Development of a Method for Clinical Evaluation of Artificial Intelligence-Based Digital Wound Assessment Tools.

Importance: Accurate assessment of wound area and percentage of granulation tissue (PGT) are important for optimizing wound care and healing outcomes. Artificial intelligence (AI)-based wound assessment tools have the potential to improve the accuracy and consistency of wound area and PGT measurement, while improving efficiency of wound care workflows. Objective: To develop a quantitative and qualitative method to evaluate AI-based wound assessment tools compared with expert human assessments. Design, Setting, and Participants: This diagnostic study was performed across 2 independent wound centers using deidentified wound photographs collected for routine care (site 1, 110 photographs taken between May 1 and 31, 2018; site 2, 89 photographs taken between January 1 and December 31, 2019). Digital wound photographs of patients were selected chronologically from the electronic medical records from the general population of patients visiting the wound centers. For inclusion in the study, the complete wound edge and a ruler were required to be visible; circumferential ulcers were specifically excluded. Four wound specialists (2 per site) and an AI-based wound assessment service independently traced wound area and granulation tissue. Main Outcomes and Measures: The quantitative performance of AI tracings was evaluated by statistically comparing error measure distributions between test AI traces and reference human traces (AI vs human) with error distributions between independent traces by 2 humans (human vs human). Quantitative outcomes included statistically significant differences in error measures of false-negative area (FNA), false-positive area (FPA), and absolute relative error (ARE) between AI vs human and human vs human comparisons of wound area and granulation tissue tracings. Six masked attending physician reviewers (3 per site) viewed randomized area tracings for AI and human annotators and qualitatively assessed them. Qualitative outcomes included statistically significant difference in the absolute difference between AI-based PGT measurements and mean reviewer visual PGT estimates compared with PGT estimate variability measures (ie, range, standard deviation) across reviewers. Results: A total of 199 photographs were selected for the study across both sites; mean (SD) patient age was 64 (18) years (range, 17-95 years) and 127 (63.8%) were women. The comparisons of AI vs human with human vs human for FPA and ARE were not statistically significant. AI vs human FNA was slightly elevated compared with human vs human FNA (median [IQR], 7.7% [2.7%-21.2%] vs 5.7% [1.6%-14.9%]; P < .001), indicating that AI traces tended to slightly underestimate the human reference wound boundaries compared with human test traces. Two of 6 reviewers had a statistically higher frequency in agreement that human tracings met the standard area definition, but overall agreement was moderate (352 yes responses of 583 total responses [60.4%] for AI and 793 yes responses of 1166 total responses [68.0%] for human tracings). AI PGT measurements fell in the typical range of variation in interreviewer visual PGT estimates; however, visual PGT estimates varied considerably (mean range, 34.8%; mean SD, 19.6%). Conclusions and Relevance: This study provides a framework for evaluating AI-based digital wound assessment tools that can be extended to automated measurements of other wound features or adapted to evaluate other AI-based digital image diagnostic tools. As AI-based wound assessment tools become more common across wound care settings, it will be important to rigorously validate their performance in helping clinicians obtain accurate wound assessments to guide clinical care.

A Novel Composite Biomaterial Made of Jellyfish and Porcine Collagens Accelerates Dermal Wound Healing by Enhancing Reepithelization and Granulation Tissue Formation in Mice.

Background and Objective: Impaired dermal wound healing represents a major medical issue in today's aging populations. Granulation tissue formation in the dermis and reepithelization of the epidermis are both important and necessary for proper wound healing. Although a number of artificial dermal grafts have been used to treat full-thickness dermal loss in humans, they do not induce reepithelization of the wound, requiring subsequent epithelial transplantation. In the present study, we sought a novel biomaterial that accelerates the wound healing process. Approach: We prepared a composite biomaterial made of jellyfish and porcine collagens and developed a hybrid-type dermal graft that composed of the upper layer film and the lower layer sponge made of this composite biomaterial. Its effect on dermal wound healing was examined using a full-thickness excisional wound model. Structural properties of the dermal graft and histological features of the regenerating skin tissue were characterized by electron microscopic observation and immunohistological examination, respectively. Results: The composite biomaterial film stimulated migration of keratinocytes, leading to prompt reepithelization. The regenerating epithelium consisted of two distinct cell populations: keratin 5-positive basal keratinocytes and more differentiated cells expressing tight junction proteins such as claudin-1 and occludin. At the same time, the sponge made of the composite biomaterial possessed a significantly enlarged intrinsic space and enhanced infiltration of inflammatory cells and fibroblasts, accelerating granulation tissue formation. Innovation: This newly developed composite biomaterial may serve as a dermal graft that accelerates wound healing in various pathological conditions. Conclusion: We have developed a novel dermal graft composed of jellyfish and porcine collagens that remarkably accelerates the wound healing process.

