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Wound healing is a continuous and complex process regulated by multiple factors, which has become an intractable clinical burden. Mesenchymal stem cell-derived exosomes (MSC-exos) possess low immunogenicity, easy preservation, and potent bioactivity, which is a mirror to their parental cells MSC-exos are important tools for regulating the biological behaviors of wound healing-associated cells, including fibroblasts, keratinocytes, immune cells, and endothelial cells. MSC-exos accelerate the wound healing process at cellular and animal levels by modulating inflammatory responses, promoting collagen deposition and vascularization. MSC-exos accelerate wound healing at the cellular and animal levels by modulating inflammatory responses and promoting collagen deposition and vascularization. This review summarizes the roles and mechanisms of MSC-exos originating from various sources in promoting the healing efficacy of general wounds, diabetic wounds, burn wounds, and healing-related scars. It also discusses the limitations and perspectives of MSC-exos in wound healing, in terms of exosome acquisition, mechanistic complexity, and exosome potentiation modalities. A deeper understanding of the properties and functions of MSC-exos is beneficial to advance the therapeutic approaches for achieving optimal wound healing., Competing Interests: Declaration of competing interest All the authors declare that there is no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The apical extracellular matrix (aECM) of external epithelia often contains lipid-rich outer layers that contribute to permeability barrier function. The external aECM of nematodes is known as the cuticle and contains an external lipid-rich layer - the epicuticle. Epicuticlins are a family of tandem repeat cuticle proteins of unknown function. Here, we analyze the localization and function of the three C. elegans epicuticlins (EPIC proteins). EPIC-1 and EPIC-2 localize to the surface of the cuticle near the outer lipid layer, as well as to interfacial cuticles and adult-specific struts. EPIC-3 is expressed in dauer larvae and localizes to interfacial aECM in the buccal cavity. Skin wounding in the adult induces epic-3 expression, and EPIC proteins localize to wound sites. Null mutants lacking EPIC proteins are viable with reduced permeability barrier function and normal epicuticle lipid mobility. Loss of function in EPIC genes modifies the skin blistering phenotypes of Bli mutants and reduces survival after skin wounding. Our results suggest EPIC proteins define specific cortical compartments of the aECM and promote wound repair., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Introduction: Detection of critical colonization is gaining importance in wound management, but its pathophysiology remains unclear. We previously clarified that a dysbiotic wound microbiota differing from skin commensal microbiota may be involved in critical colonization and that such wounds contain fewer Forkhead box protein P3 (FOXP3)-positive cells in the tissue. However, it is not clear whether FOXP3-positive cells contribute to the development of critical colonization. Here, we examined whether inhibition of FOXP3-positive cell could induce critical colonization when the commensal microbiota was present in the wounds., Methods: Sprague-Dawley rats were administered FK506 or vehicle to inhibit differentiation into FOXP3-positive cells. Full-thickness wounds were made on the dorsal skin and inoculated with bacterial solution (dysbiosis group) or Luria-Bertani medium (commensal group). A bacterial solution was prepared by anaerobically culturing bacteria from the skin of donor rats on an artificial dermis in Luria-Bertani medium for 72 hours. Tissues were collected on day 4 postwounding for histological evaluation., Results: After microbiota transplantation, excessive inflammation occurred in the FK506 + commensal group. In contrast, wounds with transplanted dysbiotic microbiota showed the same level of neutrophil infiltration, regardless of FK506 administration. Furthermore, the wound area was larger in the FK506 + commensal group than in the vehicle + commensal group on day 4 postwounding ( P = 0.01). This area was also significantly larger in both the vehicle + dysbiosis ( P = 0.01) and FK506 + dysbiosis groups ( P = 0.03) than in the vehicle + commensal group., Conclusions: This study has shown that dysbiosis may be at least related to developing critical colonization, and the results suggest that FOXP3-positive cells are involved in this process. Our study may contribute to establishing new interventions that prevent critical colonization by correcting wound microbiota., Competing Interests: Conflicts of interest and sources of funding: T.M. and S.K. are members of the Department of Skincare Science, which receives financial support from Saraya Co, Ltd., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The healing of gastrointestinal anastomoses is a complex biological process influenced by numerous factors. Various strategies to support healing and prevent anastomotic leakage (AL) exist, encompassing preoperative, intraoperative and postoperative measures. Preoperative interventions aim to optimize the patient and the tissue environment, particularly the gut microbiome. Intraoperative measures are technical in nature and include the choice of surgical access, the anastomotic technique and anastomotic reinforcement. Various procedures of the intraoperative diagnostics enable identification of such anastomoses requiring additional protective measures. Recently, indocyanine green (ICG) fluoroscopy has become established for evaluation of tissue perfusion, while newer techniques such as spectral microscopy offer promising possibilities. Postoperative diagnostic methods aim to identify potential AL as early as possible to enable initiation of therapeutic steps even before the onset of symptoms. These procedures range from various imaging techniques to innovative bioresorbable, pH-sensitive implants for early AL detection. Due to the multifactorial genesis of AL and the diverse technical possibilities, no single method will become established for prevention of AL. Instead, a combination of measures will ultimately lead to optimal anastomotic healing. The use of artificial intelligence and analyses based on the data promises a better interpretation of the vast amount of data and therefore to be able to provide general recommendations., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Tissue regeneration is a complex process that involves the recruitment of various types of cells for healing after injury; it is mediated by numerous precise interactions. However, the identification of effective targets for improving tissue regeneration remains a challenge. As an extracellular matrix protein, Agrin plays a critical role in neuromuscular junction formation. Furthermore, recent studies have revealed the role of Agrin in regulating tissue proliferation and regeneration, which contributes to the repair process of injured tissues. An in‑depth understanding of the role of Agrin will therefore be of value. Given that repair and regeneration processes occur in various parts of the human body, the present systematic review focuses on the role of Agrin in typical tissue and highlights the potential signaling pathways that are involved in Agrin‑induced repair and regeneration. This review offers important insight into novel strategies for the future clinical applications of Agrin‑based therapies, which may represent a feasible treatment option for patients who require organ replacement or repair.

