Wound Healing Outcomes Research Articles

Enhancing wound healing through innovative technologies: microneedle patches and iontophoresis

IntroductionWound healing is a complex process involving multiple stages, including inflammation, proliferation, and remodeling. Effective wound management strategies are essential for accelerating healing and improving outcomes. The CELLADEEP patch, incorporating iontophoresis therapy and microneedle technology, was evaluated for its potential to enhance the wound healing process.MethodsThis study utilized a full-thickness skin defect model in Sprague-Dawley rats, researchers compared wound healing outcomes between rats treated with the CELLADEEP Patch and those left untreated. Various histological staining techniques were employed to examine and assess the wound healing process, such as H&E, MT and immunofluorescence staining. Furthermore, the anti-inflammatory and proliferative capabilities were further investigated using biochemical assays.ResultsMacroscopic and microscopic analyses revealed that the CELLADEEP patch significantly accelerated wound closure, reduced wound width, and increased epidermal thickness and collagen deposition compared to an untreated group. The CELLADEEP patch decreased nitric oxide and reactive oxygen species levels, as well as pro-inflammatory cytokines IL-6 and TNF-α, indicating effective modulation of the inflammatory response. Immunofluorescence staining showed reduced markers of macrophage activity (CD68, F4/80, MCP-1) in the patch group, suggesting a controlled inflammation process. Increased levels of vimentin, α-SMA, VEGF, collagen I, and TGF-β1 were observed, indicating enhanced fibroblast activity, angiogenesis, and extracellular matrix production.DiscussionThe CELLADEEP patch demonstrated potential in promoting effective wound healing by accelerating wound closure, modulating the inflammatory response, and enhancing tissue proliferation and remodeling. The CELLADEEP patch offers a promising non-invasive treatment option for improving wound healing outcomes.

Outcomes of dermal substitutes in burns and burn scar reconstruction: A systematic review and meta-analysis.

Dermal substitutes have been introduced in burn care to improve wound healing outcomes; however, their use remains limited in standard treatments. This systematic review and meta-analysis aimed to evaluate the outcomes of dermal substitutes in patients with burns and patients requiring burn scar reconstruction and subsequently contribute to optimising the integration of dermal substitutes into clinical practice and reducing the knowledge gap. A comprehensive search across various databases included human studies from peer-reviewed journals on dermal substitutes for deep dermal and full-thickness burns, and scar reconstruction across all ages. Data from comparative trials were extracted, focusing on patient and wound characteristics, treatment specifics, and outcomes related to wound healing and scar quality. Meta-analysis was performed on trials reporting similar post-burn measures, with statistical heterogeneity assessed. Outcomes were presented using mean differences or odds ratios with 95% confidence intervals. A total of 31 comparative trials were included. The overall quality of the studies was considered moderate. The meta-analysis indicated delayed re-epithelialization 4-7 days after treatment with a collagen-elastin matrix compared to split-thickness skin graft in acute burns (-7.30%, p = 0.02). Significant improvement in subjective scar quality was observed with acellular dermal matrix compared to split-thickness skin graft in acute burn wounds 6 months post-operative (-1.95, p <0.01). While acknowledging the initially delayed wound healing, incorporating dermal substitutes into the surgical treatment of burn patients holds promise for enhancing scar quality. However, future research must prioritise outcome measure uniformity, address variations in dermal substitute application, and standardise indications for consistent and effective practices.

Surgeon experience affects perioperative pain in cats undergoing elective ovariohysterectomy: a randomized clinical trial.