Comparing the Therapeutic Value of Negative Pressure Wound Therapy and Negative Pressure Wound Therapy With Instillation and Dwell Time in Bilateral Leg Ulcers: A Case Report.

INTRODUCTION: Several reports state that negative pressure wound therapy (NPWT) with instillation and dwell time (NPWTi-d) is useful in the management of intractable ulcers. However, reports comparing the effects of NPWT and NPWTi-d in the same patient are lacking. CASE REPORT: A 76-year-old man with intractable skin ulcers on both lateral malleoli presented to an outpatient clinic. Conservative treatment over a 3-month period had not been effective. The authors applied NPWT to the left leg and NPWTi-d to the right leg with fibular osteomyelitis to encourage granulation for 28 days. Thereafter, they covered both ulcers with split-thickness skin grafts. Negative pressure wound therapy was applied to the both legs for 1 week postoperatively. During periods in which NPWT and NPWTi-d were utilized, the patient received intravenous cefazolin sodium (1 g twice daily), lasting 7 days after skin grafting. Epithelization was completed in the NPWTi-d-treated ulcer in about 3 weeks and in the NPWT-treated ulcer in about 8 weeks due to the difficulty in healing his residual ulcers. In terms of the efficacy of granulation and debridement of infected granulation tissue, NPWTi-d demonstrated better results with increments in the washing amount. Also, NPWTi-d proved superior in terms of the survival status of the skin graft, the time until the residual ulcer disappeared, and the removal of latent bacteria. CONCLUSIONS: From this case report, the authors believe NPWTi-d may be more effective in cases with intractable ulcers associated with infection that need better granulation.

Histopathology and Histomorphological Study of Wound Healing Using Clove Extract Nanofibers (Eugenol) Compared to Zinc Oxide Nanofibers on the Skin of Rats.

In order to evaluate the healing effect of eugenol and other nanofibers, 100 male Wistar rats (200&plusmn;10 g) were used with 14-15 weeks of age in this study. All of the male rats were transferred in the standard cages under controlled exposure conditions in a 12:12 h light/dark cycle with a constant temperature about 22&plusmn;2 oC. In addition, the male rats were fed with pellets. Firstly, anesthesia process was performed by 2% xylazine hydrochloride (10mg/Kg/IP) and 10% ketamine hydrochloride (100mg/Kg/IP), and then the rats were placed on the operating table. Then the dorsal surfaces of the rats&rsquo; skin to ileum were scrubbed and prepared as the next step. A circular wound (with a 7 mm diameter) was created by a 7 mm sterile biopsy punch. All 100 rats were divided into four groups (n=25) randomly named as control, nano zinc oxide (ZnO), eugenol nanofibers, and polycaprolactone groups. After that, they were divided into five groups regarding the wound closure rate in days 3, 5, 7, 14, and 21. Then, the wound dressings were placed on the wounds and renewed every 24 h. At the end of days 3, 5, 7, 14, and 21, the relevant tests, such as histopathology, were conducted by removing the tissue volume using a biopsy punch, and then decapitation process was performed on the rats. It was obvious that eugenol nanofiber showed the best granulation tissue by the production of collagen. Further studies are being performed on wound healing by eugenol nanofiber.

Effects of acellular equine amniotic allografts on the healing of experimentally induced full-thickness distal limb wounds in horses.

OBJECTIVE: To characterize the growth factors contained in equine amniotic membrane allograft (eAM; StemWrap scaffold and StemWrap+ injection) and to evaluate the effect of eAM on equine distal limb wound healing. STUDY DESIGN: Prospective experimental controlled study. SAMPLE POPULATION: Eight adult horses. METHODS: Transforming growth factor (TGF)-ß1, vascular endothelial growth factor (VEGF), epidermal growth factor, platelet-derived growth factor-BB, and prostaglandin E2 (PGE2 ) concentrations in StemWrap+ were assessed with enzyme-linked immunosorbent assay. Two full-thickness 6.25-cm2 skin wounds were created on each metacarpus. On one forelimb, one wound was treated with eAM, and the other was left untreated (eAM control). On the contralateral limb, one wound was treated with a silicone dressing, and the other served as negative control. Three-dimensional images were obtained to determine wound circumference and surface area analyses at each bandage change until healed. Excessive granulation tissue was debrided once weekly for 4 weeks. Biopsy samples were taken to evaluate quality of wound healing via histologic and immunohistochemistry assays. RESULTS: StemWrap+ contained moderate concentrations of TGF-ß1 (494.10 pg/mL), VEGF (212.52 pg/mL), and PGE2 (1811.61 pg/mL). Treatment of wounds with eAM did not affect time to healing or histologic quality of the healing compared with other groups but was associated with increased granulation tissue production early in the study, particularly on day 7. CONCLUSION: Application of eAM resulted in increased granulation tissue production while maintaining appropriate healing of experimental wounds. CLINICAL SIGNIFICANCE: Use of eAM is likely most beneficial for substantial wounds in which expedient production of large amounts of granulation tissue is desirable.

