Wound Edge Research Articles

Effectiveness of stepwise progressive ultra-tension-reducing suture method in treatment of high-tension wounds on chest, back, and limbs

To investigate effectiveness of a novel suture method-stepwise progressive ultra-tension-reducing suture method in closing high-tension wounds on the chest, back, and limbs. A retrospective analysis was conducted on 25 patients with high-tension wounds on the chest, back, and limbs who were treated with stepwise progressive ultra-tension-reducing suture method between January 2022 and December 2022. Among the patients, there were 8 males and 17 females, with an average age of 30.5 years (range, 18-56 years). All wounds after scar or tumor resection were located on the chest, back, upper limbs, and lower limbs in 8, 6, 9, and 2 cases, respectively. The size of wounds ranged from 3.5 cm×2.8 cm to 40.0 cm×15.0 cm. All patients were advised to use topical silicone-based treatments postoperatively. The protrusion of the incision, the height of the protrusion, and the duration of the tension reduction effect were observed. The scar formation at the incision site at 6 months after operation was observed, the scar appearance was evaluated by Vancouver Scar Scale (VSS) score, and the scar width was measured. The patient's satisfaction and adverse reactions to incisions were also evaluated. The incisions significantly elevated, with a height of 0.3-2.5 cm, and the tension reducing effect lasted for 8.5-18.0 weeks after operation, with an average of 13.6 weeks. All incisons healed by first intention. One patient experienced transient hyperpigmentation, which resolved spontaneously. Three keloid patients showed localized redness postoperatively, and 2 experienced local recurrence, which improved significantly after treatment with triamcinolone, 5-fluorouracil injections, and laser therapy. All patients were followed up 6.0-13.5 months, with an average of 10.1 months. At 6 months after operation, all patients had linear scars, with VSS scores ranging from 1.0 to 3.5 (mean, 2.0). The width of the scars ranged from 0.5 to 3.0 mm (mean, 1.4 mm). The patients expressed satisfaction with the effectiveness. The stepwise progressive ultra-tension-reducing suture method for high-tension wounds can effectively reduce the tension at the wound edges, providing a prolonged tension-reducing effect and satisfactory effectiveness.

Role of Myofibroblasts in the Repair of Iatrogenic Preterm Membranes Subjected to Mechanical Stimulation.

We examined the role of myofibroblasts in regulating Cx43 and collagen structure in iatrogenic preterm amniotic membrane (AM) defects subjected to mechanical stimulation. Preterm AM specimens were collected from women undergoing planned preterm caesarean section after in utero intervention for correction of spina bifida by open fetal surgery (n=4 patients; preterm delivery at 34+0weeks to 35+0weeks). Control specimens taken 5cm away from the open fetal surgery defect site were compared with wound edge AM. In separate experiments, the effects of mechanical stimulation and co-treatment with Cx43 antisense on matrix and repair proteins were examined. Specimens were immunostained to detect αSMA and Cx43 in myofibroblasts and counterstained with DAPI to quantify nuclei shape. The direction of collagen fibrils in the wound edge region was examined by SHG imaging. Markers for matrix (collagen, elastin, GAG), inflammation (PGE2) and repair (TGFβ1) were examined by RT-qPCR and biochemical assays. In iatrogenic preterm AM specimens, the diameter of the open fetal surgery defect ranged between 3.5 and 7.5cm. At the wound edge of the open fetal surgery defect, αSMA positive myofibroblasts had deformed nuclei and showed abundant Cx43 localized in the cell bodies or formed plaques. In the fibroblast layer, collagen had degenerated in some regions or had polarity near the wound edge. In preterm AM defects, mechanical stimulation and Cx43 antisense increased the levels of collagen and elastin but not GAG or PGE2 release. Mechanical stimulation increased Cx43 and TGFβ1 gene expression. In open fetal surgery defects, myofibroblasts were elongated with collagen fibrils that either degenerated or had polarity. Whilst cells produced substantially higher Cx43 in the fibroblast than in the epithelial layer, they formed plaques, which may prevent migration and delay healing. Mechanical stimulation of preterm AM enhanced matrix repair proteins and the mechanotransduction should be explored to understand how Cx43 contributes to membrane integrity.