This study aimed to compare the outcomes between surgeries performed by either experienced or inexperienced surgeons by assessing intraoperative nociception and perioperative analgesia. 16 healthy, client-owned female cats were randomly allocated into 2 groups of 8: one undergoing surgery by an experienced surgeon (GES group) and the other by inexperienced surgeons (GIS group). Both groups received IM premedication with acepromazine (0.05 mg/kg) and methadone (0.3 mg/kg). After 20 minutes, venipuncture and induction with propofol (dose-response, IV) were performed. Maintenance was achieved with inhaled isoflurane. Intraoperative vital parameters were monitored, and fentanyl (2.5 µg/kg, IV) was administered as rescue analgesia when needed. Postoperatively, pain was assessed with a visual analog scale and the multidimensional pain scale of the Universidade Estadual Paulista in Botucatu; morphine (0.2 mg/kg, IM) was used for rescue analgesia, as necessary. In the GIS group, significant increases in heart rate and systolic blood pressure were noted during surgery, especially during pedicle clamping. Respiratory rate and end-tidal isoflurane levels were higher in the GIS group at specific surgical stages. Survival analysis indicated that the GIS group had a greater need for fentanyl. Postoperative pain scores were generally low, but a higher proportion of GIS cats required rescue analgesia. Surgeon experience influences intraoperative parameters and fentanyl consumption. Inexperienced surgeons contribute to increased postoperative pain and poorer wound healing outcomes in cats undergoing elective ovariohysterectomy. Ovariohysterectomy is a common procedure in veterinary practice, and surgical expertise significantly impacts pain management and recovery. Yet, its effects have been underexplored, potentially compromising animal welfare.

The Negative Pressure Wound Therapy for Flap Salvage

Negative Pressure Wound Therapy (NPWT) effectively manages complex wounds by promoting fluid drainage, stabilizing the wound environment, and reducing bacterial load. It aids in granulation tissue formation and modulation of inflammatory reactions. NPWT is increasingly used in reconstructive surgery, particularly in flap procedures, enhancing wound healing and cosmetic outcomes while reducing flap complications. Despite concerns about flap compromise, clinical trials demonstrate low flap loss rates with NPWT. Strategies like observation windows and implantable Doppler devices help overcome monitoring challenges. However, conclusive evidence regarding NPWT's safety and impact on flap vascularity is limited due to scarce studies. The study involved 40 healthy adult patients, mostly male, with soft tissue defects primarily caused by road traffic accidents. They were split into two groups: NPWT (25 patients) and conventional dressing (15 patients). The NPWT group was further categorized into high pressure (8 patients) and low pressure (17 patients) subgroups. Results showed lower flap edema in NPWT groups compared to controls, but high pressure NPWT led to higher flap ischemia and infection rates. Overall, low pressure NPWT yielded the best clinical and aesthetic outcomes with fewer complications. The study suggests a delayed NPWT approach and low-pressure settings for optimal vascular perfusion in Fasciocutaneous flaps, emphasizing the need for further trials to establish its efficacy and determine ideal pressure settings for different flap types.

TOpClass Class 4 Perineal Crohn's Disease: A Systematic Review and Meta-analysis of Perineal Wound Complication After Proctectomy in Crohn's Patients.

Nonhealing perineal wounds have been reported to be common after proctectomy for Crohn's disease (CD). We performed a systematic review and meta-analysis of perineal wound healing after proctectomy for CD and assessed the risk factors for nonhealing. A comprehensive literature search was conducted in PubMed, Embase, and Scopus databases from 2010 to 2023, and articles reporting perineal wound healing rates after proctectomy for CD were included. Data on study characteristics and proportion of healed wounds, and risk factors, were extracted. Random-effects meta-analysis was performed to estimate the pooled proportion and 95% CIs using the "meta" package in R. Heterogeneity was assessed using the I2 statistic. We identified 501 articles, of which 252 remained after de-duplication. After screening, 4 retrospective cohort studies involving 333 patients were included. Across the 4 studies, the pooled proportion of completely healed perineal wounds at 6 months was 65% (95% CI 52%-80%), and 70% (95% CI 60%-83%) at 12 months. Significant heterogeneity was found between studies (I2 = 86% at 6 months). Three studies examined risk factors for impaired healing after proctectomy. One study identified preoperative perineal sepsis as the only independent factor associated with impaired healing (P = .001) on multivariable analysis. In 1 study, male sex, shorter time from diversion to proctectomy, and higher preoperative C-reactive protein levels were all associated with delayed healing in univariate analysis. Another study found that close rectal dissection was associated with significantly lower healing rates than total mesorectal excision (P = .01). Prior use of tumor necrosis factor inhibitors was not associated with wound healing outcomes. This meta-analysis revealed complete perineal healing in only 70% of patients 12 months after proctectomy for CD. This highlights knowledge gaps, including the identification of modifiable risk factors and methods for preventing or as rescue therapy, such as vacuum-assisted closure and flap reconstruction, for nonhealing perineal wounds after proctectomy for CD. Poor perineal wound healing outcomes are likely related to imperfectly understood underlying inflammatory dysregulation and systemically impaired wound healing in patients with CD.