Assessment of wounds based on visual appearance has poor inter- and intra-rater reliability and it is difficult to differentiate between inflammation and infection. Thermography is a user-friendly quantitative image technique that collects the skin surface temperature pattern of the wound area and immediately visualizes the temperatures as a rainbow coloured diagram. The aim of this scoping review is to map and summarize the existing evidence on how thermography has been used to assess signs of inflammation in humans and animals with surgical or traumatic wounds. The method follows the Joanna Briggs Institute methodology. The databases searched were PubMed, Embase, CINAHL and Cochrane Library. 3798 sources were identified, 2666 were screened on title and abstract, 99 on full text and 19 studies were included for review. We found that the literature is diverse and originates from a variety of scientific fields. Thermography has been used to detect and predict inflammation and infection in surgical wounds. Grading systems based on the visual appearance correlate to temperature patterns detected with thermography. The general tendency is that thermography detects the temperature in a wound with inflammation to be warmer than a reference area or the same skin area before surgery. In a surgical wound the temperature is elevated 1-2 weeks after surgery due to natural physiological inflammation that induces healing, after 2 weeks the temperature of the wound area slowly and steady decreases to baseline over 1-3 months. If a secondary temperature peak happens during the healing phase of a surgical wound, it is likely that infection has occurred. Modern handheld thermographic cameras might be a promising tool for the clinician to quickly quantify the temperature pattern of surgical wounds to distinguish between inflammation and infection. However, firm evidence supporting infection thermography surveillance of surgical wounds as a technique is missing., Competing Interests: Declaration of competing interest The Authors declares that there is no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose of Review: Although the mucosal barrier serves as a primary interface between the environment and host, little is known about the repair of acute, superficial lesions or deeper, persistent lesions that if not healed, can be the site of increased permeability to luminal antigens, inflammation, and/or neoplasia development., Recent Findings: Studies on acute superficial lesions have been sparse in the past year, with more focus given to novel mechanisms of mucosal protection, and the way in which mature epithelial cells or committed stem cells dedifferentiate, reprogram, proliferate, and then regenerate the gastroduodenal mucosa after injury. For this, adenoviral therapy showed organ specific targeting with mRNA and protein expression of effectors to protect against mucosal injury and ulceration. A large database of plant-based agents known to protect against injury and ulceration was published, along with studies using plant-based compounds delivered with alginates, polysaccharide/gel floating rafts, or incorporated into nanoparticles or green carbon dots to improve targeting and retention at the ulcerated lesion. With RNA technology developing rapidly, particularly single-cell RNA sequencing, important and novel data was forthcoming on mucosal regeneration. In particular, the role of interleukin-17 hub proteins in mucosal healing was highlighted. The presence and role of injury reserve cells was determined, as was the composition of ligand gradients for cell differentiation in both stomach and duodenum. The role of amphiregulin in parietal cell differentiation from lineage-restricted stem cells and the Yap1 gene signature in metaplasia vs. healing ulcers were of particular importance. Additionally, studies unveiled the important role of mesenchymal stromal cells in differentiation and repair mechanisms, in Muse cells as an exciting new therapy for mucosal repair after injury, and the role of sympathetic neurons in activating the immune system to regulate mucosal repair mechanisms., Summary: Recent studies highlight novel mechanisms that promote mucosal regeneration after injury of the gastroduodenal mucosa., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To use three-dimensional anorectal ultrasonography (3D-US) to evaluate the outcome of ligation of the intersphincteric fistula tract (LIFT) in patients with crypto-glandular transsphincteric fistula and describing the patterns of healing, failure, and recurrence rate., Methods: After classifying the fistula and determining the length of the sphincter muscle to be transected, the patients were submitted to LIFT. The accuracy of pre- and postoperative 3D-US with 360° endoprobe (16 MHz) with automatic scanning and clinical findings was evaluated against surgical findings. Three outcomes were considered: healing, failure (persistent anal fistula through the original external opening or intersphincteric), and recurrence (reappearance of the anal fistula)., Results: Sixty-three patients of both sexes were evaluated. The 3D-US assessment revealed primary healing in 50 (79.3%) patients, although in 6 (9.5%) cases healing was delayed and the cavity was without communication with the anal canal. The procedure failed in 9 (15.9%) and fistula recurred in 4 (6.3%), all of whom underwent a second surgery based on a new 3D-US, resulting in a 92.3% (12/13) healing rate on 3D-US., Conclusions: A 3D-US was found to be useful in the preoperative assessment of fistulas by quantifying the percentage of muscle to be transected, and in the postoperative assessment by identifying healing, types of failure, and recurrence. The 3D-US was accurate and consistent with surgical findings., (© 2024 American Institute of Ultrasound in Medicine.)

Purpose: Corneal epithelial defects from trauma or surgery heal as new epithelial cells grow centripetally from the limbus and replenish the epithelium. Corneal wound healing requires cell signalling molecules. However, a topical treatment with these components is not available. Human breast milk (HBM) offers a potential, novel treatment as it contains bioactive molecules important in epithelial cell healing. This study seeks to investigate the potential of HBM in cornea wound healing., Methods: Balb/c mice, 8-12 weeks old, were anesthetized prior to creating a 2 mm central cornea epithelial defect. Mice were randomly assigned to a treatment group: HBM, ophthalmic ointment containing neomycin, polymyxin B, dexamethasone (RxTx), or saline and treated 4x/day for 2 days. Wound area was quantified by fluorescein and ImageJ at 0, 8, 24, and 48 h post wounding and eyes used for histology, RT-qPCR, and ELISA., Results: Wounded corneas treated with HBM demonstrated increased re-epithelialization at 8 h post injury compared to saline treatments. ELISA showed significantly higher Ki67 in HBM treated eyes vs. saline control at 8 h ( p =  0.0278). Additionally, immunohistology revealed more Ki67 positive cells in the HBM group compared to saline at 8 h and 24 h ( p  = 0.0063 8 h; p  = 0.0007 24 h). For inflammatory analysis, HBM group IL-1β levels were similar to the saline group, and higher than RxTx treated eyes ( p  < 0.05). Immunohistochemical staining for CD11b (macrophage marker) revealed HBM-treated eyes had significantly more positive cells vs. saline. RT-qPCR of limbal stem cell markers (LESCs) revealed upregulation of Integrin αV at 8 h with HBM vs. saline., Conclusions: HBM treatment on corneas with debridement of epithelium demonstrated improved healing, cellular proliferation, and upregulation of the LESC gene transcript, integrin αV, after wounding. Future studies could investigate LESC response to different signalling molecules in HBM to better understand the efficacy of this potential therapy.

Background: Pilonidal sinus disease impacts a patient's quality of life. In the Netherlands, it is often treated with excision and secondary wound healing, which is associated with high recurrence rates and poor wound healing. The Bascom cleft lift, an alternative technique, has shown favorable healing times and recurrence rates., Objective: The present study compares successful wound healing, time to healing, complications, and recurrence rate between excision with secondary wound healing and Bascom cleft lift., Design: This is a multicenter retrospective study., Settings: Three institutions in the Rotterdam region of the Netherlands participated in the study., Patients: Patients who underwent excision with secondary wound healing or Bascom cleft lift between July 2015 and August 2021 were included., Main Outcome Measures: Primary end points included the rate of successful wound healing and the time to achieve healing. Secondary end points included postoperative complications and the recurrence rate within 12 months after surgery., Results: Of 272 patients, 128 underwent Bascom cleft lift and 144 patients underwent excision and secondary wound healing. Recurrent pilonidal sinus disease (47.7% vs 22.2%) and abscess history (53.1% vs 40.3%) were more common in the Bascom cleft lift group compared to excision with secondary wound healing. The median follow-up period at the outpatient clinic was 43 days. The wound healing rate was 84.4% after Bascom cleft lift versus 32.6% after excision and secondary wound healing ( p < 0.001), with a median time to wound healing of 55 and 101 days, respectively ( p < 0.001). Complications were 28.9% for Bascom cleft lift versus 13.2% for excision and secondary wound healing ( p = 0.003). The rate of recurrent disease was 6.3% after Bascom cleft lift and 11.8% after excision and secondary wound healing ( p = 0.113)., Limitations: This study used a retrospective design, which makes it prone to selection bias and residual confounding. In addition, the short follow-up period adds to these limitations because a longer follow-up period may better identify true recurrence rates. The absence of collected patient satisfaction data, which is currently a common scientific issue, is also a deficiency., Conclusions: This retrospective study shows that Bascom cleft lift is superior to excision and secondary wound healing, given the higher percentage of patients with successful wound healing within a shorter time. See Video Abstract ., Resultados Posoperatorios De La Elevacin De La Hendidura Tipo Bascom Versus La Escisin Con Cicatrizacin De La Herida Por Segunda Intensin Para La Enfermedad De Seno Pilonidal Un Anlisis Retrospectivo Multicntrico: ANTECEDENTES:La enfermedad de seno pilonidal afecta la calidad de vida del paciente. En los Países Bajos, a menudo se trata con escisión y cicatrización por segunda intensión, lo que se asocia con altas tasas de recurrencia y mala cicatrización de las heridas. La elevación de la hendidura de Bascom, una técnica alternativa, ha mostrado tiempos de curación y tasas de recurrencia favorables.OBJETIVO:El presente estudio tiene como objetivo comparar la cicatrización exitosa de la herida, el tiempo de cicatrización, las complicaciones y la tasa de recurrencia entre la escisión con cicatrización secundaria de la herida y la elevación de hendidura tipo Bascom.DISEÑO:Este es un estudio retrospectivo multicéntrico.AJUSTES:Tres instituciones en la región de Rotterdam de los Países Bajos participaron en el estudio.PACIENTES:Se incluyeron pacientes sometidos a escisión con cicatrización secundaria o elecación de la hendidura tipo Bascom entre julio de 2015 y agosto de 2021.PRINCIPALES MEDIDAS DE RESULTADO:Los resultados primarios incluyeron la tasa de curación exitosa de la herida y el tiempo para lograr la curación. Los resultados secundarios incluyeron complicaciones posoperatorias y tasa de recurrencia dentro de los doce meses posteriores a la cirugía.RESULTADOS:De 272 pacientes, 128 se sometieron a elevación de hendidura tipo Bascom y 144 pacientes a escisión y cicatrización secundaria. La ESP recurrente (47.7% frente a 22.2%) y los abscesos (53.1% frente a 40.3%) fueron más comunes en el grupo de elevación tipo Bascom en comparación con la escisión con cicatrización secundaria de la herida. La mediana del período de seguimiento en la consulta externa fue de 43 días. La cicatrización de la herida fue del 84.4 % después del lifting de Bascom frente al 32.6 % después de la escisión y la cicatrización secundaria (p < 0.001), con una mediana de tiempo hasta la cicatrización de la herida de 55 días y 101 días, respectivamente (p < 0.001). Las complicaciones fueron del 28.9% para el lifting tipo Bascom frente al 13.2% para la escisión y cicatrización secundaria (p = 0.003). La enfermedad recurrente fue del 6.3% después del lifting de hendidura tipo Bascom y del 11.8% después de la escisión y cicatrización secundaria (p = 0.113).LIMITACIONES:Diseño retrospectivo que lo hace propenso a sesgos de selección y confusión residual. Adicionalmente, el corto período de seguimiento del estudio aumenta aún más estas limitaciones, ya que un seguimiento más prolongado puede identificar mejor las verdaderas tasas de recurrencia. Por último, una deficiencia es la ausencia de datos recopilados sobre la satisfacción del paciente, lo que hoy en día es un problema científico común.CONCLUSIONES:Este estudio retrospectivo muestra que la elevación de hendidura tipo Bascom es superior a la escisión y cicatrización secundaria dado el mayor porcentaje de pacientes con curación exitosa de la herida en un tiempo más corto. (Traducción-Dr. Jorge Silva Velazco )., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Colon and Rectal Surgeons.)

