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Significance:An understanding of the physiology of wound healing and scarring is necessary to minimize surgical scar formation. By reducing tension across the healing wound, eliminating excess inflammation and infection, and encouraging perfusion to healing areas, surgeons can support healing and minimize scarring.Recent Advances:Preoperatively, newer techniques focused on incision placement to minimize tension, skin sterilization to minimize infection and inflammation, and control of comorbid factors to promote a healing process with minimal scarring are constantly evolving. Intraoperatively, measures like layered closure, undermining, and tissue expansion can be taken to relieve tension across the healing wound. Appropriate suture technique and selection should be considered, and finally, there are new surgical technologies available to reduce tension across the closure. Postoperatively, the healing process can be supported as proliferation and remodeling take place within the wound. A balance of moisture control, tension reduction, and infection prevention can be achieved with dressings, ointments, and silicone. Vitamins and corticosteroids can also affect the scarring process by modulating the cellular factors involved in healing.Critical Issues:Healing with no or minimal scarring is the ultimate goal of wound healing research. Understanding how mechanical tension, inflammation and infection, and perfusion and hypoxia impact profibrotic pathways allows for the development of therapies that can modulate cytokine response and the wound extracellular microenvironment to reduce fibrosis and scarring.Future Directions:New tension-off loading topical treatments, laser, and dermabrasion devices are under development, and small molecule therapeutics have demonstrated scarless wound healing in animal models, providing a promising new direction for future research aimed to minimize surgical scarring.

Objective:To design and validate a novel murine model of full-thickness (FT) vaginal wound healing that mirrors postinjury tissue repair and underscores the impact of estrogen signaling-driven healing kinetics, inflammation, and neovascularization.Approach:Five-week-old female CD1 mice were subjected to two 1-mm FT wounds. To assess wound healing kinetics, vaginas were harvested at 6, 12, 18, 24, 48, and 72 h and 7 days postinjury. Wounds from all time points were analyzed by hematoxylin and eosin and trichrome to, respectively, assess the rate of wound closure and tissue deposition. Inflammatory leukocyte (CD45), neutrophil (Ly6G), and macrophage (F480 and CD206) infiltration was examined by immunohistochemistry (IHC) and the resulting anti-inflammatory M2 (CD206)/total (F480) macrophage ratio quantified. Neovascularization (CD31) and estrogen receptor-α (ERα) expression levels were similarly determined by IHC.Results:We observed rapid healing with resolution of mucosal integrity by 48 h (p< 0.05), and overall neutrophils and polarized type 2 macrophages (M2) apexed at 12 h and reduced to near control levels by day 7 postinjury. Tissue repair was virtually indistinguishable from the surrounding vagina. CD31+vessels increased between 12 h and day 7 and ERα trended to decrease at 12 h postinjury and rebound at day 7 to uninjured levels.Innovation:A proof-of-concept murine model to study vaginal wound healing kinetics and postinjury regenerative repair in the vagina was developed and verified.Conclusion:We surmise that murine vaginal mucosal repair is accelerated and potentially regulated by estrogen signaling through the ERα, thus providing a cellular and molecular foundation to understand vaginal healing responses to injury.

Objective:Gastrostomy tubes (GTs) are one of the most common procedures in neonatal surgery, and their malfunction represents one of the most common complaints in the emergency room and clinic. Complications can occur in up to one-third of patients and include pain, peristomal leak, and infection, but can range in severity. We hypothesize that a preventative strategy employing a GT fixation dressing at the time of operation minimizes these postoperative complications in neonates.Approach:All patients less than 1 year of age who underwent laparoscopic GT placement by a single surgeon in the study period were reviewed. All tubes were secured in place on the external abdominal wall for 2 weeks postoperatively. Demographics and outcomes were evaluated.Results:Fifty-three percent of our cohort were male, and 47% were premature. The most common indication for placement was failure to thrive (59%), and common comorbid conditions were characterized as neurologic (71%), and cardiac (59%). The dressing did not prevent hypertrophic granulation tissue formation, but no patient experienced surgical site infection or device-related pressure injury at 30 and 120 days postoperatively. No patient required reoperation or readmission.Innovation:This simple, one-time, cost-effective fixation dressing has the potential to reduce some of the most common postoperative surgical issues in neonatal patients and can be applied in almost any health care setting.Conclusions:A dressing aimed at tube fixation and immobilization for the first two postoperative weeks averts some of the major complications of GT placement over a standard follow-up period as compared with the literature.