Comprehensive management of degloving soft tissue injuries of the extremity: A 12-year retrospective study

BackgroundDegloving soft tissue injuries (DSTIs) of the extremities, which are often underestimated in terms of their severity, present significant challenges to reconstructive surgeons. We propose a comprehensive management protocol to standardize the reconstructive approach, aiming for successful treatment of these devastating injuries. MethodsWe retrospectively analyzed data from consecutive patients with extremity DSTIs over a 12-year period. Patients were categorized into three age groups (0–17, 18–65, and >65 years) to highlight the different treatment options based on age. Various surgical techniques were employed depending on the injury pattern. Treatment strategies for each patient were individualized based on age, underlying conditions, and injury type. Wound healing, complications, and functional outcomes were recorded. ResultsOf the hospitalized patients, 20 were lost to follow-up, and 105 were included in the analysis. The mean age at the time of injury was 40 ± 44.9 years, with a mean follow-up of 30.1 ± 12.7 months. Furthermore, 19 % of patients were aged 0–17 years, 61 % were aged 18–65 years, and 20 % were aged >65 years. Treatment plans were personalized based on injury characteristics, with numerous patients being treated with a combination of multiple surgical techniques. Older patients had significantly longer wound healing times and delayed return to activities of daily living compared to the other age groups. Overall, patients were generally satisfied with their outcomes. The total complication rate was 46.7 %, with 79.5 % being categorized as major complications. Each complication was addressed with a tailored treatment plan. ConclusionThe management of DSTIs should be individualized, taking into account the specific characteristics of each injury. Age and medical fitness play crucial roles in determining both the surgical approach and prognosis. An accurate initial evaluation and thorough debridement are essential for optimal outcomes.

Surgical Management of Pediatric Dog Bites: A Systematic Review and Treatment Guideline

IntroductionDog bites are a unique and unusual injury in children, associated with atypical bacterial species, high infection rates, and controversial surgical treatment. Expert recommendations currently guide management and no surgical evidence-based guidelines exist. We conducted a systematic review to answer three management questions: (1) What are the best practices for wound management? (2) In what circumstances should prophylactic antibiotics be administered? (3) In what circumstances should rabies prophylaxis be given? MethodsA structured review was performed using a keyword search querying “pediatric” “dog bite” “management”. Results were reported according to the PRISMA methodology. The quality of nonrandomized studies was evaluated according to Methodological Index for Non-Randomized Studies (MINORS). Qualitative analysis was performed. ResultsA total of 803 studies were identified and 53 studies were included in the final analysis. Current literature suggests that primary closure of bites which are well irrigated and sharply debrided within 8 h of injury, is not associated with increased infection. While dog bites are associated with an overall high rate of infection (6–25 %), routine antibiotic prophylaxis in low-risk wounds does not lower that risk. Postexposure prophylaxis for rabies is indicated for all dog bites where the rabies status of the dog cannot be determined, or the animal cannot be quarantined for 10 days. ConclusionHigh-quality evidence regarding the surgical management of pediatric dog bites is limited. Trial data have demonstrated improved outcomes in wound healing and infection rates with a focus on copious irrigation and diligent wound debridement, although independent validation is needed. Level of EvidenceLevel II – systematic review.