Objective: Rarefaction of blood and lymphatic vessels in the skin has been reported in systemic sclerosis (SSc) (scleroderma). E26 transformation-specific-related factor (ERG) and Friend leukemia virus-induced erythroleukemia 1 (FLI-1) are important regulators of angiogenesis, but their role in lymphatic vasculature is lesser known. The goal of this study was to determine the role of ERG and FLI-1 in postnatal lymphangiogenesis and SSc lymphatic system defects., Methods: Immunofluorescence was used to detect ERG and FLI-1 in skin biopsy samples from patients with SSc and healthy controls. Transcriptional analysis of ERG or FLI-1-silenced human dermal lymphatic endothelial cells (LECs) was performed using microarrays. Effects of ERG and FLI-1 deficiency on in vitro tubulogenesis in human dermal LECs were examined using a Matrigel assay. ERG and FLI-1 endothelial-specific knockouts and ERG lymphatic-specific knockouts were generated to examine vessel regeneration in mice., Results: ERG and FLI-1 protein levels were reduced in the blood and lymphatic vasculature in SSc skin biopsy samples. ERG levels were shown to regulate genes involved in lymphatic vessel specification, including vascular endothelial growth factor receptor 3/FLT-4, lymphatic vessel endothelial hyaluronan receptor 1, SOX-18, and prospero homeobox 1 (PROX-1), whereas FLI-1 enhanced the function of ERG. The ERG-FLT-4 pathway regulated in vitro tubulogenesis in human LECs. Deficiency of ERG or FLI-1 similarly impaired the function of blood vessels in mice. However, only ERG deficiency affected the regeneration of lymphatic vessels during wound healing., Conclusion: ERG and FLI-1 are essential regulators of blood and lymphatic vessel regeneration. Deficiency of ERG and FLI-1 in SSc endothelial cells may contribute to the impairment of blood and lymphatic vasculature in patients with SSc., (© 2024 American College of Rheumatology.)

In this review we discuss how the mammalian interfollicular epidermis forms during development, maintains homeostasis, and is repaired following wounding. Recent studies have provided new insights into the relationship between the stem cell compartment and the differentiating cell layers; the ability of differentiated cells to dedifferentiate into stem cells; and the epigenetic memory of epidermal cells following wounding., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

We aimed to investigate whether there is clinical and MRI evidence of healing of lateral ligaments 6 weeks after acute lateral ankle sprain (LAS). We prospectively enrolled 18 participants (age 32.7 ± 7.5 years) who sustained an acute LAS and underwent conservative treatment. An ankle MRI was acquired up to 48 hours and 6 weeks following the LAS. A partial tear of the anterior talofibular ligament (ATFL) was observed in 10/18 and a complete tear in 8/18 of the patients. The calcaneofibular ligament (CFL) was partially torn in 11/18 and completely torn in 1/18 of the patients. The healing status, intensity, and thickness of the ligaments, Anterior Drawer Test (ADT), and FAOS scale were assessed. A control group (CG) was composed by 17 participants (age 40 ± 13.9 years). Six weeks after the LAS, 89% of the participants presented MRI evidence of ATFL healing. The repaired ATFL was thicker in comparison with the CG (p < .001). The cut-off of 2.5 mm for ATFL thickness in the 6th week maximized sensitivity (62.5%) and specificity (100%). CFL and PTFL presented 94% and 100% of healing signs, respectively. In the 6th week, 11/18 (61%) participants showed mild residual instability and a mean FAOS of 80 ± 11. The MRI revealed signs of the repair process in 89% of ATFL and 94% of CFL tears, 6 weeks after a moderate or severe LAS. The MRI findings were concomitant with enhancements in mechanical ankle stability and function., (Copyright © 2024 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Means of addressing technical challenges in forming gastrojejunostomy (GJ) anastomoses and maintaining their patency are sought., Objectives: Evaluation of preclinical feasibility and healing efficacy of a novel linear magnetic compression anastomosis (MCA) device to form a patent GJ versus sutured jejunal enterotomy (JE) sites in swine., Setting: Single-center veterinary testing facility., Methods: Feasibility of 3 prototype sizes (4, 6, and 8 cm) of a metal MCA device (MCAD) to form a patent GJ was evaluated over 6 weeks. A distal magnet was laparoscopically inserted in the jejunum, a proximal magnet was placed gastroscopically in the stomach; magnets were aligned to gradually form an anastomosis, self-detached, and be expelled. At necropsy, MCAs were assessed for patency and compared with JE tissues to evaluate wound healing., Results: MCADs aligned at the GJ location without complications. In 5/6 MCAD pairs, dislodgement occurred between 7 and 26 days; expulsion 13-31 days; 1 MCAD pair was retained in the stomach. At necropsy, all pigs were healthy, gaining a mean 15.0 kg. Anastomoses were not adequately patent in 2/4 pigs receiving the 4-cm or 6-cm MCADs because their linear length was too small. But, anastomoses of both pigs receiving the 8-cm MCADs maintained full patency. Minimal inflammation and fibrosis were seen in MCA specimens versus sutured enterotomies., Conclusions: A novel linear MCA device was feasible and effectively created a patent GJ anastomosis in swine with minimal inflammation and fibrosis. The MCAD may be appropriate for clinical evaluation., (Copyright © 2024 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Although rare, complications like skin dehiscence and necrosis after neurosurgery pose significant challenges by increasing the risk of infections spreading to the epidural, subdural, or intracerebral spaces. This retrospective, single-center study aims to assess the prior clinical courses, neuroplastic repair, and outcomes of  patients with skin defects following cranial neurosurgical procedures, and to outline our interdisciplinary reconstructive protocol., Methods: A retrospective analysis was performed on cranial surgeries conducted at the Department of Neurosurgery,  spanning from 2017 to 2023. Patients with skin defects requiring the combined expertise of neurosurgery and plastic surgery for effective treatment were included. The sizes of the skin defects were measured using intraoperative photographs analyzed with the freeware ImageJ software, version 2018. All patients provided informed consent for the surgeries. If informed consent was not possible due to neurological deterioration, consent was sought from adult representatives or next of kin except for acute circumstances. All patients admitted to our hospital agree to the pseudonymized use of their medical data and tissue specimens for research purposes in their treatment contract., Results: A cohort of 24 patients experiencing wound healing complications after neurosurgical procedures underwent a total of 29 interdisciplinary surgeries for the reconstruction of skin, dural, and bone defects.  After the neuroplastic surgery, 8 out of 24 patients (33.3%) developed surgical complications, with 6 of these requiring revision surgeries due to persistent cranial infection.  In all cases,  permanent wound closure was successfully achieved following adherence to the proposed treatment algorithm., Conclusions: Our study underscores the necessity of an integrated neurosurgical and plastic surgical approach to effectively manage wound healing complications in a single stage surgery. Key interventions include differentiation between necrosis and gaping lesions, alongside precise management of neurosurgical issues like cerebrospinal fluid fistulas and hydrocephalus. Plastic surgical expertise in assessing the possibilities and limitations of both local and free flap surgeries is essential., (© 2024. The Author(s).)

