33 percent) compared with all other flaps (10.99 percent; p = 0.056), and combined latissimus dorsi and parascapular flaps (0 percent; p < 0.05). Conclusions: Two-stage arteriovenous loop reconstructions do not lead to increased postoperative complications compared to one-stage arteriovenous loop reconstructions and may be favorable in complicated cases because of shorter operative times. To avoid an increased thrombosis risk, flap anastomosis should not be delayed beyond 10 days in two-stage arteriovenous loop reconstructions. Anterolateral thigh flaps are less suitable for arteriovenous loop reconstructions because of higher complication rates. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.
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