Upper eyelid lymphatic anatomy is associated with blepharoplasty recovery

BackgroundLymphatic vessels support wound recovery and absorb excess fluid. Blepharoplasty involves excess tissue excision, and the present study investigated the relationship between the lymph vessel density of excised tissue and the postoperative course. MethodsForty eyelids from 21 blepharoptosis patients who underwent blepharoplasty were enrolled. Each resected excess tissue sample was divided into four parts by three parasagittal cuts—medial, central, and lateral—and the area percentages occupied by lymphatic vessels and elastic fibers in the cut-exposed inner tissue between skin and muscle were determined by histology. The wound healing process was assessed at 2 weeks and 1, 3, and 6 months postoperatively, by using a visual analogue scale (VAS) for estimating edema and the Vancouver Scar Scale (VSS). ResultsWith increasing age, the area percentage occupied by lymphatic vessels declined significantly (r=-0.581, p<0.001) while an increase in solar elastosis was observed. Percentages of lymphatic vessels were highest at the medial side of the eyelid (p<0.05), and here their relative distribution to the “shallow layer” close to the skin was also highest (p<0.01). Independent of age, the VSS values at 2 weeks and 1 month postoperatively were significantly lower in patients with a higher area percentage of lymphatic vessels (2 weeks: p<0.05; 1 month: p<0.01). ConclusionsIn patients undergoing blepharoplasty, upper eyelid area percentages of lymphatic vessels decreased with advancing age. Higher proportions of lymphatic vessels were associated with improved wound healing outcomes.

Copper Nanoparticle Loaded Electrospun Patches for Infected Wound Treatment: From Development to In-Vivo Application.

This study investigates the development and application of electrospun wound dressings based on polylactic acid (PLA) nanofibers, chitosan, and copper nanoparticles (CuNPs) for the treatment of purulent skin wounds. The materials were evaluated for their structural, antibacterial, and wound healing properties using an animal model. PLA/Ch-CuNPs demonstrated the most significant antibacterial activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, surpassing the other tested materials. The integration of CuNPs into the nanofiber matrices not only enhanced the antimicrobial efficacy but also maintained the structural integrity and biocompatibility of the dressings. In vivo experiments using a rat model showed that PLA/Ch-CuNPs facilitated faster wound healing with reduced exudative and inflammatory responses compared to PLA alone or PLA-CuNPs. Histological and immunohistochemical assessments revealed that the combination of PLA, chitosan, and CuNPs mitigated the inflammatory processes and promoted tissue regeneration more effectively. However, this study identified potential toxicity related to copper ions, emphasizing the need for careful optimization of CuNP concentrations. These findings suggest that PLA/Ch-CuNPs could serve as a potent, cost-effective wound dressing with broad-spectrum antibacterial properties, addressing the challenge of antibiotic-resistant infections and enhancing wound healing outcomes.

Investigating the Influence of Natural Compounds on the Healing Process of Wounds

Advancements in modern medicine have not fully resolved the complexities associated with wound healing, particularly for chronic wounds, such as diabetic ulcers and burn injuries. Effective wound management necessitates not only the regeneration of damaged tissue but also minimizing scar formation. In this context, natural compounds derived from plants have emerged as promising candidates for enhancing wound healing. Ethnobotanical research has demonstrated that various herbal extracts possess properties that could significantly improve wound healing outcomes. This review explores the potential of these natural compounds, focusing on their mechanisms of action, efficacy in clinical and preclinical studies, and the challenges that still need to be addressed. By synthesizing findings from traditional medicinal practices and contemporary scientific research, this review aims to provide a comprehensive understanding of how natural compounds can contribute to more effective wound healing strategies. In this review, widely used and studied plants are discussed, along with their ability to induce wound healing through all the phase and their mechanism of action.