Fully Synthetic Bioengineered Nanomedical Scaffold in Chronic Neuropathic Foot Ulcers.

INTRODUCTION: Chronic ulcerations on weightbearing surfaces of the lower extremities are uniquely challenging and can lead to complications such as infection or amputation. OBJECTIVE: This 3-patient case series of 4 chronic wounds of various etiologies outlines the use of a fully synthetic bioengineered nanomedical scaffold that exhibits durability and allows for cell migration and angiogenesis while resisting enzymatic degradation. MATERIALS AND METHODS: The nanomedical scaffold was rehydrated in sterile saline at room temperature for 3 to 5 minutes until translucent and pliable, then it was fenestrated with a scalpel. Following sharp debridement, it was affixed to the ulcer. A nonadherent dressing was applied, followed by applying a moist sterile dressing in a bolster fashion. RESULTS: All 4 ulcers reached the primary endpoints of granulation, as well as decreased wound size, using the nanomedical scaffold. CONCLUSIONS: The nanomedical scaffold successfully reduced the ulcer depths, stimulated granulation tissue while preventing necrosis, and helped the wounds remain infection free. The outcome of this case series suggests a fully synthetic bioengineered nanomedical scaffold can be used as an alternative to human or animal extracellular matrix in chronic, hard-to-heal neuropathic ulcers.

Implantable Nanomedical Scaffold Facilitates Healing of Chronic Lower Extremity Wounds.

BACKGROUND: Chronic, nonhealing wounds are a growing health care problem in the United States, affecting more than 6.5 million patients annually. OBJECTIVE: This retrospective study evaluates the clinical efficacy and utility of an implantable nanomedical scaffold in the treatment of chronic, nonhealing lower extremity wounds in patients with multiple comorbidities. MATERIALS AND METHODS: Data from patients with chronic wounds that had persisted for ≥ 4 weeks and were unresponsive to existing advanced wound care modalities were included in the study. Wounds received the implantable nanomedical scaffold weekly, or as deemed appropriate, for up to 12 weeks based on physician assessment of wound status. RESULTS: A total of 82 wounds were included in this study; wound types consisted of 34 diabetic foot ulcers, 34 venous leg ulcers, and 14 other wounds. Overall, treated wounds demonstrated progressive and sustained wound area reduction over the course of treatment, with 85% achieving complete closure at 12 weeks. CONCLUSIONS: The implantable nanomedical scaffold proved to be an effective alternative to existing wound matrices capable of supporting the natural wound healing process and may provide significant benefits as part of the treatment algorithm for challenging chronic wounds.

Inpatient and Outpatient Wound Treatment Recommendations: Assessing Use of Negative Pressure Wound Therapy Systems or Oxidized Regenerated Cellulose (ORC)/ Collagen/Silver-ORC Dressings.

The increase in wound prevalence means more patients with wounds are being transferred through care settings than ever before. Although the goals of therapy may be the same in both settings, wound care therapies and dressings differ in availability and appropriateness for each setting. Negative pressure wound therapy (NPWT) modalities and oxidized regenerated cellulose (ORC)/collagen (C)/silver-ORC dressings are available in both inpatient and outpatient care settings, but (to-date) lack comprehensive information regarding best practices in transitioning use of these therapies between various care settings. A panel meeting was convened to provide literature- and experience-based recommendations in transitioning wound care patients between various care settings. The use of NPWT with instillation and dwell time was recommended in wounds contaminated with debris and/or infectious materials or heavy exudate. In addition, ORC/C/silver-ORC dressing application was recommended for surface bleeding and for placement into explored areas of undermining to help promote development of granulation tissue. When transitioning a patient from inpatient to outpatient care, overall health, access to services, severity and complexity of the wound, and equipment availability should be taken into consideration. Treatment modalities to bridge the gap during care transition should be used to help maintain continuous care. For outpatient care, NPWT use was recommended for removal of infectious materials and exudate management. The ORC/C/silver-ORC dressings also may be used to help manage exudate and promote granulation tissue development and moist wound healing. In addition, practice challenges and potential solutions for patient adherence, interrupted care during patient transition, and troubleshooting after hours and weekend device alarms were discussed.

Vascular endothelial growth factor receptor 1 (VEGFR1) tyrosine kinase signaling facilitates granulation tissue formation with recruitment of VEGFR1+ cells from bone marrow.