Adipose-mesenchymal stem cell-derived extracellular vesicles enhance angiogenesis and skin wound healing via bFGF-mediated VEGF expression.

This study aimed to investigate whether extracellular vesicles (EVs) derived from adipose-derived mesenchymal stem cells (ASCs) promote skin wound healing by delivering basic fibroblast growth factor (bFGF) to enhance vascular endothelial growth factor (VEGF) expression. ASCs were isolated and transfected with either a bFGF knockdown lentivirus (Lv-sh-bFGF) or a control lentivirus (Lv-sh-NC). EVs were extracted from ASCs cultures and characterized by transmission electron microscopy, nanoparticle tracking analysis, and Western blotting for surface markers. EVs were extracted from the conditioned mediums of ASCs and subjected to different treatments. These EVs or control treatments were injected at the wound edges. Wound healing was assessed using histological techniques, including H&E and Masson's trichrome staining to evaluate tissue regeneration, collagen organization, and immunohistochemistry for CD31 to quantify microvessel density. Protein expression of bFGF and VEGF was measured by Western blotting. ASC-derived EVs significantly promoted angiogenesis and improved skin wound healing. EVs encapsulating bFGF enhanced VEGF expression in the wound tissue, while knockdown of bFGF reduced both bFGF and VEGF expression, leading to delayed wound healing. Further knockdown of VEGF partially reversed the pro-angiogenic and wound-healing effects of bFGF-encapsulated EVs. This study demonstrates that ASC-derived EVs promoted skin wound repair by enhancing angiogenesis and accelerating tissue regeneration through the bFGF/VEGF axis. These findings highlight the therapeutic potential of ASCs-derived EVs in improving skin wound healing.

Bactogram: Spatial Analysis of Bacterial Colonisation in Epidermal Wounds.

Skin barrier damage and subsequent development of harmful microbiota contribute to conditions such as wound infections, atopic dermatitis and chronic wounds, which impact millions of people globally and pose a significant economic burden on healthcare systems. Established microbial sampling methods, such as swabs and tissue biopsies, provide limited information on the spatial distribution of bacteria. We here describe a new method that produces a visual map of the distribution of cultivable bacteria, denoted 'Bactogram', across the whole wound and surrounding skin, suitable for image-based quantification. As part of an exploratory endpoint in a clinical trial we applied the Bactogram method to 48 suction blister wounds in 24 healthy volunteers. Bacteria developed in all wounds, predominantly on the skin under the dressing and near wound edges. Two quantification methods, based on visual scoring and image analysis, demonstrated high inter-, and intra-rater agreement and were used to characterise bacterial re-colonisation during epidermal wound healing. We also demonstrated proof of concept that the method can be used with chromogenic agar to enable spatial identification of pathogenic bacterial species, such as Staphylococcus aureus. In conclusion, this study introduces a simple method for sampling bacteria over large areas and generating a bacterial map that can identify spatial variations in bacterial composition and abundance in skin and wound conditions. Trial Registration: ClinicalTrials.gov identifier: NCT05378997.

Tissue nano-transfection of antimicrobial genes drives bacterial biofilm killing in wounds and is potentially mediated by extracellular vesicles

