Advances in wound care最新文献

Objective: The objective of this open-label, interventional, prospective clinical study was to evaluate the effectiveness of a multimodal wound matrix (MWM) in moving chronic, nonhealing wounds that had failed prior therapies onto a healing trajectory. The overall response rate was the proportion of subjects who had greater than 40% reduction in size after 4 weeks of treatment. Secondary objectives included the percentage area reduction (PAR) after 4 and 12 weeks, incidence of ulcer closing, and changes in quality of life. Approach: An open-label, interventional, prospective cohort, real-world evidence study was conducted following the STROBE criteria. Criteria included chronic nonhealing wounds of multiple etiologies in subjects with extensive comorbidities. Results were compared with data from the U.S. Wound Registry. Results: A total of 111 subjects entered the screening phase and 64 were treated. Fifty-three wounds were eligible for the dataset that included 18 diabetic foot ulcers, 19 venous leg ulcers, 2 pressure injuries, 1 surgical, 1 lower extremity wound, and 12 unclassified etiologies. The objective response rate was 42%. The 4-week PAR was 34%. The 12-week PAR was 66%. Eighteen wounds closed by week 12. Innovation: MWM is a formulation technology developed to address the major obstacles that prevent healing. Results were evaluated in a patient population with extensive comorbidities that had failed prior treatments and would be generally excluded from controlled trials. Conclusion: The results from this study support the contention that MWM achieves substantial clinical improvement in a complex patient population not enrolled in clinical trials and demonstrates an advancement in wound management.

Significance: Colorectal cancer is currently ranked third in terms of the global cancer incidence. Enterostomy, a common surgical procedure for colorectal cancer treatment, creates a temporary or permanent stoma in the abdominal wall for waste excretion. Cancer itself and the associated treatments, such as chemotherapy and radiation therapy, increase the likelihood of various types of peristomal skin damage. Recent Advances: Recent research has focused on developing more targeted treatment approaches for peristomal moisture-associated skin damage (P-MASD). In addition, studies are investigating the potential of novel wound care products and therapies to enhance healing and reduce the risk of complications. There is also growing interest in understanding the different types except P-MASD during chemoradiotherapy. Different types match the varied treatments. Thus, we aimed to comprehensively review the most prevalent types of peristomal skin damage during chemoradiotherapy and their associated risk factors. Critical Issues: The five prevalent types of peristomal skin damage that occur during chemoradiotherapy are peristomal radiodermatitis, P-MASD, peristomal acneiform rash, peristomal pyoderma gangrenosum, and peristomal abscess/infection/fistula. The risk factors vary depending on the type; however, they include the radiation dose, ileostomy surgery, chemoradiotherapy-associated diarrhea, use of epidermal growth factor receptor inhibitors, inflammatory bowel disease, and unclear factors. Future Directions: This review guides the clinical identification of peristomal skin damage during chemoradiotherapy, laying a solid foundation for developing effective strategies to prevent this condition.

Objective: The mechanisms of structured exercise therapy (SET) in peripheral artery disease (PAD) are not clear. We have developed an SET module for our large animal model of ischemic myopathy. We hypothesized that SET would increase muscle strength and walking distance in this model. The objective was to discover the SET-dependent mechanisms involved in this process. Approach: After induction of unilateral hind limb ischemia, three animals were exposed to standard environmental enrichment (sedentary or SED) and four animals underwent SET thrice weekly for 4 weeks postoperatively. Walking, hind limb pressure indices, and strength testing were performed weekly. Terminal muscle samples were used for skeletal muscle testing. Results: SET animals increased walking distance over time. SET increased muscle strength in both the ischemic and nonischemic limb. When comparing the ischemic SED hind limb muscle with that of ischemic + SET, the SET group has improved respiration and decreased oxidative stress. Markers of cell death and impaired functional regeneration were increased in SED ischemic muscles but returned toward baseline in the SET ischemic muscle. Innovation: This study uses a validated, large animal model of ischemic myopathy similar to that seen in humans with PAD. The effects of exercise on limb function, strength, and skeletal muscle health are reported in this model. Conclusion: SET increases muscle strength and regeneration by increasing endogenous antioxidants and mitochondrial respiration, resulting in favorable muscle health despite ongoing ischemia. This model may assist in preclinical testing of PAD therapies designed to improve muscle health. [Figure: see text].