Aim: The aim of the study was to evaluate the trabeculation increase of treated mandibular cysts., Material and Method: The study included 26 female and 33 male patients (age mean: 38,4 years) with cysts larger than 3 cm in the posterior region of the mandible who were admitted to the same center. Two groups in treatment technique: marsupialization (n = 29) and enucleation (n = 30). Four groups in cyst types: dentigerous cyst (n = 21), keratocyst (n = 19), radicular cyst (n = 15) and residual cyst (n = 4). Cyst size was divided into two categories: smaller than 5.5 cm (n = 31) and larger than 5.5 cm (n = 28). Panoramic radiographs (PR) of the patients were analyzed at the beginning, 6. month and 12. month., Result: At the end of the treatment, there was no statistically significant difference in terms of Fractal Analysis (FA) between patients treated with marsupialization and enucleation, but considering that the cysts in the marsupialization group were larger in size, a faster increase in FA was observed in the marsupialization group. When the cysts were grouped according to their size, it was observed that healing tissues in cysts smaller than 5.5 cm reached normal FA values faster, while healing in the middle of cysts larger than 5.5 cm took more time., Conclusions: FA is a reproducible and reliable method. In large cysts, marsupialization results in a faster recovery, but FA values at the end of treatment are similar to the enucleation group. Cysts larger than 5.5 cm show a more rapid increase in Fractal Dimension (FD). The centre of the cysts is the area that heals the latest. Studies with larger sample sizes are needed to evaluate the difference in healing between cyst types., Clinical Trial Number: Clinical trial number: Not applicable., (© 2024. The Author(s).)

Sports medicine physicians and physiotherapists commonly use cryotherapy (eg, ice application) postinjury to decrease tissue temperature with the objective of reducing pain, limiting secondary injury and inflammation, and supporting healing. However, besides the analgesic effect of cryotherapy, a literature search revealed no evidence from human studies that cryotherapy limits secondary injury or has positive effects on tissue regeneration. Thus, our current understanding of the potential mechanisms and applications of cryotherapy largely relies on the results from animal studies. Importantly, treatment should not aim at obliterating the inflammatory and regeneration processes but instead aim to restore an adapted/normal regulation of these processes to improve function and recovery. However, some animal studies suggest that cryotherapy may delay or impair tissue regeneration. With the translation of laboratory animal studies to human sport medicine being limited by different injury and muscle characteristics, the effect of cryotherapy in patients with musculoskeletal injuries is uncertain. Thus, pending the results of human studies, cryotherapy may be recommended in the first 6 hours following an injury to reduce pain (and possibly haematoma), but it should be used with caution beyond 12 hours postinjury as animal studies suggest it may interfere with tissue healing and regeneration., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Keratin intermediate filaments confer structural stability to epithelial tissues, but the reason this simple mechanical function requires a protein family with 54 isoforms is not understood. During skin wound healing, a shift in keratin isoform expression alters the composition of keratin filaments. If and how this change modulates cellular functions that support epidermal remodeling remains unclear. We report an unexpected effect of keratin isoform variation on kinase signal transduction. Increased expression of wound-associated keratin 6A, but not of steady-state keratin 5, potentiated keratinocyte migration and wound closure without compromising mechanical stability by activating myosin motors to increase contractile force generation. These results substantially expand the functional repertoire of intermediate filaments from their canonical role as mechanical scaffolds to include roles as isoform-tuned signaling scaffolds that organize signal transduction cascades in space and time to influence epithelial cell state., Competing Interests: Declaration of interests G.D. is a member of the advisory board to Developmental Cell., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Neurogenic bladder often occurs after pelvic ganglia injury. Its symptoms, like severe urinary retention and incontinence, have a significant impact on individuals' quality of life. Unfortunately, there are currently no effective treatments available for this type of injury. Here, we designed a fiber-enhanced tissue bandage for injured pelvic ganglia. Tight junctions formed in tissue bandages create a mini tissue structure that enhances resistance in an in vivo environment and delivers growth factors to support the healing of ganglia. Strength fibers are similar to clinical bandages and guarantee ease of handling. Furthermore, tissue bandages can be stored at low temperatures over 5 months without compromising cell viability, meeting the requirements for clinical products. A tissue bandage was applied to a male rat with a bilateral major pelvic ganglia crush injury. Compared to the severe neurogenic bladder symptoms observed in the injury and scaffold groups, tissue bandages significantly improved bladder function. We found that tissue bandage increases resistance to mechanical injury by boosting the expression of cytoskeletal proteins within the major pelvic ganglia. Overall, tissue bandages show promise as a practical therapeutic approach for ganglia repair, offering hope for developing more effective treatments for this thorny condition., (© 2024. The Author(s).)

Wound closure after brain injury is crucial for tissue restoration but remains poorly understood at the tissue level. We investigated this process using in vivo observations of larval zebrafish brain injury. Our findings show that wound closure occurs within the first 24 h through global tissue contraction, as evidenced by live-imaging and drug inhibition studies. Microglia accumulate at the wound site before closure, and computational models suggest that their physical traction could drive this process. Depleting microglia genetically or pharmacologically impairs tissue repair. At the cellular level, live imaging reveals centripetal deformation of astrocytic processes contacted by migrating microglia. Laser severing of these contacts causes rapid retraction of microglial processes and slower retraction of astrocytic processes, indicating tension. Disrupting the lcp1 gene, which encodes the F-actin-stabilising protein L-plastin, in microglia results in failed wound closure. These findings support a mechanical role of microglia in wound contraction and suggest that targeting microglial mechanics could offer new strategies for treating traumatic brain injury., (© 2024 El-Daher et al.)

Background: Traditional reconstructive options of fingertip injuries are technically difficult, usually need donor site skin grafting, leave visible scars, and need a protracted period of finger immobilization resulting in joint stiffness. Electro-photobiomodulation (EPBM), is the process of combining intense pulsed light and radiofrequency to modify tissues to help the body heal itself, lower inflammation, and promote wound healing., Patients and Methods: This study included 60 patients presented with fingertip injuries. Patients were randomly divided into two groups. Group 1 includes patients who were treated by EPBM. Group 2 includes patients who were treated by cross finger flap (CFF). Six months after complete healing, evaluation was performed for aesthetic and functional outcome and patient satisfaction., Results: Compared to group 2 patients, group 1 patients had statistically significant better sensory outcome, better total active motion of affected digits, grip strength, patient satisfaction, healing time, and plastic surgeon general aesthetic evaluation and also, they had statistically significant less adverse events and cold intolerance with absent donor site pain and deformity., Conclusion: EPBM is safe and effective treatment of fingertip injuries which shortens the healing time, produces the best aesthetic and functional result while avoiding donor site morbidity of the traditional reconstructive options., (© 2024. The Author(s).)