A Comparison of the Efficacy Between Mass Closure and Layer by Layer Closure of Midline Laparotomy and Its Influence on Wound Healing: A Prospective Study

Introduction: The midline laparotomy is the most common approach in surgery which gives access to viscera of the abdomen. Following surgery, the laparotomy wound is sutured by two techniques: mass closure and layer by layer closure. The primary objective of wound closure is to restore the function of the abdominal wall. However the method adopted for incision closure has an influence on the outcomes of wound healing. Our study wants to compare the two suture techniques in terms of efficacy and wound healing. Aims: To compare conventional layer by layer suture technique versus mass closure in terms of efficacy and wound healing in patients with midline laparotomy approach. Methods: A Prospective study with a population size of 94 was performed at the surgery department of Nepalgunj medical college teaching hospital, Nepalgunj, starting from September 2023 to May 2024. A pre-tested questionnaire containing structural, semi-structural, and open-ended questions in printed form was made as a data collection tool. All the people in this study were interviewed after receiving their consent. Patients were followed up for 3 months to rule out any post operative complications. Results: Total 94 patients were studied among which majority of patients were in 30-39 age group. Male outnumbered the females. Incidence of early complications like seroma, wound infection and wound dehiscence was more in layered closure group as compared to mass closure. Average time taken in layered vs. mass closure group is 15 vs 25 mins respectively. Overall wound healing was found more efficacious in mass closure group which is also cost effective than layered closure group. Conclusion: Mass closure technique is less time consuming, along fewer instances of surgical site infection and dehiscence with better overall compliance.

Improved Wound Healing: The Healing Power of Blood Transfusions for Individuals with HIV

Wound healing in individuals with HIV is often compromised due to impaired immune function, chronic inflammation, and common comorbidities like anemia. Blood transfusions, traditionally used to manage anemia, have shown promise in enhancing wound healing through multiple mechanisms. This review explores the role of blood transfusions in improving wound healing for HIV-positive patients, focusing on their impact on oxygen delivery, immune modulation, inflammation reduction, and tissue repair. By restoring adequate hemoglobin levels, blood transfusions can improve oxygenation, support cellular metabolism, and promote collagen synthesis and angiogenesis, all crucial for effective wound healing. In addition to addressing anemia, blood transfusions may offer broader benefits, including the modulation of immune responses and the reduction of systemic inflammation. These effects can create a more favorable environment for wound healing, helping to mitigate prolonged inflammation and tissue damage commonly seen in HIV-positive individuals. Clinical studies and case reports have highlighted significant improvements in wound healing outcomes following transfusion therapy, underscoring its potential as a complementary intervention in HIV care. Keywords: anemia, blood transfusions, HIV, immune response, wound healing,

Enhancing Wound Healing With Sprayable Hydrogel Releasing Multi Metallic Ions: Inspired by the Body's Endogenous Healing Mechanism.

In the pursuit of new wound care products, researchers are exploring methods to improve wound healing through exogenous wound healing products. However, diverging from this conventional approach, this work has developed an endogenous support system for wound healing, drawing inspiration from the body's innate healing mechanisms governed by the sequential release of metal ions by body at wound site to promote different stages of wound healing. This work engineers a multi-ion-releasing sprayable hydrogel system, to mimic this intricate process, representing the next evolutionary step in wound care products. It comprises Alginate (Alg) and Fibrin (Fib) hydrogel infused with Polylactic acid (PLA) polymeric microcarriers encapsulating multi (calcium, copper, and zinc) nanoparticles (Alg-Fib-PLA-nCMB). Developed sprayable Alg-Fib-PLA-nCMB hydrogel show sustained release of beneficial multi metallic ions at wound site, offering a range of advantages including enhanced cellular function, antibacterial properties, and promotion of crucial wound healing processes like cell migration, ROS mitigation, macrophage polarization, collagen deposition, and vascular regeneration. In a comparative study with a commercial product (Midstress spray), developed Alg-Fib-PLA-nCMB hydrogel demonstrates superior wound healing outcomes in a rat model, indicating its potential for next generation wound care product, addressing critical challenges and offering a promising avenue for future advancements in the wound management.