The emergence of bacteria that are resistant to antibiotics is on track to become a major global health crisis. Therefore, there is an urgent need for new treatment options. Here, we studied the implementation of tissue-nanotransfection (TNT) to treat Staphylococcus aureus-infected wounds by delivering gene cargos that boost the levels of naturally produced antimicrobial peptides. The Cathelicidin Antimicrobial Peptide gene (CAMP), which produces the antimicrobial peptide LL-37, was used as model gene cargo. In vitro evaluation showed successful transfection and an increase in the transcription and translation of CAMP-coding plasmid in mouse primary epithelial cells. Moreover, we found that the extracellular vesicles (EVs) derived from the transfected cells (in vitro and in vivo) carried significantly higher concentrations of CAMP transcripts and LL-37 peptide compared to control EVs, possibly mediating the trafficking of the antimicrobial contents to other neighboring cells. The TNT platform was then used in vivo on an excisional wound model in mice to nanotransfect the CAMP-coding plasmid on the edge of infected wounds. After 4 days of daily treatment, we observed a significant decrease in the bacterial load in the CAMP-treated group compared to the sham group. Moreover, histological analysis and bacterial load quantification also revealed that TNT of CAMP on S. aureus-infected wounds was effective in treating biofilm progression by reducing the bacterial load. Lastly, we observed a significant increase in macrophage recruitment to the infected tissue, a robust increase in vascularization, as well as and an increased expression of IL10 and Fli1. Our results demonstrate that TNT-based delivery of gene cargos coding for antimicrobial compounds to the wound is a promising approach for combating biofilm infections in wounds.

Antibacterial carboxymethyl chitosan hydrogel loaded with antioxidant cascade enzymatic system for immunoregulating the diabetic wound microenvironment

Diabetic wound healing faces several complex challenges, such as hypoxia, oxidative stress, and bacterial infections, which severely inhibit the wound-healing process. Herein, a quaternary ammonium salt-crosslinked carboxymethyl chitosan hydrogel (TPC) with excellent antioxidant and antibacterial properties was developed to immunoregulate the diabetic wound microenvironment. The TPC hydrogel was prepared by first mixing carboxymethyl chitosan (CMCS) and protocatechualdehyde (PA), followed by the addition of a quaternary ammonium cross-linker (TSPBA) and a superoxide dismutase (SOD)–catalase (CAT) cascade system. The immobilized SOD and CAT retained their activity, continuously converting endogenous ·O2− and H2O2 to O2 and H2O. PA also provided the TPC hydrogel excellent oxygen and nitrogen radical scavenging capacity. The quaternary ammonium groups in TSPBA significantly enhanced the inherent antibacterial ability of CMCS-based hydrogels. In diabetic wound-healing experiments, this porous and adhesive TPC hydrogel effectively closed wounds and regenerated skin tissue, resulting in shorter wound edges, thicker granulation, and higher collagen deposition levels compared with other groups. The TPC hydrogel also promoted macrophage polarization toward the M2 phenotype, accelerating wound healing by upregulating IL-10 expression, downregulating IL-6 expression, and enhancing angiogenesis. These results demonstrate the great potential of TPC hydrogel as a promising therapeutic dressing for treating diabetic wounds.

Naturally Inspired Tree-Ring Structured Dressing Provides Sustained Wound Tightening and Accelerates Closure.

Mechanically regulated wound dressings require a rational combination of contraction and adhesion functions as well as balancing exudate-induced swelling issues. However, many of the reported dressings face the dilemma of impaired function and impeded wound self-contraction due to fluid-absorbing swelling. In this study, inspired by the tree ring, a core-ring structured hydrogel dressing capable of mechanical modulation is designed, and prepare it using a simple two-step photopolymerization process. The core covers the center of the wound, contracts spontaneously at body temperature to generate a contractile force of 3.4kPa, and resists swelling. Meanwhile, the ring adheres to the normal epidermis around the wound and transfers the contraction stress to the wound edge. The integration of a functionally independent core and ring ultimately achieves effective wound traction and avoids dressing swelling. In murine and porcine skin wound-healing models, this hydrogel with a closely connected core and ring promotes healing by accelerating epidermal closure (50% closure in mouse skin on day 2, 85% closure in pig skin on day 8), collagen deposition, vascular maturation, and extracellular matrix remodeling. These results can guide further research on mechanical force modulation in wound healing, with the potential for clinical translation.

Umbilical cord mesenchymal stem cells combined with autologous platelet-rich plasma for lower extremity venous ulcers: A case report and literature review.