Background and Objectives : Complex wounds in the hand and distal lower extremities pose challenges in reconstructive surgery, often involving critical structures like tendons. Tendon injuries, prevalent in such wounds, necessitate optimal repair methods for functional recovery. This study investigates the impact of vascularised and nonvascularised adipofascial tissue on tendon repair, focusing on early healing stages, mobilisation, and scintigraphic evaluation of flap vascularity. Materials and Methods: Wistar Albino rats were divided into groups undergoing primary tendon repair, vascularised adipofascial flap application, or nonvascularised flap application. Scintigraphic evaluation and histopathological assessment were performed to analyse healing processes. Results : Pedicle-free flaps support healing in tendon injuries without negatively affecting medium-term outcomes. Vascularised flaps exhibit faster healing. The scintigraphic analysis showed that the static measurements of the late phase were statistically significantly higher in the group with the non-vascularised adipofascial flap ( p = 0.038). The mean perfusion reserve was higher in the vascularised pedicled adipofascial flap group than the non-vascularised adipofascial flap group. Scintigraphic analysis highlights the viability of pedicle-free flaps. Conclusions : Pedicle-free adipofascial flaps support the healing of the tendon without complicating the results, while vascularised flaps show accelerated healing. These findings provide valuable insights into optimising tendon repair strategies using adipofascial flaps, with implications for enhancing functional recovery in complex wounds.

Objective: Given the increasing demand for precise and reliable reconstructive techniques in maxillofacial surgery, we try to offer valuable insights for clinicians in selecting optimal fixation methods., Materials and Methods: Patients were categorized into miniplate and reconstruction plate groups for accuracy and bone healing comparison. We measured gonial angle, intercondylar, intergonial and anterior-posterior distance for general accuracy and distance of segmental endpoint to the sagittal plane for partial accuracy. The bone healing rate of the two groups was compared with CT images at 3, 6 and 12 months after operation., Result: Considering directional indicators, the miniplate group exhibited a wider intercondylar distance than the reconstruction plate group (p = 0.029). At 6 months postoperatively, the miniplate group demonstrated a higher bone healing rate compared to the reconstruction plate group, with no significant differences at other time points., Conclusion: Over a nearly 5-year review, mandibular reconstruction with vascularized iliac bone flaps showed that reconstruction plates better maintained condylar position accuracy, while miniplates had superior bone healing rates at 6 months. No significant differences were found in other accuracy indices between the two plates., Clinical Relevance: Clinicians' selection of fixation plates frequently depends on personal preference rather than evidence-based criteria. This study compares the precision and postoperative osseous healing outcomes of miniplates and reconstruction plates to provide a more scientifically grounded basis for clinical decision-making., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Suturing techniques for wound closure in spine surgeries play a critical role in patient outcomes, including wound healing, reintervention, and risk of complications. Barbed sutures, characterized by their self-anchoring properties, have emerged as a potential alternative to conventional sutures in various surgical disciplines. While previous studies have underscored their efficacy and safety in spine surgeries, no meta-analysis has been conducted. Therefore, we are undertaking this study. Following the PRISMA guidelines, we conducted a literature search on electronic databases to obtain the relevant studies until May 5, 2024. Our primary outcomes were operative time, wound closure time, and postoperative wound complications like seroma or hematoma formation and wound infection. The secondary outcomes were the length of hospital stay, reintervention rates, and costs. Data was pooled using a random effects model. We included seven eligible studies with a total of 8645 patients. Our meta-analysis showed that barbed sutures had shorter operative time and wound closure time compared to conventional sutures (MD -20.13 min, 95% CI [-28.47, -11.78], P < 0.001) and (MD -16.36 min, 95% CI [-20.9, -11.82], P < 0.001), respectively. Both suturing techniques showed comparable results in terms of overall postoperative wound complications (RR 0.83, 95% CI [0.60, 1.14], P = 0.25), postoperative infections (RR 0.59, 95% CI [0.33, 1.06], P = 0.08), length of hospital stay (MD -0.26 day, 95% CI [-0.75, 0.22], P = 0.28), rates of reintervention between the two groups (RR 0.99, 95% CI [0.48, 2.05], P = 0.98). Barbed sutures in spine surgeries are associated with significantly shortened wound closure and operative times. However, high-quality RCT's with long-term follow-up and cost-effectiveness assessment are required to support the evidence., (© 2024. The Author(s).)

Coral reefs, among the most diverse ecosystems on Earth, currently face major threats from pollution, unsustainable fishing practices , and perturbations in environmental parameters brought on by climate change. Corals also sustain regular wounding from other sea life and human activity. Recent reef restoration practices have even involved intentional wounding by systematically breaking coral fragments and relocating them to revitalize damaged reefs, a practice known as microfragmentation. Despite its importance, very little research has explored the inner mechanisms of wound healing in corals. Some reef-building corals have been observed to initiate an immunological response to wounding similar to that observed in mammalian species. Utilizing prior models of wound healing in mammalian species as the mathematical basis, we formulated a mechanistic model of wound healing, including observations of the immune response and tissue repair in scleractinian corals for the species Pocillopora damicornis. The model consists of four differential equations which track changes in remaining wound debris, number of cells involved in inflammation, number of cells involved in proliferation, and amount of wound closure through re-epithelialization. The model is fit to experimental wound size data from linear and circular shaped wounds on a live coral fragment. Mathematical methods, including numerical simulations and local sensitivity analysis, were used to analyze the resulting model. The parameter space was also explored to investigate drivers of other possible wound outcomes. This model serves as a first step in generating mathematical models for wound healing in corals that will not only aid in the understanding of wound healing as a whole, but also help optimize reef restoration practices and predict recovery behavior after major wounding events., Competing Interests: Declaration of competing interest None, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Objectives: Remodeling and healing of the graft are crucial processes for long-term graft survival after anterior cruciate ligament reconstruction (ACLR). However, few studies have objectively evaluated the differences in graft healing between autografts and allografts. This study aimed to compare the status of the anterior cruciate ligament (ACL) grafts between hamstring tendon (HT) autografts and tibialis anterior tendon (TAT) allografts using second-look arthroscopy. Materials and Methods: The outcomes of 193 consecutive patients (153 males and 40 females, with an average age of 30.38 and BMI of 25.43 kg/m 2 ) who underwent second-look arthroscopy following primary ACLR were retrospectively reviewed. Prior to participating in this study, all patients provided written informed consent. The patients were divided into two groups: those with HT autografts and those with TAT allografts. Confounding factors were matched between the two groups using propensity score matching (PSM). ACL graft status was assessed during second-look arthroscopy using a numeric scale system based on the degree of four parameters: graft tension, continuity, synovium coverage, and vascular marking. Clinical outcomes were assessed using the Lysholm and International Knee Documentation Committee (IKDC) scores. Graft status and clinical outcomes were compared between the two groups. Additionally, a subgroup analysis based on the timing of the second-look arthroscopy (12-24 months vs. >24 months after the initial ACLR) was conducted. Results: After PSM, 62 patients were included in each group. The second-look arthroscopy was conducted at 23.6 ± 6.6 months for the HT group and at 24.0 ± 7.9 months for the TAT group ( p = 0.749). The continuity and tension of the ACL graft were not significantly different between the two groups ( p = 0.146 and 0.075, respectively). However, the TAT group exhibited significantly inferior synovial coverage and vascular marking of the ACL graft compared with the HT group ( p = 0.021 and 0.007, respectively). These findings were consistent regardless of the timing of the second-look arthroscopy. Clinical outcomes, according to the Lysholm and IKDC scores, significantly improved in both groups with no significant differences ( p = 0.386 and 0.733, respectively). Conclusions: Although there were no differences in graft tension and continuity between HT autografts and TAT allografts, the biological healing of ACL grafts, in terms of synovialization and vascularization, was superior in HT autografts compared to TAT allografts.

