Search

Hair follicle neogenesis (HFN) occurs after large skin excisions in mice, serving as a rare regenerative model in mammalian wound healing. Wound healing typically results in fibrosis in mice and humans. We previously showed that small skin excisions in mice result in scarring devoid of HFN, displaying features of nonregenerative healing, and hedgehog (Hh) activation in the dermis of such wounds can induce HFN. In this study, we sought to verify the role of dermal Wnt/β-catenin signaling in HFN because this pathway is essential for hair follicle development but is also paradoxically well-characterized in fibrosis of adult wounds. By deletion of β-catenin in large wound myofibroblasts, we show that Wnt/β-catenin signaling is required for endogenous mechanisms of HFN. By utilizing a combined mouse model that simultaneously induces deletion of β-catenin and constitutive activation of Smoothened in myofibroblasts, we also found that β-catenin is required for Hh-driven dermal papilla formation. Transcriptome analysis confirms that Wnt/β-catenin and Hh pathways are activated in dermal papilla cells. Our results indicate that Wnt-active fibrotic status may also create a permissive state for the regenerative function of Hh, suggesting that activation of both Wnt and Hh pathways in skin wound fibroblasts must be ensured in future strategies to promote HFN., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: A deeper understanding of acute rejection in vascularized composite allotransplantation is paramount for expanding its utility and longevity. There remains a need to develop more precise and accurate tools for diagnosis and prognosis of these allografts, as well as alternatives to traditional immunosuppressive regimens., Methods: Twenty-seven skin biopsies collected from 3 vascularized composite allotransplantation recipients, consisting of face and hand transplants, were evaluated by histology, immunohistochemistry staining, and gene expression profiling., Results: Biopsies with clinical signs and symptoms of rejection, irrespective of histopathological grading, were significantly enriched for genes contributing to the adaptive immune response, innate immune response, and lymphocyte activation. Inflammation episodes exhibited significant fold change correlations between the face and hands, as well as across patients. Immune checkpoint genes were upregulated during periods of inflammation that necessitated treatment. A gene signature consisting of CCL5 , CD8A , KLRK1 , and IFNγ significantly predicted inflammation specific to vascularized composite allografts that required therapeutic intervention., Conclusions: The mechanism of vascularized composite allograft-specific inflammation and rejection appears to be conserved across different patients and skin on different anatomical sites. A concise gene signature can be utilized to ascertain graft status along with a continuous scale, providing valuable diagnostic and prognostic information to supplement current gold standards of graft evaluation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Objective: Rejection is common and pernicious following Vascularized Composite Allotransplantation (VCA). Current monitoring and diagnostic modalities include the clinical exam which is subjective and biopsy with dermatohistopathologic Banff grading, which is subjective and invasive. We reviewed literature exploring non- and minimally invasive modalities for diagnosing and monitoring rejection (NIMMs) in VCA., Methods: PubMed, Cochrane, and Embase databases were queried, 3125 unique articles were reviewed, yielding 26 included studies exploring 17 distinct NIMMs. Broadly, NIMMs involved Imaging, Liquid Biomarkers, Epidermal Sampling, Clinical Grading Scales, and Introduction of Additional Donor Tissue., Results: Serum biomarkers including MMP3 and donor-derived microparticles rose with rejection onset. Epidermal sampling non-invasively enabled measurement of cytokine & gene expression profiles implicated in rejection. Both hold promise for monitoring. Clinical grading scales were useful diagnostically as was reflection confocal microscopy. Introducing additional donor tissue showed promise for preemptively identifying rejection but requires additional allograft tissue burden for the recipient., Conclusion: NIMMs have the potential to dramatically improve monitoring and diagnosis in VCA. Many modalities show promise however, additional research is needed and a multimodal algorithmic approach should be explored., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