Nonhealing ulcers are difficult to manage because they deviate from the normal wound healing process. Conventional therapy cannot achieve satisfactory therapeutic effects. To verify the effectiveness of combined treatment with human umbilical cord mesenchymal stem cells (hUMSCs) and platelet-rich plasma (PRP) for nonhealing ulcers, we studied a patient with left lower limb venous ulcer (LEVU) treated with combined injection therapy. We present the case of a LEVU patient who has not healed for a long period of time (up to 1 year). LEVU was diagnosed with clinical symptoms. The hUMSCs plus PRP were injected into the wound edge and base (1 µL of cells/cm2 of wound surface), 0.5 mL at each point, with a distance of approximately 1 to 3 cm between points. The injection point was determined according to the extent of wound involvement. Seven days after hUMSC + PRP application, the wound area decreased by nearly 50%. The ulcers had almost completely healed by day 62, and no serious treatment-related toxic side effects were observed. hUMSCs can improve wound healing through re-epithelialization, increased angiogenesis, and granulation tissue formation. PRP has also been suggested to promote wound healing through the secretion of various nutritional factors. The combination of hUMSCs and PRP has a mutually reinforcing effect, which may achieve a 1 + 1 > 2 effect. Therefore, the combination of hUMSCs and PRP may be a safe and effective treatment option for LEVU.

Os efeitos curativos do uso da pele de tilápia para curar queimaduras e feridas

Introdução: A pele de tilápia, um peixe de água doce, está sendo utilizada no tratamento de pacientes com queimaduras graves. Objetivos: O objetivo deste estudo foi identificar as evidências sobre o uso da pele de tilápia na cicatrização de queimaduras. Material e Métodos: A metodologia utilizada foi uma revisão de literatura. A pesquisa foi realizada por meio de busca eletrônica de artigos científicos publicados nos sites Scielo (Scientific Electronic Library Online) e Lilacs (Literatura Latino-Americana em Ciências da Saúde) e Pubmed. Foram utilizadas as terminologias de saúde consultadas nos descritores em Ciências da Saúde (DeCS/BIREME); evidências sobre o uso da pele de tilápia na cicatrização de queimaduras. Discussão: os bons resultados com pele de tilápia, solução salina, hidrofibra com prata e sulfadiazina de prata, porém a pele de tilápia e seus derivados apresentaram melhor delineamento das bordas da ferida, redução do exsudato, redução da formação de crostas, manutenção da umidade local. Isso resultou em tempos de cicatrização mais curtos, menos trocas de curativos e menos dor relacionada às trocas de curativos. Os testes histológicos mostram biocompatibilidade entre a pele humana e a pele de tilápia, sendo que nos testes microbiológicos não foi identificado crescimento bacteriano, e nas análises bioquímicas, a pele de tilápia apresentou maior porcentagem de colágeno tipo I do que o observado na pele humana, e mostrou-se resistente nos testes de tração. Conclusão: Os estudos incluídos nesta revisão mostraram que o uso da pele de tilápia como curativo biológico é eficaz no tratamento de queimaduras, pois adere bem ao leito da ferida, tem boa resistência à tração, não tem antigenicidade e reduz a dor. A assistência à saúde prestada ao paciente queimado é realizada diretamente pela equipe de enfermagem, que realiza todos os curativos e avalia o processo de cicatrização. O uso da pele de tilápia como curativo alternativo para esses pacientes permite que os enfermeiros prestem uma assistência de melhor qualidade e melhorem o conforto do paciente.