Significance: Volumetric muscle loss (VML) results in the loss of large amounts of tissue that inhibits muscle regeneration. Existing therapies, such as autologous muscle transfer and physical therapy, are incapable of returning full function and force production to injured muscle. Recent Advances: Skeletal muscle tissue constructs may provide an alternative to existing therapies currently used to treat VML. Unlike autologous muscle transplants, muscle constructs can be cultured in vitro and are not reliant on intact muscle tissue. Skeletal muscle constructs can be generated from small muscle biopsies and could be used to generate skeletal muscle tissue constructs to replace injured tissues. Critical Issues: To serve as effective therapies, muscle constructs must be capable of generating contractile forces that can assist the function of host skeletal muscle. The contractile force of native muscle arises in part as a consequence of the highly aligned, bundled architecture of myofibers. Attempts to induce similar alignment include applications of tension/strain across hydrogels, inducing aligned architectures within scaffolds, casting tissues in straited molds, and 3D printing. While all these methods have demonstrated efficacy toward inducing myofiber alignment, the extent of myofiber alignment, tissue formation, and force production varies. This manusript critically reviews the advantages and limitations of these methods and specifically discusses their ability to impart mechanical and architectural cues to induce alignment within tissue constructs. Future Directions: As tissue-synthesizing techniques continue to improve, muscle constructs must include more cell types than simply myoblasts, such as the addition of neuronal and endothelial cells. Higher-level tissue organization is critical to the success of these constructs. Many of these technologies have yet to be implanted into host tissue to understand engraftment and how they can contribute to traumatic injury, and as such continued collaboration between surgeons and tissue engineers is necessary to ultimately result in clinical translation.

Objective: Volumetric muscle loss (VML) leads to permanent muscle mass and functional impairments. While mesenchymal stromal cells (MSCs) and their secreted factors can aid muscle regeneration, MSCs exhibit limited persistence in injured tissue post-transplantation. Human placental-derived stem cells (hPDSCs), sharing surface markers with MSCs, demonstrate superior regenerative potential due to their fetal origin. Previously, a biosponge (BS) scaffold was shown to augment muscle regeneration post-VML. This study aims to coapply BS therapy and hPDSCs to further enhance muscle recovery following VML. Approach: A VML defect was created by removing ∼20% of the tibialis anterior muscle mass in male Lewis rats. Injured muscles were either left untreated or treated with BS or BS-encapsulated hPDSCs cultured under normoxic or hypoxic conditions. On day 28 postinjury, peak isometric torque was measured, and the muscle was harvested for analysis. Results: BS encapsulated hPDSCs subjected to hypoxic preconditioning persisted in larger quantities and enhanced muscle mass at day 28 postinjury. BS encapsulated hPDSCs cultured under normoxic or hypoxic conditions increased small myofibers (<500 µm²) percentage, MyoD protein expression, and both pro- and anti-inflammatory macrophage marker expression. BS encapsulated hPDSCs also reduced fibrosis and BS remodeling rate. Innovation: This study is the first to examine the therapeutic effects of hPDSCs in a rat VML model. A BS carrier and hypoxic preconditioning were investigated to mitigate low cell survival postimplantation. Conclusion: hPDSCs augment the regenerative effect of BS. Combining hPDSCs and BS emerges as a promising strategy worthy of further investigation.

Objective: Mitigation of local pathological fibrotic tissue deposition is a target area of interest for volumetric muscle loss (VML); nintedanib has shown promise for reduction of fibrosis after VML. Herein, studies investigate how in sequence antifibrotic treatment administered immediately after VML and delayed rehabilitation could improve functional recovery after VML. Approach: Adult male C57BL/6 mice (n = 36) were VML injured or naïve and randomly assigned to nintedanib (6 mg/kg/day) for 2 weeks or were left untreated; in addition, mice were given access to a running wheel beginning at 2 weeks until 8 weeks. Terminally, mice underwent maximal in vivo functional testing in addition to quantification of muscle collagen content and fibrotic and myogenic markers. Results: Daily running distances (p = 0.17) were similar across groups, but weekly averages were greatest in the VML antifibrotic group (p < 0.01). As expected, 2 weeks post-VML, all VML-injured mice had lower maximal torque normalized to body and muscle mass than naïve. By 8 weeks, running alone after VML did not recover function, but mice that received the antifibrotic treatment before running, had greater torque than those untreated (p < 0.01), with functional measurements similar to naïve muscle that ran, indicating improved functional recovery. Innovation: The ability to translate current Food and Drug Administration-approved pharmaceuticals, in a repurposing approach, is critical to mitigate the pathophysiologic consequences of VML in support of functional recovery. However, foundational and translational studies are still needed to understand feasibility and efficacy. Conclusions: Early prevention of fibrotic tissue deposition supports improvements in muscle quality and force chronically after VML injury.

Objective: Volumetric muscle loss results in intramuscular axotomy, denervating muscle distal to the injury and leading to paralysis, denervation, and loss of muscle function. Once the nerve is damaged, paralyzed skeletal muscle will atrophy and accumulate noncontractile connective tissue. The objective of this study was to determine differences in connective tissue, atrophy, and inflammatory signaling between two paralysis models, botulinum toxin (Botox), which blocks acetylcholine transmission while keeping nerves intact, and neurectomy, which eliminates all nerve-to-muscle signaling. Approach: Twenty male Sprague Dawley rats were randomized and received a sciatic-femoral neurectomy (SFN), Botox-induced muscle paralysis of the proximal femur muscles, quadriceps femoris, hamstrings, and calf muscles (BTX), or sham. Muscle force was measured 52 days postsurgery, and samples were collected for histology, protein, and mRNA assays. Results: SFN and BTX decreased twitch and tetanic force, decreased fiber size by twofold, and increased myogenic expression compared with controls. SFN increased the levels of all major extracellular matrix proteins correlating with fibrosis [e.g., laminin, fibronectin, and collagen type(s) I, III, VI]. SFN also increased profibrotic and proinflammatory mRNA compared with BTX and controls. Innovation: SFN and BTX were similar in gross morphology and functional deficiencies. However, SFN exhibited a higher amount of fibrosis in histological sections and immunoblotting. The present study shows evidence that nerve signaling changes NF-κB and TGF-β signaling, warranting future studies to determine the mechanisms involved. Conclusion: These data indicate that nerve signaling may influence fibrogenesis following denervation, but the mechanisms involved may differ as a function of the method of paralysis.