Development and Characterization of a Novel Composite Hydrogel Biomaterial for Improved Mucoperiosteal WoundRepair.

Mucoperiosteal wound healing, as it occurs after pediatric cleft palate surgery, can be challenging due to the limitations of current treatments such as tissue flaps secured with sutures and fibrin glue. In this study, we characterized the in vitro performance of a novel composite hydrogel biomaterial designed to be employed as an in situ wound filler and enhance mucoperiosteal wound healing. We evaluated a range of photopolymerizable formulations containing methacrylated gelatin (GelMA), glycol chitosan, and bioglass microparticles. Our aim was to identify one or more formulations with an appropriate balance of properties against a set of functional requirements that we established for this application. To test the formulations against these criteria, we measured photopolymerization kinetics, mechanical properties, degradation rate, in vitro biocompatibility, and ex vivo tissue adhesion. All formulations polymerized in less than 90 s using violet light. In addition, we found that GelMA-based hydrogels were more adhesive to mucoperiosteal tissue than clinical standard fibrin glue. Inclusion of small amounts of bioglass in the formulation increased mechanical compatibility with mucoperiosteal tissue, enhanced cytoconductivity, and promoted cell proliferation. Taken together, our results support the suitability of these photopolymerized composite hydrogels as in situ mucoperiosteal wound fillers. Overall, this study lays the groundwork for investigating the in vivo, pre-clinical effectiveness of these composite hydrogels in improving mucoperiosteal wound healing outcomes.

Enhanced Wound Healing With β-Chitosan-Zinc Oxide Nanoparticles: Insights From Zebrafish Models.

Wound healing is a complex physiological process essential for the restoration of tissue integrity and function.Novel therapeutic approaches are urgently needed to enhance wound-healing outcomes. Nanotechnology, particularly zinc oxide nanoparticles, has shown promise due to its antimicrobial, anti-inflammatory, and regenerative properties.β-chitosan, derived from squid pens, possesses superior solubility and bioactivity compared toα-chitosan, making it a valuable biomaterial for biomedical applications. Through the integration ofβ-chitosan and zinc oxide nanoparticles, this study seeks to use the complementary properties of both substances to overcome present constraints in wound care treatments. β-chitosan was extracted from squid pens and characterized for its molecular weight, degree of deacetylation, and solubility properties. Further characterization of the synthesized zinc oxide nanoparticles involved Fourier transform infrared spectroscopyto analyze chemical bonding and functional groups, ultraviolet-visible spectroscopy to determine optional properties such as band gap energy, X-ray diffraction spectroscopy to confirm the crystalline phase and calculate crystallite size, and the size was confirmed with the scanning electron microscope. Each technique provided complementary information, ensuring a comprehensive understanding of the synthesized nanoparticles' properties and their potential applications. Adult zebrafish (six to eight months old) were employed as a model organism due to their genetic similarity to humans and regenerative capabilities. Zebrafishwere wounded and divided into treatment and control groups, withβ-chitosan andβ-chitosan-derived zinc nanoparticlestreatments administrated at 50 µg/ml, while control groups received 0.05% phosphate buffer saline. The treatments, conducted in triplicate, enabled a comparative analysis of wound closure activity between β-chitosan-derived zinc nanoparticles' healing effects against standard and baseline treatments. Further, gene expression analysis on Bax, BCl-2, IL-2, IL-6, and tumor necrosis factor-alpha (TNF-a) was done using reverse transcriptase polymerase chain reaction. Characterization studies confirmed the successful synthesis ofβ-chitosan-derived zinc oxide nanoparticles and a crystalline structure corresponding to zinc oxide. Treatment withβ-chitosan-derived zinc oxide nanoparticles significantly accelerated wound closure compared to controls and other treatment groups. Microscopic analysis demonstratedenhanced epithelialization, reduced inflammatory cell infiltration, increased collagen deposition, and improved tissue organization in wounds treatedwithβ-chitosan-derived zinc oxide nanoparticles. Gene expression analysis revealed downregulation of inflammation-causing genes such as BCl-2, IL-2, IL-6, and TNF-a, hence it showed wound-healing activity. The results were statistically significant (p < 0.05). β-chitosan-derived zinc oxide nanoparticles show promising potential as a novel therapeutic strategy for enhancing wound healing. The synergistic effects ofβ-chitosan and zinc oxide nanoparticles address multiple aspects of wound healing, including antimicrobial activity, inflammation modulation, and tissue regeneration. This study highlights the advantages of nanotechnology in wound care and underscores the need for further research to optimize nanoparticle formulations for clinical applications.