The reliability of cellular migration measurement in wound healing assays is frequently undermined by the prevalent methodological instability, i.e., tip-based method. We introduce an innovative instrument designed to address these limitations. Our novel cell scraper surpasses the current approach, generating a more consistent and stable cell-free gap. Repeated biological experiments reveal that the cell-free gap produced by the cell scraper exhibits straighter edges and uniform size and shape compared to the tip-based technique (p < 0.05). In terms of product design, the cell scraper boasts a refined color scheme suited for laboratory environments, enhancing the monitoring of experimental outcomes, and permits sterilization through autoclaving for reuse. Notably, after treatment, the cell scraper demonstrates a negligible effect on cell viability and proliferation (97.31% and 24.41%, respectively). Conversely, the tip-based method yields lower cell viability (91.37%) and proliferation (18.79%). This investigation presents the cell scraper as a novel, reusable device capable of generating reproducible cell-free gaps while preserving cellular viability, thereby augmenting the reliability of wound healing assays in comparison to existing techniques.

General Purpose: To review the role of nutrition and high-quality dietary protein intake in creating healthy granulation tissue and optimize wound healing in patients with chronic wounds., Target Audience: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and registered nurses with an interest in skin and wound care., Learning Objectives/outcomes: After participating in this educational activity, the participant will:1. Summarize the structure and composition of proteins. 2. Specify the role of proteins in generating healthy granulation tissue and wound healing. 3. Explain the physiologic pathways involved in the wound healing process. 4. Describe evidence-based interventions to support nutrition in wound healing., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Axillary osmidrosis (AO), the condition of armpit smell, can be treated with minimally invasive techniques. However, patients may experience wound complications and a relatively long recovery period after operation. In this case series, the researchers investigated the effectiveness of systematic wound management for wound healing after minimally invasive treatment of AO.From January 2016 to December 2021, 64 patients with AO underwent systematic wound management after minimally invasive treatment. Systematic wound management included three consecutive steps of wound irrigation with 0.9% sodium chloride, suction drainage, and compression dressing. The researchers retrospectively evaluated wound healing results and recorded complications. Of the patients, 60 (93.8%) had good primary wound healing results, 1 (1.5%) developed a hematoma, and 3 (4.7%) had partial epidermis necrosis. The hematoma was easily evacuated, and the partial epidermis necrosis recovered spontaneously without obvious scarring. No other adverse effects were observed.The results of this case series indicate that systematic wound management is reliable and practical and provides good wound healing results after minimally invasive treatment of AO., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To study the effect of physical plasma jet in treating open wounds in diabetic and non-diabetic dogs., Methods: The experimental study was conducted at the College of Veterinary Medicine, University of Baghdad, Iraq, from 20 January, 2020 to 1st May 2020, according to (no. 1364/ P.G), and comprised adult male diabetic and nondiabetic dogs. They were divided into non-diabetic group N and diabetic group D. Each group was further divided into treatment subgroup T and control subgroup C. Each dog was subjected to 4 wounds 3×3cm in size. Homemade helium non-equilibrium atmospheric pressure plasma jet therapy was used for healing purposes. Clinical parameters were evaluated by observation, while histological images were scored based on the semi-quantitative evaluation of histological sections on days 3-, 7- and 21-days post-wound. Data was analysed using SPSS Version 26 with One-way ANOVA for statistical analysis between groups and sub-groups., Results: Of the 24 dogs, 12(50%) were in each of the two groups, which were further divided into subgroups having 6(50%) dogs each. The therapy accelerated the process of wound healing in the NT and DT subgroups compared to NC and DC. Clinical observations revealed early and complete closure of plasma-treated wounds in NT and DT subgroups started at day 30 post-wounding, while in the NC subgroup it started at day 35, and in the DC subgroup, wounds failed to close even after 35 days post-wounding. Histological analysis suggested that a plasma jet supported epithelisation, angiogenesis, formation of new hair follicles and collagen fibres, while it also controlled inflammation. In addition, in NT and DT subgroups, it increased the proliferation of fibroblasts and deposition of collagen, and there is a very, highly significant difference between groups (P<0.001), and a significant difference between days (P<0.05)., Conclusions: Home-made helium non-equilibrium atmospheric pressure plasma jet therapy improved the quality and pace of wound healing.

Photorefractive keratectomy (PRK) was the first excimer laser procedure developed to treat refractive errors. The safety and efficacy of PRK established it as one of the most performed corneal refractive procedures worldwide. With the introduction of laser in situ keratomileusis (LASIK), and more recently keratorefractive lenticule extraction (KLEx) procedures, many corneal surgeons favor these newer corneal procedures as the first choice due to faster visual rehabilitation and less discomfort during the early postoperative period. Importantly, however, PRK remains a viable alternative for most corneal refractive candidates and there are many situations in which PRK remains the refractive procedure of choice. This review addresses the technical evolution of PRK-mechanical epithelial debridement versus alcohol-assisted epithelial removal versus excimer laser-assisted epithelial debridement (transepithelial) PRK-and reports the PRK refractive outcomes compared to other keratorefractive laser procedures. The corneal wound response associated with each PRK technique and the indications, limitations, and complications of PRK are reviewed to aid refractive surgeons to best position PRK in their overall practice. [ J Refract Surg . 2024;40(10):e754-e767.] .

The cutaneous microbiome represents a highly dynamic community of bacteria, fungi and viruses. Scientific evidence, particularly from the last two decades, has revealed that these organisms are far from being inconsequential microscopic hitchhikers on the human body, nor are they all opportunistic pathogens waiting for the chance to penetrate the skin barrier and cause infection. In this review, we will describe how dermatological diseases have been found to be associated with disruptions and imbalances in the skin microbiome and how this new evidence had shaped the diagnosis and clinical practice relating to these disorders. We will identify the microbial agents which have been found to directly exacerbate skin diseases, as well as those which can ameliorate many of the symptoms associated with dermatological disorders. Furthermore, we will discuss the studies which suggest that bacteriotherapy, either by topical use of probiotics or by bacteria-derived compounds, can rectify skin microbial imbalances, thereby offering a promising alternative to antibiotic treatment and reducing the risks of antibiotic resistance., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Negative pressure wound therapy (NPWT) and antibiotic-loaded bone cement (ALBC) are commonly used treatments for diabetic foot ulcers (DFUs). However, the combined efficacy of these two modalities remains unclear. This clinical study aimed to assess the effectiveness and underlying mechanisms of NPWT&ALBC in the management of DFUs. A total of 28 patients were recruited, 16 of whom served as controls and received only NPWT, whilst 12 received NPWT&ALBC. Both groups underwent wound repair surgery following the treatments. Blood samples were obtained to detect infections and inflammation. Wound tissue samples were also collected before and after the intervention to observe changes in inflammation, vascular structure and collagen through tissue staining. Compared with the NPWT group, the NPWT&ALBC group exhibited a superior wound bed, which was characterised by reduced inflammation infiltration and enhanced collagen expression. Immunostaining revealed a decrease in IL-6 levels and an increase in α-SMA, CD68, CD206 and collagen I expression. Western blot analysis demonstrated that NPWT&ALBC led to a decrease in inflammation levels and an increase in vascularization and collagen content. NPWT&ALBC therapy tends to form a wound bed with increased vascularization and M2 macrophage polarisation, which may contribute to DFUs wound healing., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Competing Interests: Honorare für Beratungen, Vorträge und/oder Studien: Institut AllergoSan, BEMER Inc., Curea medical, DebeX, essity, Schülke und Mayr, Serag und Wiessner, Smith und Nephew, URGO