Wound healing is a dynamic process involving multiple cell types and signaling pathways. Dermal sheath cells (DSCs), residing surrounding hair follicles, play a critical role in tissue repair, yet their regulatory mechanisms remain unclear. This study used single-cell proteomics with the Acan^CreER;R26^{LSL-tdTomato-DTR} mouse model to explore DSC function across different healing stages. All animal procedures were conducted in accordance with the Animal Research: Reporting of In Vivo Experiments guidelines. Gene set enrichment analysis (GSEA) and temporal clustering (Mfuzz) were employed to reveal dynamic functional shifts. GSEA identified enriched gene sets related to interferon-gamma response, inflammatory response, ultraviolet response, myogenesis, and xenobiotic metabolism. Temporal clustering revealed eight distinct clusters: clusters associated with the early contracting and proliferative phases were linked to metabolic activation and oxidative stress, while clusters from the later remodeling phase emphasized extracellular matrix remodeling and structural reorganization. The dynamic expression of epithelial-mesenchymal transition-related genes and keratins supported DSCs' dual epithelial and mesenchymal traits. Additionally, keratins, collagens, integrins, and actin proteins emerged as promising markers or signature molecules for DSCs. This study reveals DSCs' dual traits during wound repair, providing a basis for therapies to enhance healing.

Object: The aim of this study was to compare the long-term effects of fractional carbon dioxide (CO₂) laser treatment with traditional therapy on surgical scars by analyzing and comparing observational indicators. Approach: A randomized controlled trial was conducted on 116 patients who received scar treatment in our hospital, of which 58 patients received fractional CO₂ laser treatment, and 58 patients received injection treatment. The outcome measures comprised the Vancouver Scar Scale (VSS) and the Patient and Observer Scar Assessment Scale (POSAS). The observation intervals occur at specific times. Evaluated at 6 months of follow-up, the outcome was blinded, on-site evaluation using the dermatological appearance scale (DAS) and visual analog scale (VAS). Results: Patients in the fractional carbon-dioxide laser (CO₂FL) group rated better than those in the injection group in the POSAS, VSS, DAS, and VAS scores (p < 0.05). The therapeutic efficacy and patients' satisfaction of the research group were superior to those in the control group. Innovation: Scars following surgical procedures can be treated in a variety of methods, but there is no consensus on the best method. CO₂FL has exhibited safety and is more effective than traditional injection treatments for surgical scars. It is a worthwhile approach to consider in clinical treatment. Conclusions: This study demonstrates that CO₂FL achieves more significant long-term results in surgical scars, including improved scar appearance, safety, and patient satisfaction.

Objective: SN514 is a thermolysin-like enzyme under development as a debrider. Preclinical and non-clinical studies supported a first in human healthy volunteer study to predict the need for protection of periwound skin. Approach: Pharmacologic activity testing compared in vitro digestion of collagen, fibrin, and elastin with relevant enzymes. A Yorkshire pig model of burn injury was used to evaluate debridement over 10 days and effects on intact skin. A human 21-day cumulative irritation study using Webril patches taped to the backs of 38 healthy adult volunteers compared four enzyme concentrations (0.10%, 0.20%, 0.40%, and 0.80% w/w) with the hydrogel vehicle, saline (low irritant control), and 0.2% sodium lauryl sulfate (positive irritant control) using randomized placements and blinded evaluation. Results: SN514 showed excellent digestion of fibrin, elastin, and collagen in vitro. Burn wound studies in Yorkshire pigs showed efficient eschar debridement with minimal periwound erythema. Direct treatment on intact porcine skin for 5 days produced no to limited erythema. The preclinical findings of minimal irritation with SN514 were verified by a Phase 1 first-in-human 21-day cumulative skin irritation test. Irritation was observed to increase stepwise by concentration, confirming formulation accuracy. Each enzyme concentration was found to be "possibly mild in use" (Berger and Bowman method). No treatment emergent adverse events were observed during the study. Innovation: A fast-acting enzyme with a favorable irritation profile, prepared as a stable, ready to use hydrogel formulation, overcomes many recognized shortcomings of enzyme debriders. Conclusion: The overall findings support clinical dose range testing for tolerance and preliminary efficacy.