Focused Perioperative Nutritional Supplementation Reduces Wound Complications in Patients Undergoing Spinal Fusion Surgery.

Retrospective cohort study. To evaluate intensive postoperative nutritional supplementation on wound healing complications and outcomes after spinal fusion surgery. Poor nutritional status leads to inferior postoperative outcomes by increasing mortality and predisposing patients to infection and wound healing complications. While perioperative nutritional supplementation has shown promise in mitigating these risks, there is a paucity of literature regarding specific nutritional routines in spinal fusion surgery. A retrospective analysis was conducted on patients who underwent spinal fusion surgery between 2019 and 2022. Demographic and nutritional data, including preoperative prealbumin levels (PAB) and postoperative supplemental diet, were examined. Primary endpoints included wound complications, with secondary outcomes assessing Oswestry Disability Index (ODI) and Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Health (PH) scores. Statistical analyses included unpaired t-tests and Chi-squared/Fischer's exact tests with significance set at P<0.05. Patients receiving the supplemental diet (n=229) demonstrated fewer wound complications (7% vs. 21%, P=0.004) and reoperations (3% vs. 11%, P=0.016) compared to those without supplementation (n=56). No significant differences were observed in preoperative or postoperative PROMIS PH or ODI scores. Patients with normal preoperative PAB had more wound complications without the supplemental diet (5% vs. 18%, P=0.025). A similar trend was seen in the patients with low preoperative PAB (12% vs. 26%, P=0.12). Postoperative nutritional supplementation significantly reduces wound complications after spinal fusion surgery in a cost-effective manner. This study underscores the modifiability of certain perioperative risk factors and suggests that nutritional strategies can mitigate potential complications.

Metformin as a Modulator of Autophagy and Hypoxia Responses in the Enhancement of Wound Healing in Diabetic Rats.

The molecular mechanisms underlying delayed wound repair in diabetes involve dysregulation of key cellular processes, including autophagy and hypoxia response pathways. Herein, we investigated the role of topical metformin, an established anti-diabetic drug with potential autophagy-inducing properties, in improving wound healing outcomes under hypoxic conditions. Full-thickness skin wounds were created in streptozotocin-induced diabetic rats, and tissue samples were collected at regular intervals for molecular and histological analysis. The expression levels of autophagy markers LC3B and Beclin-1 were evaluated via immunohistochemistry and qRT-PCR, while the amount of AMP-activated protein kinase (AMPK) and hypoxia-inducible factor-1α (HIF-1α) were determined via ELISA. Our results demonstrated that metformin administration resulted in the upregulation of LC3B and Beclin-1 in the wound bed, suggesting induction of autophagy in response to the treatment. Mechanistically, metformin treatment also led to the increased amount of AMPK, a critical regulator of cellular energy homeostasis, and a subsequent reduction in HIF-1α amount under hypoxic conditions. In conclusion, our findings demonstrate that metformin promotes wound healing in diabetes mellitus by enhancing autophagy through AMPK activation and modulating HIF-1α amount in a hypoxic microenvironment. This study offers a new therapeutic approach by shedding light on the potential benefits of metformin as adjunctive therapy in diabetic wound management.