In recent years, systemic inflammation has emerged as a pivotal player in the development and progression of various degenerative diseases. This complex, chronic inflammatory state, often undetected, can have far-reaching consequences for the body's physiology. At the molecular level, markers such as C-reactive protein, cytokines and other inflammatory mediators serve as indicators of systemic inflammation and often act as predictors of numerous musculoskeletal diseases and even certain forms of cancer. The concept of 'meta-inflammation', specifically referring to metabolically triggered inflammation, allows healthcare professionals to understand inflammatory responses in patients with metabolic syndrome. Driven by nutrient excess and the expansion of adipose tissue, meta-inflammation is closely associated with insulin resistance, further propagating the metabolic dysfunction observed in many Western societies. Wound persistence, on the other hand, exacerbates the detrimental effects of prolonged inflammation at the local level. Acute inflammation is a beneficial and essential process for wound healing and infection control. However, when inflammation fails to resolve, it can impede the healing process, leading to chronic wounds, excessive scarring and even the activation of fibrotic pathways. This approach significantly reduces the efficacy of regenerative biological therapies. Our review focuses on the vital role of proteins, vitamins and minerals in collagen synthesis and cell proliferation for tissue healing. We also examine hormonal influences on regeneration, noting the negative effects of imbalances, and emphasize glucose regulation's importance in creating a stable environment for chronic wound healing., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Previous studies have implicated epithelial-mesenchymal transition (EMT) in salamander limb regeneration. In this review, we describe putative roles for EMT during each stage of limb regeneration in axolotls and other salamanders. We hypothesize that EMT and EMT-like gene expression programs may regulate three main cellular processes during limb regeneration: (1) keratinocyte migration during wound closure; (2) transient invasion of the stump by epithelial cells undergoing EMT; and (3) use of EMT-like programs by non-epithelial blastemal progenitor cells to escape the confines of their niches. Finally, we propose nontraditional roles for EMT during limb regeneration that warrant further investigation, including alternative EMT regulators, stem cell activation, and fibrosis induced by aberrant EMT., (© 2024 The New York Academy of Sciences.)

Healing process in the oral cavity is influenced by a range of systemic factors. More specifically, patient health status, medications, habits, and nutritional state play crucial roles in dental healing. Additionally, the body's immune response, inflammation, and overall well-being are key determinants in wound repair. Understanding these systemic factors is essential for dental professionals to optimize patient care, minimize complications, and achieve successful healing., Competing Interests: Disclosure M. Fatahzadeh, A. Ravi, P. Thomas, and V.B. Ziccardi declare no conflict of interest. Statement of institutional review board approval or waiver: Institutional review and approval were not necessary for this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Indocyanine green (ICG) angiography for the intraoperative evaluation of tissue perfusion is commonly used in implant-based breast reconstruction (IBR). The assessment of ICG images depends on the surgeon's interpretation and is qualitative or semiqualitative in nature. To quantify ICG metrics, this study aimed to apply a novel assessment of fill-rate dynamics to predict wound-healing complications and provide pragmatic assessment tools in IBR., Methods: This was a retrospective cohort study of patients who underwent IBR with ICG using the photodynamic eye (PDE-Neo II) qualitative imaging system between April 2021 and September 2023. ICG recordings were reviewed to quantify the relative surface area and fluorescence intensity of visual perfusion deficits using ImageJ. The primary outcome was the incidence of wound-healing complications. t-tests and logistic regression were performed for statistical testing., Results: A total of 112 patients (201 breasts) were included. The incidence of wound-healing complications was 12.9%. A higher relative surface area of ischemic regions was significantly associated with wound-healing complications (3.3% vs. 0.90%; p = 0.001). The rate of change in the surface area of ischemic regions was significantly associated with wound-healing complications (0.35% per second vs. 1.29% per second; p = 0.003%). On average, the duration of transient ischemic areas was significantly longer in breasts with wound-healing complications (46.0 s vs. 36.0 s, p = 0.01)., Conclusion: A transient ischemic area of > 5% of the breast and/or failure to resolve transient ischemic areas after 60 s may predict wound-healing complications and inform surgical reconstructive decision-making in IBR., (Published by Elsevier Ltd.)

Background: Circumcision of a male child is an integral part of some African cultures. An ideal technique of neonatal circumcision should be simple, safe and heal satisfactorily with good cosmetic appeal. The aim was to compare conventional dissection (CD), Plastibell (PB) and Gomco (GM) techniques of circumcision in neonates in terms of wound healing, wound healing complications, cosmetic outcome and parental satisfaction., Materials and Methods: A total of 144 male neonates were randomised into three study groups: CD, GM and PB groups. All procedures were performed under local anaesthesia as day case. Superficial wound healing was assessed on the 7 th post-operative day. The cosmetic outcome of the three techniques was assessed by a plastic surgeon and the parents using a 4-point Likert scale on the 4 th post-operative week., Results: The three groups were comparable in terms of age ( P = 0.207) and weight ( P = 0.098) at circumcision. There was satisfactory wound healing in 48 (100%) patients in the GM group, compared to 47 (97.8%) in the CD group and 45 (93.8%) in the PB group ( P = 0.324). Wound healing complications were recorded in seven patients, 1 (2.1%) in the CD group with wound infection, 5 (10.4%) in the PB group with moderate pain despite the use of analgesia and 1 (2.1%) patient with skin bridge in the CD group. The plastic surgeon and the parents rated the cosmetic outcome of CD higher than the other two techniques., Conclusion: There is no significant difference in superficial wound healing amongst the three circumcision techniques. The cosmetic outcome of CD was significantly better than that of GM and PB circumcisions., (Copyright © 2024 Copyright: © 2024 African Journal of Paediatric Surgery.)

Autologous adipose tissue was recognized as a promising therapeutic option for soft tissue defects owing to its regenerative potential and ability to facilitate tissue reconstruction. However, the mechanisms by which autologous fat grafting (AFG) promotes healing remain unclear, hindering its potential applications. This study aimed to investigate the distribution and phenotypic transition of infiltrating macrophages in transplanted adipose tissue, as well as their correlation with diabetic skin defect remodeling. Streptozotocin-induced diabetic rats with full-thickness dorsal skin defects were included in this study. The transplanted adipose tissue at the skin defects was collected and analyzed using flow cytometry to determine macrophage proportion and phenotype. The healing of skin defects was evaluated, and treatment was continued until day 14 as the designated endpoint of healing, followed by histopathologic examinations. Immunostaining with CD31 and lymphatic vessel endothelial receptor-1 was performed on wound tissues to analyze angiogenesis and lymphangiogenesis, respectively. Western blot and quantitative polymerase chain reaction analyses were used to assess the expression of the representative genes involved in the healing process. The results showed early polarization of M2 macrophages in the transplanted adipose tissue, concomitant with the upregulation of growth factors and downregulation of inflammatory factors. In vivo experiments revealed that AFG significantly promoted macrophage infiltration and M2 transformation in diabetic skin defects compared to the control groups, thereby promoting tissue extracellular matrix remodeling and lymphatic and vascular regeneration. However, the beneficial effects of AFG were inhibited by macrophage depletion. This study further demonstrated the potential of AFG for treating diabetic skin defects., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Abstract: The human body possesses the unique ability to repair itself after injury through complex, sequential phases. Current development of advanced wound care therapies generally focuses on addressing a single aspect of this biological process that can result in delayed or ineffective wound healing. When patients present with further systemic and local confounding pathologies, it can result in painful, chronic wounds that are especially challenging to treat.In this case report, the authors demonstrate how treatment with a novel multimodal wound matrix expedited healing and decreased pain in two patients who had each been unresponsive to treatment with advanced modalities for more than 7 months. The first patient had factor V Leiden, and the second patient had sickle cell disease. Use of a once-weekly treatment protocol with the multimodal wound matrix, combined with sharp debridement when deemed clinically necessary, resulted in elimination of pain and expedited wound healing to closure. The wound matrix's omega fatty acid-based formulation is designed to target multiple factors common among hard-to-heal wounds that when not addressed can adversely inhibit the wound-healing cascade., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Due to their tissue structure similar to mammalian skin and their close evolutionary relationship with chordates, holothurians (Echinodermata: Holothuroidea) are particularly interesting for studies on wound healing. However, previous studies dealing with holothuroid wound healing have had limited approaches, being restricted to tissue repair or perivisceral immune response. In this study, we combined tissue, cellular and humoral parameters to study the wound healing process of Holothuria grisea. The immune responses of the perivisceral coelom were assessed by analyzing the number, proportion and viability of coelomocytes and the volume and protein concentration of the coelomic fluid. Additionally, the morphology of the healing tissue and number of coelomocytes in the connective tissue of different body wall layers were examined over 30 days. Our results showed that perivisceral reactions started 3 h after injury and decreased to baseline levels within 24 h. In contrast, tissue responses were delayed, beginning after 12 h and returning to baseline levels only after day 10. The number of coelomocytes in the connective tissue suggests a potential cooperation between these cells during wound healing: phagocytes and acidophilic spherulocytes act together in tissue clearance/homeostasis, whereas fibroblast-like and morula cells cooperate in tissue remodeling. Finally, our results indicate that the major phases observed in mammalian wound healing are also observed in H. grisea, despite occurring at a different timing, which might provide insights for future studies. Based on these data, we propose a model that explains the entire healing process in H. grisea., Competing Interests: Declaration of competing interest The authors declare that they have no known competing interests or personal relationships that could have appeared to influence the work reported in this study., (Copyright © 2023. Published by Elsevier Inc.)