Suturing techniques

The act of suturing wounds on the skin has been done for thousands of years. Closing dead space, supporting and strengthening wounds until healing increases their tensile strength, approximating skin edges for an esthetically pleasing and functional result, and minimizing the risks of bleeding and infection remain the primary goals of suture techniques, even though suture materials and techniques have changed. A well-planned closure or flap may have its post-operative appearance jeopardized if the wrong suture technique is used or if the procedure is not performed well. On the other hand, poor surgical skills cannot entirely be made up for by careful suturing. Poor incision placement with respect to relaxed skin tension lines, excessive removal of tissue, or inadequate undermining may limit the surgeon’s options in wound closure and suture placement. Gentle handling of the tissue is also important to optimize wound healing. The choice of suture technique depends on the type and anatomic location of the wound, thickness of the skin, degree of tension, and desired cosmetic result. Proper placement of sutures enhances the precise approximation of the wound edges, which helps minimize and redistribute skin tension. Wound eversion is essential to maximize the likelihood of good epidermal approximation. Eversion is desirable to minimize the risk of scar depression secondary to tissue contraction during healing. Usually, inversion is not desirable, and it probably does not decrease the risk of hypertrophic scarring in an individual with a propensity for hypertrophic scars. To maximize the esthetic and functional outcomes, dead space must be removed, natural anatomic shapes must be restored, and stitch marks must be minimized. This page describes the methods for placing sutures for different kinds of stitches, goes over why certain suture techniques are better than others and goes over the benefits and drawbacks of each suture technique. For the best possible closure of a wound, multiple suture techniques are frequently required. After reading this article, the reader ought to comprehend the basic techniques for inserting each type of suture as well as how and why specific sutures are selected.

Efficacy of Cytoreg in the treatment of diabetic foot disease.

Complications from diabetic foot wounds, including bacterial infection, ulceration and gangrene, are major causes of hospitalisation and are responsible for 85% of amputations in patients with diabetes. Given that orally administered investigational therapeutic Cytoreg (Cytorex de Venezuela SA, Venezuela), a defined aqueous mixture of hydrofluoric, hydrochloric, sulfuric, phosphoric, citric and oxalic acids, has been shown to increase levels of arterial blood oxygen in a Wistar rat model, oral and oral+topical Cytoreg were tested on patients with diabetic foot ulcers (DFUs) under a humanitarian, compassionate-use protocol. All patients received oral Cytoreg (5.0 ml concentrate in fruit juice) for 30 days; half also received weekly wound washing with Cytoreg concentrate in isotonic saline (1:50 volume/volume) (oral+topical group). In addition to standard clinical observations, wounds were monitored against the Saint Elian checklist system for the diabetic foot. A total of 10 patients took part in the study. Complete wound closure was observed in 4/5 patients in the oral+topical group; in the remaining patient, necrotic and fibrin tissues on the wound edges were eliminated. Half (2/4) of the patients receiving oral-only Cytoreg experienced complete wound closure; one patient in this group was removed prematurely because of an unrelated illness and was not replaced. During the study, no significant differences were observed between groups in either the oxygen saturation of the affected tissues or in insulin and glycaemia levels (p<0.05). Significant increases in arterial haemoglobin and arterial oxygen partial pressure (p<0.05) were observed, and significant decreases were measured in the levels of glycosylated haemoglobin, aspartate aminotransferase, glutamic-pyruvic transaminase, creatine and urea (p<0.05). The results of this study justify an expanded clinical study for the treatment of DFUs with Cytoreg.

FOXO3A Plays a Role in Wound Healing by Regulating Fibroblast Mitochondrial Dynamics

The skin plays a protective role against harmful environmental stress such as UV rays. Therefore, the skin is constantly exposed to potential injuries, and wound healing is a vital process for the survival of all higher organisms. Wound healing is dependent on aging and metabolic status at a whole-body level. Because the FOXO family plays a role in aging and metabolism, we investigated the molecular functions of FOXO3A in skin wound healing using FoxO3a-/- mice. We observed that FoxO3a-/- mice showed accelerated skin wound healing. During wound healing, more fibroblasts accumulated at the wound edges and migrated into the wound bed in FoxO3a-/- mice. Moreover, cell migration of dermal fibroblasts isolated from FoxO3a-/- mice was significantly induced. During the invitro cell migration, we observed accelerated mitochondrial fragmentation and decreased oxygen consumption in the mitochondria of FoxO3a-/- fibroblasts. These changes were caused by the upregulation of mitochondrial Rho GTPase 1, which is an essential mediator of microtubule-based mitochondrial motility. Mitochondrial Rho GTPase 1 inhibition significantly attenuated cell migration, mitochondrial fragmentation, and mitochondrial recruitment to the leading edge of the cells. These data indicate that FOXO3A plays a crucial role in wound healing by regulating mitochondrial dynamics.

