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Burns and other traumatic injuries represent a substantial biomedical burden. The current standard of care for deep injuries is autologous split-thickness skin grafting (STSG), which frequently results in contractures, abnormal pigmentation, and loss of biomechanical function. Currently, there are no effective therapies that can prevent fibrosis and contracture after STSG. Here, we have developed a clinically relevant porcine model of STSG and comprehensively characterized porcine cell populations involved in healing with single-cell resolution. We identified an up-regulation of proinflammatory and mechanotransduction signaling pathways in standard STSGs. Blocking mechanotransduction with a small-molecule focal adhesion kinase (FAK) inhibitor promoted healing, reduced contracture, mitigated scar formation, restored collagen architecture, and ultimately improved graft biomechanical properties. Acute mechanotransduction blockade up-regulated myeloid CXCL10-mediated anti-inflammation with decreased CXCL14-mediated myeloid and fibroblast recruitment. At later time points, mechanical signaling shifted fibroblasts toward profibrotic differentiation fates, and disruption of mechanotransduction modulated mesenchymal fibroblast differentiation states to block those responses, instead driving fibroblasts toward proregenerative, adipogenic states similar to unwounded skin. We then confirmed these two diverging fibroblast transcriptional trajectories in human skin, human scar, and a three-dimensional organotypic model of human skin. Together, pharmacological blockade of mechanotransduction markedly improved large animal healing after STSG by promoting both early, anti-inflammatory and late, regenerative transcriptional programs, resulting in healed tissue similar to unwounded skin. FAK inhibition could therefore supplement the current standard of care for traumatic and burn injuries.

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Background: Bleeding is a negative outcome predictor in liver surgery. Reduction in the abdominal wall trauma in major hepatectomy is challenging but might offer possible benefits for the patient. This study was conducted to assess hemostasis techniques in single-port major hepatectomies (SP-MajH) as compared to multiport major hepatectomies (MP-MajH). Methods: The non-randomized study comprised 34 SP-MajH in selected patients; 14 MP-MajH served as the control group. Intraoperative blood loss and number of blood units transfused served as the primary endpoints. Secondary endpoints were complications and oncologic five-year outcome. Results: All resections were completed without converting to open surgery. Time for hepatectomy did not differ between SP-MajH and MP-MajH. Blood loss and number of patients with blood loss > 25 mL were significantly larger in MP-MajH (p = 0.001). In contrast, bleeding control was more difficult in SP-MajH, resulting in more transfusions (p = 0.008). One intestinal laceration (SP-MajH) accounted for the only intraoperative complication; 90-day mortality was zero. Postoperative complications were noted in total in 20.6% and 21.4% of patients for SP-MajH and MP-MajH, respectively. No incisional hernia occurred. During a median oncologic follow-up at 61 and 56 months (SP-MajH and MP-MajH), no local tumor recurrence was observed. Conclusions: SP-MajH requires sophisticated techniques to ensure operative safety. Substantial blood loss requiring transfusion is more likely to occur in SP-MajH than in MP-MajH.