Objective: Chronic wound healing is a complex process that is still not well understood. The tryptophan (TRP)-l-kynurenine (KYN) pathway has recently been under increased scrutiny with regard to wound healing. The study applied metabolomics to elucidate the TRP-l-KYN pathway associated with wound healing in chronic venous leg ulcers (CVLUs). Approach: This study used a longitudinal comparative design of 60 serum samples collected from 30 older adult patients with CVLUs, receiving weekly sharp debridement at a wound clinic. The serum samples were collected at baseline and week 4 (healed wounds) or week 8 (nonhealed wounds). Liquid chromatography-mass spectrometry (LC-MS) metabolomics was used to analyze targeted metabolites. A Bayesian approach was used to examine robust correlations between changes in metabolite values and linear healing slope and to compare by group. Results: The mean age was 71.13 (±9.46 years). Half of the sample were female and the minority (17%) were Black. The mean values of evaluated metabolites for the nonhealed group were consistently lower than those for the healed group. The healed group ( n = 12) had higher KYN values. Those on a healing trajectory ( n = 23) had lower KYN levels and higher TRP levels at baseline and over time. There was moderate support (Bayes factor = 3.70) for a negative association between change in kynurenic acid and linear healing slope ( r = -0.35, credibility intervals [CrI] = -0.62, -0.04; probability of direction [PD] = 98%). Results suggest that KYN and TRP may be markers for healing in individuals with CVLUs. Innovation and Conclusion: Gaining a better understanding of the associations between the TRP-l-KYN pathway and the healing of CVLUs may help to clarify the links of inflammation with the rate and success of wound healing. Biomarker development focused on the TRP-l-KYN pathway could be pursued, if the associations are further supported by focused research studies.

Aim: This study aimed to assess hard and soft tissue contour changes following micro crestal flap-alveolar ridge preservation (MCF-ARP) and natural healing (NH) in periodontally compromised molar extraction sites and to analyse the feasibility and need for bone augmentation during implant therapy., Materials and Methods: Fifty-six patients with 70 sites were randomized into two groups at the site level (35 sites from 31 patients in the test group and 35 sites from 29 patients in the control group). Among whom, four patients contributed one tooth to the control group and one tooth to the test group. Hard tissue indicators were measured using cone beam computed tomography performed before tooth extraction and 6 months after surgery. Soft tissue contour changes were assessed using intraoral scanning performed before and immediately after surgery and also 2 weeks and 1, 3 and 6 months after surgery., Results: Six months after surgery, the MCF-ARP group showed less resorption in buccal bone height (p = .032) and greater augmentation in central bone height (p = .001) and ridge width (p = .009). The mean, vertical and horizontal collapse of buccal soft tissue contour in the MCF-ARP group were 0.95 mm (p = .010), 0.61 mm (p = .019) and 0.56 mm (p = .013) less than that in the NH group, respectively. There were significantly (p = .007) fewer sites in the MCF-ARP group than in the NH group (0% vs. 26.7%) for staged bone augmentation and more sites that could be treated with simple implant procedure in the MCF-ARP group than in the NH group (71.9% vs. 56.6%)., Conclusions: Compared with NH, MCF-ARP reduced bone resorption in periodontally compromised molar extraction sites and maintained the buccal soft tissue contour. MCF-ARP reduces the need for complex bone augmentation procedures in implant therapy., Trial Registration: Chinese Clinical Trial Register (ChiCTR) ChiCTR2200056335. Registered on 4 February 2022, Version 1.0., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Wounds are the common fates in various microbial infections and physical damages including accidents, surgery, and burns. In response, a healthy body with a potent immune system heals that particular site within optimal time by following the coagulation, inflammation, proliferation, and remodeling phenomenon. However, certain malfunctions in the body due to various diseases particularly diabetes and other physiological factors like age, stress, etc., prolong the process of wound healing through various mechanisms including the Akt, Polyol, and Hexosamine pathways. The current review thoroughly explains the wound types, normal wound healing mechanisms, and the immune system's role. Moreover, the mechanistic role of diabetes is also elaborated comprehensively., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Amniotic membrane, derived from the innermost placenta, is widely employed in surgery to help regenerate soft tissue and promote re-epithelialization. The authors detail a case report of a 59-year-old female who presented with a large, full-thickness scalp avulsion injury (13 × 10 cm) after being attacked by her pet pitbull. Innovative application of "snowflake" or fragmented amniotic membrane to her wound bed was used during both stages of scalp reconstruction: irrigation and debridement with Integra biological membrane placement and later split-thickness skin grafting. The patient had an uncomplicated recovery with a satisfactory cosmetic outcome. The authors believe that the "snowflake" application of amniotic membrane played an important role in forming healthy granulation tissue and optimizing the wound bed for definitive coverage. "Snowflake" amniotic membrane may help maximize its mechanical and biological benefits and holds promise to be an important adjunctive treatment for surgical wound healing., Competing Interests: Dr S.T. reports receiving book royalties from Spring & Thieme Publishers. The remaining authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Introduction: This prospective study evaluated the effect of immediate functional loading (IFL) of a full-coverage prosthesis on the clinical and radiographic outcome of nonsurgical endodontic therapy (NSET) performed on mandibular molar teeth with pulp necrosis and asymptomatic apical periodontitis., Methods: In 20 subjects, standardized 2-visit NSET was performed in bilateral mandibular first molar teeth (split-mouth model) with a diagnosis of pulp necrosis and asymptomatic apical periodontitis exhibiting a radiographic periapical index (PAI) score ≥3. In each subject, the nonvital bilateral mandibular first molar teeth were randomized to 1 of 2 groups: the IFL group or the functional loading after a time interval of 6 months group. Provisional full-coverage prostheses were provided within 7 days after the completion of endodontic therapy. The cases were followed up clinically and radiographically at 6 and 12 months. Radiographs were assessed for periapical healing based on PAI scores, which were dichotomized as healed (PAI score ≤2) or nonhealed (PAI score ≥3). The data were compared using chi-square and Fisher exact tests., Results: A recall rate of 100% was achieved at the end of 12 months. All teeth in the IFL group and the functional loading after a time interval of 6 months group were clinically asymptomatic. According to an intergroup comparison between the proportion of teeth healed and nonhealed (radiographic), there was a significant difference (P < .05)., Conclusions: IFL of a full-coverage prosthesis in endodontically treated mandibular molar teeth with pulp necrosis and asymptomatic apical periodontitis delayed periapical healing., (Copyright © 2024 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

The Integra Ⓡ Dermal Regeneration Template (DRT) is a bioengineered dermal substitute that is becoming increasingly popular in the field of reconstruction. Its unique properties allow for immediate wound closure while providing a scaffold for tissue regeneration. Currently, it is commonly used to treat burns, ulcers, and complex wounds. In the setting of traumatic periocular tissue loss, only two prior reports have been published on its use for primary reconstruction. We present our institution's experience with a series of four young patients who received primary reconstruction with Integra Ⓡ DRT as a full-thickness skin substitute for their large traumatic periorbital skin defects.