Optimising wound healing: the role of gelling fibre technology and antimicrobial silver nanoparticles.

Gelling-fibre dressings have been found to be a rapid and effective tool for exudate management. Suprasorb Liquacel Pro is a soft, conformable non-woven dressing made from sodium carboxymethyl cellulose and strengthening cellulose fibres. When it comes into contact with wound exudate or blood, the absorbent dressing forms a gel, creating a moist wound environment. Cell debris and bacteria in the exudate are retained inside the fibre dressing and removed during the dressing change. The high vertical absorption of exudate into the fibre dressing protects the wound environment and the wound edge, thus supporting the healing process. Suprasorb Liquacel Ag has additional antimicrobial abilities with the inclusion of nanosilver technology, shown to be effective in killing bacteria and managing bioburden.

To Sew or Not to Sew: A Case Report

Introduction-Tongue injuries in children vary from slight lacerations to complete amputations. It could be due to fall, self-mutilation, epilepsy, child abuse, or sport injury. The anterior dorsum is the most common site followed by the mid dorsum and anterior ventral part. These injuries may cause dysfunction of tongue, hemorrhage, and disfigurement. Management of injuries of tongue in young children is challenging. There are no established guidelines for managing tongue lacerations. This is a case report of a three-year-old girl with a laceration on the anterolateral part of the tongue with non-approximating wound edges. The laceration extended from the dorsal to the ventral part. The parents were apprehensive about the surgical management of the injury due to the age of their daughter. Hence, healing of the injury with conservative management without suturing was achieved. Conclusion-The management of traumatic injuries of tongue in children is difficult due to their age and cooperation. The pediatrician has to decide whether to heal the tongue by primary or secondary intention. Our decision to allow the healing by secondary intention was successful. The tongue healed without any complications barring a small scar with satisfactory aesthetic and functional outcome. Both the parents and the child were satisfied with the management of the injury.

Analysis of mRNA expression profile in the treatment of diabetic foot ulcer healing by tibial cortex transverse distraction

To investigate mRNA Expression profile and associated signaling pathways in the treatment of diabetic foot ulcer healing by tibial cortex transverse distraction. Tissue samples were collected from the wound edge before and after the surgery. After reference genome transcriptome sequencing and subsequent bioinformatics analysis, the differentially expressed genes and related pathways were explored, and functional analysis of important genes and pathways was conducted. qRT-PCR was used to verify the significantly expressed genes-HLA-DRB1, HLA-DRB5, CXCL5 and IGFL1. There were 2441 significantly up-regulated and 3904 significantly down-regulated genes in the postoperative group. The qRT-PCR results showed the expression of HLA-DRB1, HLA-DRB5 and CXCL5 was consistent with the transcriptional sequencing results. CXCL5 and CXCL6 differentially up-regulated genes are involved in the process of neovascularization, and HLA-DRB1 is involved in the improvement of the degree of diabetic peripheral nerve degeneration. Pathway analysis showed that differential genes were most significantly enriched in Adherens junction, Inflammatory mediator regulation of TRP channels and Wnt signaling pathway. Inflammatory mediator regulation of TRP channels is involved in the improvement of peripheral neurodegeneration, VEGF signaling pathway is involved in the process of neovascularization, and Wnt signaling pathway is involved in the process of bone healing. Significantly up-regulated CXCL5 and CXCL6 and enriched VEGF signaling pathway analyzed are involved in postoperative lower limb neovascularization. The HLA-DRB1 and the enriched Inflammatory mediator regulation of TRP channels may be related to the improvement of postoperative peripheral neurodegeneration. The differentially expressed genes and related pathways can provide objective basis for further mechanism study.