The current standard of care for an alveolar cleft defect is an autogenous bone graft, typically from the iliac crest. Given the limitations of alveolar bone graft surgery, such as limited supply, donor site morbidity, graft failure, and need for secondary surgery, there has been growing interest in regenerative medicine strategies to supplement and replace traditional alveolar bone grafts. Though there have been preliminary clinical studies investigating bone tissue engineering methods in human subjects, lack of consistent results as well as limitations in study design make it difficult to determine the efficacy of these interventions. As the field of bone tissue engineering is rapidly advancing, reconstructive surgeons should be aware of the preclinical studies informing these regenerative strategies. We review preclinical studies investigating bone tissue engineering strategies in large animal maxillary or mandibular defects and provide an overview of scaffolds, stem cells, and osteogenic agents applicable to tissue engineering of the alveolar cleft. An electronic search conducted in the PubMed database up to December 2021 resulted in 35 studies for inclusion in our review. Most studies showed increased bone growth with a tissue engineering construct compared to negative control. However, heterogeneity in the length of follow up, method of bone growth analysis, and inconsistent use of positive control groups make comparisons across studies difficult. Future studies should incorporate a pediatric study model specific to alveolar cleft with long-term follow up to fully characterize volumetric defect filling, cellular ingrowth, bone strength, tooth movement, and implant support., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Early surgical exposure and research fellowships can influence medical students' specialty choice, increase academic productivity, and impact residency match. However, to our knowledge, there is no published guidance on the programmatic evaluation and quality enhancement necessary for the sustainability of formal plastic surgery summer research programs for first year medical students. We present seven years (2013-2020) of institutional experience in an effort to inform program development at other institutions., Methods: From 2013 to 2016, a sole basic science research arm existed. In 2017, a clinical research arm was introduced, with several supplemental activities, including surgical skills curriculum. A formalized selection process was instituted in 2014. Participant feedback was analyzed annually. Long-term outcomes included continued research commitment, productivity, and residency match., Results: The applicant pool reached 96 applicants in 2019, with 85% from outside institutions. Acceptance rate reached 7% in 2020. With adherence to a scoring rubric for applicant evaluation, good to excellent interrater reliability was achieved (intraclass correlation coefficient = 0.75). Long-term outcomes showed that on average per year, 28% of participants continued involvement in departmental research and 29% returned for dedicated research. Upon finishing medical school, participants had a mean of 7 ± 4 peer-reviewed publications. In total, 62% of participants matched into a surgical residency program, with 54% in integrated plastic surgery., Conclusions: A research program designed for first year medical students interested in plastic surgery can achieve academic goals. Students are provided with mentorship, networking opportunities, and tools for self-guided learning and career development., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Significance: Skin wounds and disorders compromise the protective functions of skin and patient quality of life. Although accessible on the surface, they are challenging to address due to paucity of effective therapies. Exogenous extracellular vesicles (EVs) and cell-free derivatives of adult multipotent stromal cells (MSCs) are developing as a treatment modality. Knowledge of origin MSCs, EV processing, and mode of action is necessary for directed use of EVs in preclinical studies and methodical translation. Recent Advances: Nanoscale to microscale EVs, although from nonskin cells, induce functional responses in cutaneous wound cellular milieu. EVs allow a shift from cell-based to cell-free/derived modalities by carrying the MSC beneficial factors but eliminating risks associated with MSC transplantation. EVs have demonstrated striking efficacy in resolution of preclinical wound models, specifically within the complexity of skin structure and wound pathology. Critical Issues: To facilitate comparison across studies, tissue sources and processing of MSCs, culture conditions, isolation and preparations of EVs, and vesicle sizes require standardization as these criteria influence EV types and contents, and potentially determine the induced biological responses. Procedural parameters for all steps preceding the actual therapeutic administration may be the key to generating EVs that demonstrate consistent efficacy through known mechanisms. We provide a comprehensive review of such parameters and the subsequent tissue, cellular and molecular impact of the derived EVs in different skin wounds/disorders. Future Directions: We will gain more complete knowledge of EV-induced effects in skin, and specificity for different wounds/conditions. The safety and efficacy of current preclinical xenogenic applications will favor translation into allogenic clinical applications of EVs as a biologic.