Exploring the role of dermal sheath cells in wound healing and fibrosis.

Wound healing is a complex, dynamic process involving the coordinated interaction of diverse cell types, growth factors, cytokines, and extracellular matrix components. Despite emerging evidence highlighting their importance, dermal sheath cells remain a largely overlooked aspect of wound healing research. This review explores the multifunctional roles of dermal sheath cells in various phases of wound healing, including modulating inflammation, aiding in proliferation, and contributing to extracellular matrix remodelling. Special attention is devoted to the paracrine effects of dermal sheath cells and their role in fibrosis, highlighting their potential in improving healing outcomes, especially in differentiating between hairy and non-hairy skin sites. By drawing connections between dermal sheath cells activity and wound healing outcomes, this work proposes new insights into the mechanisms of tissue regeneration and repair, marking a step forward in our understanding of wound healing processes.

Photoactivated rose bengal mitigates a fibrotic phenotype and improves cutaneous wound healing in full-thickness injuries.

Healing of deep cutaneous wounds often results in detrimental sequelae, including painful and debilitating scars. Current therapies for full-thickness injuries that target specific phases of wound healing have moderate success; however, full resolution remains incomplete and negative consequences persist if skin homeostasis is not achieved. Photoactivated molecules can modulate cellular responses by generating reactive oxygen species and may provide a novel therapeutic option to improve wound healing. In the current study, we investigated the effects of Rose bengal (RB) dye in a preclinical model of full-thickness cutaneous injury. Monochromatic green light activates RB to generate ROS in the presence of oxygen, subsequently crosslinking collagen fibrils. In in vitro studies, we show that photoactivated RB is well tolerated by epidermal keratinocytes and dermal fibroblasts and can mitigate fibrotic signalling by downregulating collagen production. In a murine model of full-thickness injury, topically-applied and photoactivated RB closed wounds faster than control and vehicle treatments and showed significantly improved wound healing outcomes, including enhanced early granulation, better collagen organisation and increased vascularity in the presence of protracted tissue ROS. These data support an overall improved cutaneous wound healing profile after RB phototherapy and warrant further investigations into this versatile molecule.

Human adipose‐derived multipotent stromal cells enriched with IL‐10 modRNA improve diabetic wound healing: Trigger the macrophage phenotype shift

AbstractDiabetic wounds present a significant challenge in regenerative medicine due to impaired healing, characterized by prolonged inflammation and deficient tissue repair, primarily caused by a skewed pro‐inflammatory macrophage phenotype. This study investigates the therapeutic potential of interleukin‐10 (IL‐10) chemically modified mRNA (modRNA)‐enriched human adipose‐derived multipotent stromal cells (hADSCs) in a well‐established murine model of diabetic wounds. The modRNAs used in this study were chemically modified using N1‐methylpseudouridine‐5′‐triphosphate (m1Ψ) by substituting uridine‐5‐triphosphate. In vitro experiments demonstrated that IL‐10 modRNA‐transfected hADSCs effectively modulated macrophage polarization towards an anti‐inflammatory phenotype. In vivo experiments with a well‐established murine model demonstrated that transplantation of hADSCsmodIL‐10 on postoperative day 5 (POD5) significantly improved wound healing outcomes, including accelerated wound closure, enhanced re‐epithelialization, promoted M2 polarization, improved collagen deposition, and increased neovascularization. This study concludes that IL‐10 modRNA‐enriched hADSCs offer a promising therapeutic approach for diabetic wound healing, with the timing of IL‐10 administration playing a crucial role in its effectiveness. These cells modulate macrophage polarization and promote tissue repair, demonstrating their potential for improving the management of diabetic wounds.