TREATMENT OF TROPHIC COMPLICATIONS IN DECOMPENSATED FORMS OF IMPAIRED ARTERIAL BLOOD CIRCULATION OF THE LOWER EXTREMITIES

Summary. The aim of the study was to study the clinical effectiveness of using the developed method of cryopreservation on wound surfaces using a cryopreservation device. Materials and methods. 87 patients with ulcerative-necrotic defects of the lower legs and feet were selected for the study. The condition for inclusion in the study was Phase I of the wound process. Patients were divided into the main and comparison groups. The main group included 41 patients who had their wounds cleaned according to the proposed method, and the comparison group consisted of 46 patients who underwent surgical treatment. Results. The use of cryodestruction of the surface of trophic ulcers of arterial etiology led to rapid cleaning of necrotic masses, fibrin, a decrease in exudation and pain intensity, and the disappearance of unpleasant odors. The effectiveness of the methods lies in the fact that not only necrotic components of the wound surface, fibrin films, as well as the surface layers of ulcer surface cells are destroyed, that is, phenotypically altered cells of the wound edge and base are removed, leading to a violation of regeneration processes. Conclusions. Debridment methods based on the use of controlled cryodestruction of pathological tissues on the surface of trophic ulcers accelerate the transition of the wound process to phase II by 25% in patients with trophic ulcers with critical ischemia of the lower extremities.

Case Report: Delayed Diagnosis of Leprosy-Related Neuropathic Ulcer, Insights from a Case of Delay to Diagnose across Four Clinical Settings

Background Neuropathy is common in both Diabetes Mellitus (DM) and Leprosy, often resulting in neuropathic ulcers. Leprosy-related neuropathic ulcers are frequently misdiagnosed as DM-related, causing delays in appropriate care. This case report underscores the importance of timely recognition and a better understanding of Leprosy-related neuropathic ulcers to prevent misdiagnosis and improve patient outcomes. Methods The case report adopt the CARE Guidelines and was conducted at the Wound Care Specialist Clinic, Griya Afiat, Makassar, East Indonesia. Data were collected using a Minimum Data Sheet (MDS) to capture demographics, health history, and history of treatments. A head-to-toe assessment focused on the eyes, hands, and feet, with neuropathy, confirmed using the Semmes Weinstein Monofilament test, and angiopathy was assessed by palpating the dorsal pedis and posterior tibialis pulse. Wound care interventions consisted of cleansing, debridement, and dressing. Given the similarities between Leprosy-related neuropathic ulcers and DM-related neuropathic ulcers, the DMIST (depth, maceration, inflammation/infection, size, tissue type of the wound bed, type of wound edge, and tunnelling/undermining) tool was used to evaluate wound healing progress. Results Anamnesis indicated patient has no DM, with normal blood glucose; however, the patient had neuropathic wounds on her feet, asymmetrical eyebrow distribution, and rashes on her hands and calves, with neuropathy confirmed by a monofilament test—initial treatment involved Cadexomer Iodine powder to control bacterial growth and Honey-based gel to promote granulation. Over 62 days, 11 treatments were administered, with an average dressing change every 5.6 days, which improved the DMIST score from 12 to 4 by the end of observation day. Conclusions This case report highlights the significance of distinguishing leprosy-related neuropathic ulcers from those associated with DM to ensure accurate diagnosis and timely treatment. By employing comprehensive assessment tools and targeted wound care interventions, significant improvements in wound healing were achieved, emphasizing the need for greater awareness and clinical vigilance in managing Leprosy-related neuropathic ulcers.

Epidermal Growth Factor Intralesional Delivery in Chronic Wounds: The Pioneer and Standalone Technique for Reversing Wound Chronicity and Promoting Sustainable Healing.