Objective:Our goal was to develop a chronic wound model in mice that avoids implantation of foreign material or impaired immunity and to use this to characterize the local and systemic immune response associated with Pseudomonas aeruginosainfection.Approach:We generated bilateral full-thickness dermal wounds in healthy 10–12-week-old C57Bl6 mice. We waited 24 h to inoculate the developing wound eschar at these sites. We performed careful titration experiments with luminescent strains of P. aeruginosato identify bacterial inoculation concentrations that consistently established stable infections in these animals. We performed flow cytometry-based immunophenotyping of immune cell infiltrates at the wound site, spleen, and draining lymph nodes over time. Finally, we compared inflammatory responses seen in wound inoculation with planktonic bacteria, preformed biofilm, and heat-killed (HK) P. aeruginosa.Results:Using this delayed inoculation model and 7.5 ± 2.5 × 102CFU/mL of PAO1 we consistently established stable infections that lasted at 10 days in duration. During early infection, we detected a strong upregulation of inflammatory cytokines and neutrophil infiltration at the wound site, while natural killer (NK) cells and dendritic cells (DCs) were reduced. At the systemic level, only plasmacytoid DCs were increased early in infection. During later stages, there was systemic upregulation of B cells, T cells, and macrophages, whereas NK cells and interferon killer DCs were reduced. Infections with P. aeruginosabiofilms were not more virulent than infections with planktonic P. aeruginosa, whereas treatment with HK P. aeruginosaonly induces a short-term inflammatory state.Innovation:We describe a versatile wound model of chronic P. aeruginosainfection that lasts 10 days without causing sepsis or other excessive morbidity.Conclusion:This model may facilitate the study of chronic wound infections in immunocompetent mice. Our findings also highlight the induction of early innate immune cell populations during P. aeruginosainfection.

Significance:Fetal wounds heal with a regenerative phenotype that is indistinguishable from surrounding skin with restored skin integrity. Compared to this benchmark, all postnatal wound healing is impaired and characterized by scar formation. The biologic basis of the fetal regenerative phenotype can serve as a roadmap to recapitulating regenerative repair in adult wounds. Reduced leukocyte infiltration, likely mediated, in part, through changes in the chemokine milieu, is a fundamental feature of fetal wound healing.Recent Advances:The contributions of chemokines to wound healing are a topic of active investigation. Recent discoveries have opened the possibility of targeting chemokines therapeutically to treat disease processes and improve healing capability, including the possibility of achieving a scarless phenotype in postnatal wounds.Critical Issues:Successful wound healing is a complex process, in which there is a significant interplay between multiple cell types, signaling molecules, growth factors, and extracellular matrix. Chemokines play a crucial role in this interplay and have been shown to have different effects in various stages of the healing process. Understanding how these chemokines are locally produced and regulated during wound healing and how the chemokine milieu differs in fetal versus postnatal wounds may help us identify ways in which we can target chemokine pathways.Future Directions:Further studies on the role of chemokines and their role in the healing process will greatly advance the potential for using these molecules as therapeutic targets.

Background:Mesenchymal stem cells (MSCs) are key to regenerative wound healing. MSCs have spatial memory and respond to local environment. MSCs orchestrate wound repair by: (1) structural repair via cellular differentiation; (2) immune-modulation; (3) secretion of growth factors that drive neovascularization and re-epithelialization; and (4) mobilization of resident stem cells.The Problem:Autologous bone-marrow-derived cells and MSCs demonstrate improved healing and tissue-integrity in animal models and clinical trials. However, the effects are variable and the mechanisms of MSC-mediated wound healing are not fully understood. The mammalian MSC niche and signaling sequences and factors affecting their homing, differentiation, viability, and safety need to be characterized to get full benefits of MSC cellular therapy.Basic/Clinical Science Advances:MSCs can be isolated from bone-marrow, and less-invasive tissues such as adipose, gingiva, muscle, and umbilical cord, with similar functional effects. However, isolation, culture conditions, and markers used to identify and trace the lineage of these MSCs have not been standardized, which is crucial to determine the extent to which MSCs act as multipotent stem cells or sources of secreted factors in wounds.Clinical Care Relevance:In chronic nonhealing wounds, where efficacy of conventional therapies is unsatisfactory, autotransplantation of MSCs could accelerate wound healing, promote regeneration and restoration of tissue integrity, and reduce recurrence of wounds at characteristically predisposed sites.Conclusion:Regenerative medicine and novel wound therapies using autologous stem cells holds great promise for clinical management of difficult wounds. The ideal candidate stem cells can be used to repopulate the wound bed to mediate appropriate epidermal and dermal regeneration and promote efficient wound repair, while modulating the immune system to prevent infection.