The iron chelator, deferoxamine (DFO), has been shown to potentially improve dermal radiation‐induced fibrosis (RIF) in mice through increased angiogenesis and reduced oxidative damage. This preclinical study evaluated the efficacy of two DFO administration modalities, transdermal delivery and direct injection, as well as temporal treatment strategies in relation to radiation therapy to address collateral soft tissue fibrosis. The dorsum of CD‐1 nude mice received 30 Gy radiation, and DFO (3 mg) was administered daily via patch or injection. Treatment regimens were prophylactic, during acute recovery, post‐recovery, or continuously throughout the experiment (n = 5 per condition). Measures included ROS‐detection, histology, biomechanics and vascularity changes. Compared with irradiated control skin, DFO treatment decreased oxidative damage, dermal thickness and collagen content, and increased skin elasticity and vascularity. Metrics of improvement in irradiated skin were most pronounced with continuous transdermal delivery of DFO. In summary, DFO administration reduces dermal fibrosis induced by radiation. Although both treatment modalities were efficacious, the transdermal delivery showed greater effect than injection for each temporal treatment strategy. Interestingly, the continuous patch group was more similar to normal skin than to irradiated control skin by most measures, highlighting a promising approach to address detrimental collateral soft tissue injury following radiation therapy.

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While past studies have suggested that plasticity exists between dermal fibroblasts and adipocytes, it remains unknown whether fat actively contributes to fibrosis in scarring. We show that adipocytes convert to scar-forming fibroblasts in response to Piezo-mediated mechanosensing to drive wound fibrosis. We establish that mechanics alone are sufficient to drive adipocyte-to-fibroblast conversion. By leveraging clonal-lineage-tracing in combination with scRNA-seq, Visium, and CODEX, we define a mechanically naive fibroblast-subpopulation that represents a transcriptionally intermediate state between adipocytes and scar-fibroblasts. Finally, we show that Piezo1 or Piezo2-inhibition yields regenerative healing by preventing adipocytes activation to fibroblasts, in both mouse-wounds and a novel human-xenograft-wound model. Importantly, Piezo1-inhibition induced wound regeneration even in pre-existing established scars, a finding that suggests a role for adipocyte-to-fibroblast transition in wound remodeling, the least-understood phase of wound healing. Adipocyte-to-fibroblast transition may thus represent a therapeutic target for minimizing fibrosis via Piezo-inhibition in organs where fat contributes to fibrosis.

Objective: Mandibular distraction osteogenesis (MDO) is frequently performed to address airway obstruction in patients with Pierre Robin sequence (PRS), though more recently the technique of orthodontic airway plating (OAP) has gained traction. We aimed to evaluate OAP compared to MDO for airway obstruction in PRS. Design: A systematic literature search across PubMed, Embase, and Google Scholar identified all studies published in English, which involved MDO or any form of OAP as treatments for PRS. All relevant articles were reviewed in detail and reported on, adhering to PRISMA guidelines. Main Outcome Measures: Airway (tracheostomy avoidance, decannulation rate), feeding (full oral feeding tolerance). Results: Literature search identified 970 articles, of which 42 MDO studies and 9 OAP studies met criteria for review. A total of 1159 individuals were treated with MDO, and 322 individuals were treated with OAP. Primary outcomes appear similar for MDO and OAP at face value; however, this must be interpreted with different pretreatment contexts in mind. Conclusions: Orthodontic airway plating may be considered for airway obstruction in PRS, as some airway-related and feeding-related outcomes appear similar with MDO, per existing evidence in the literature. However, since PRS severity differed between studies, OAP cannot be uniformly considered a replacement for MDO. Further research is required to more comprehensively assess these treatment modalities inclusive of metrics that allow for direct comparison.