The early expectations about growth factors' (GFs') discovery as an undisputed therapeutic solution for chronic wounds progressively eclipsed when they failed to accelerate acute wound closure and restore the healing trajectory of stagnant ulcers. Critical knowledge about chronic wound biology and GF pharmacology was a conundrum at that time. Diabetes undermines keratinocytes' and fibroblasts' physiology, impairing skin healing abilities. Diabetic ulcers, as other chronic wounds, are characterized by hyperinflammation, unbalanced proteolytic activity, catabolism, and free radical cytotoxicity. This hostile scenario for the chemical stability, integrity, and functionality of GFs led to the conclusion that topical administration may jeopardize GFs' clinical effectiveness. Epidermal growth factor (EGF) has a proximal position in tissues homeostasis by activating survival and mitogenic pathways from embryonic life to adulthood. Seminal experiments disclosed unprecedented pharmacological bounties of parenterally administered EGF. Accordingly, the experience accumulated for more than 20 years of EGF intralesional infiltration of diabetic wound bottoms and edges has translated into sustained healing responses, such as low recurrences and amputation rates. This delivery route, in addition to being safe and tolerated, has shown to restore a variety of circulating biochemical markers ordinarily disturbed in diabetic conditions. EGF infiltration triggers a cascade of local fibroblast reactions, supporting its molecular integrity, prolonged mean residence time, and ultimately eliciting its receptor trafficking and nuclear translocation. The intralesional delivery route seems to warrant that EGF reaches wound fibroblasts' epigenetic core, mitigating the consequences of metabolic memory imprinting.

HHIP's Dynamic Role in Epithelial Wound Healing Reveals a Potential Mechanism of COPD Susceptibility.

A genetic variant near HHIP has been consistently identified as associated with increased risk for Chronic Obstructive Pulmonary Disease (COPD), the third leading cause of death worldwide. However HHIP's role in COPD pathogenesis remains elusive. Canonically, HHIP is a negative regulator of the hedgehog pathway and downstream GLI1 and GLI2 activation. The hedgehog pathway plays an important role in wound healing, specifically in activating transcription factors that drive the epithelial mesenchymal transition (EMT), which in its intermediate state (partial EMT) is necessary for the collective movement of cells closing the wound. Herein, we propose a mechanism to explain HHIP's role in faulty epithelial wound healing, which could contribute to the development of emphysema, a key feature of COPD. Using two different Boolean models compiled from the literature, we show dysfunctional HHIP results in a lack of negative feedback on GLI, triggering a full EMT, where cells become mesenchymal and do not properly close the wound. We validate these Boolean models with experimental evidence gathered from published scientific literature. We also experimentally test if low HHIP expression is associated with EMT at the edge of wounds by using a scratch assay in a human lung epithelial cell line. Finally, we show evidence supporting our hypothesis in bulk and single cell RNA-Seq data from different COPD cohorts. Overall, our analyses suggest that aberrant wound healing due to dysfunctional HHIP, combined with chronic epithelial damage through cigarette smoke exposure, may be a primary cause of COPD-associated emphysema.

3D bioprinting of fish skin-based gelatin methacryloyl (GelMA) bio-ink for use as a potential skin substitute.

Gelatin methacryloyl (GelMA), typically derived from mammalian sources, has recently emerged as an ideal bio-ink for three-dimensional (3D) bioprinting. Herein, we developed a fish skin-based GelMA bio-ink for the fabrication of a 3D GelMA skin substitute with a 3D bioprinter. Several concentrations of methacrylic acid anhydride were used to fabricate GelMA, in which their physical-mechanical properties were assessed. This fish skin-based GelMA bio-ink was loaded with human adipose tissue-derived mesenchymal stromal cells (ASCs) and human platelet lysate (HPL) and then printed to obtain 3D ASCs + HPL-loaded GelMA scaffolds. Cell viability test and a preliminary investigation of its effectiveness in promoting wound closure were evaluated in a critical-sized full thickness skin defect in a rat model. The cell viability results showed that the number of ASCs increased significantly within the 3D GelMA hydrogel scaffold, indicating its biocompatibility property. In vivo results demonstrated that ASCs + HPL-loaded GelMA scaffolds could delay wound contraction, markedly enhanced collagen deposition, and promoted the formation of new blood vessels, especially at the wound edge, compared to the untreated group. Therefore, this newly fish skin-based GelMA bio-ink developed in this study has the potential to be utilized for the printing of 3D GelMA skin substitutes.