Vascular endothelial growth factor (VEGF)-A facilitates wound healing. VEGF-A binds to VEGF receptor 1 (VEGFR1) and VEGFR2 and induces wound healing through the receptor's tyrosine kinase (TK) domain. During blood flow recovery and lung regeneration, expression of VEGFR1 is elevated. However, the precise mechanism of wound healing, especially granulation formation on VEGFR1, is not well understood. We hypothesized that VEGFR1-TK signaling induces wound healing by promoting granulation tissue formation. A surgical sponge implantation model was made by implanting a sponge disk into dorsal subcutaneous tissue of mice. Granulation formation was estimated from the weight of the sponge and the granulation area from the immunohistochemical analysis of collagen I. The expression of fibroblast markers was estimated from the expression of transforming growth factor-beta (TGF-ß) and cellular fibroblast growth factor-2 (FGF-2) using real-time PCR (polymerase chain reaction) and from the immunohistochemical analysis of S100A4. VEGFR1 TK knockout (TK-/-) mice exhibited suppressed granulation tissue formation compared to that in wild-type (WT) mice. Expression of FGF-2, TGF-ß, and VEGF-A was significantly suppressed in VEGFR1 TK-/- mice, and the accumulation of VEGFR1+ cells in granulation tissue was reduced in VEGFR1 TK-/- mice compared to that in WT mice. The numbers of VEGFR1+ cells and S100A4+ cells derived from bone marrow (BM) were higher in WT mice transplanted with green fluorescent protein (GFP) transgenic WT BM than in VEGFR1 TK-/- mice transplanted with GFP transgenic VEGFR1 TK-/- BM. These results indicated that VEGFR1-TK signaling induced the accumulation of BM-derived VEGFR1+ cells expressing F4/80 and S100A4 and contributed to granulation formation around the surgically implanted sponge area in a mouse model.

Induced Granulation Tissue but not Artificial Dermis Enhances Early Host-Graft Interactions in Full-Thickness Burn Wounds.

BACKGROUND: Cellular grafts used for skin repair require rapid integration with the host tissue to remain viable and especially to nourish the epidermal cells. Here, we evaluated the responses in the split-thickness skin grafts (STSGs) grafted on three differently treated wound beds: directly on excised wound bed (EX), on an artificial dermal template (DT) and on granulation tissue (GT) induced by cellulose sponge. METHODS: In ten burn patients, after excision, a test area was divided into three sections: One transplanted with STSG instantaneously and two sections had a pre-treatment for 2 weeks with either DT or a cellulose sponge inducing granulation tissue formation and thereafter grafted with STSGs. RESULTS: One week after grafting, the STSGs on GT demonstrated most endothelial CD31+ staining, largest average vessel diameters as well as most CD163+ staining of M2-like macrophages and most MIB1+ proliferating epidermal cells, suggesting an active regenerative environment. STSGs on DT had smallest vessel diameters and the least CD163+ macrophages. STSGs on EX had the least CD31+ cells and the least MIB1+ proliferating cells. After 3 months, this reactivity in STSGs had subsided, except increased dermal cell proliferation was observed in STSGs on EX. CONCLUSIONS: Results show that pre-treatment of wound bed and induction of granulation tissue formation can accelerate host-graft interaction by stimulating graft vasculature and inducing cell proliferation.

Evaluation of xenogeneic extracellular matrix fabricated from CuCl2-conditioned mesenchymal stem cell sheets as a bioactive wound dressing material.

The extracellular matrix has drawn considerable interest in tissue engineering not only acts as a bioactive three-dimensional scaffold but also regulates cell behaviors through providing biochemical signals. Extracellular matrix-based biomaterials, mainly derived from xenogeneic tissues, have shown positive outcomes in promoting cutaneous wound healing. However, such extracellular matrices only contain low doses of growth factors, which limit their therapeutic efficiency. Recent reports demonstrated that cell sheets made from mesenchymal stem cell can accelerate wound repair through enhanced re-epithelialization and angiogenesis, but its clinical translation is hindered by several limitations, such as the risk of aberrant immune responses and cost implications. In this study, acellular extracellular matrices were prepared from CuCl2-conditioned mesenchymal stem cell sheets and their in vivo wound healing properties were evaluated in a mouse model of full-thickness skin defect. We found that extracellular matrices derived from CuCl2-conditioned mesenchymal stem cell sheets have a compact surface with thick solid-like cross-sectional structure. Moreover, CuCl2 dramatically enriched the extracellular matrices with collagen I, collagen III, transforming growth factor-ß1, vascular endothelial growth factor, and basic fibroblast growth factor via hypoxia-inducible factor-1α activation. And as a consequence, the resulting extracellular matrices showed markedly improved in vivo wound healing potency through early adipocyte mobilization, enhanced granulation tissues formation, rapid re-epithelialization, and augmented angiogenesis. Therefore, we consider that the extracellular matrix derived from CuCl2-conditioned mesenchymal stem cell sheets has the potential for clinical translation and may lead to a novel strategy for wound management.

Reactive Soft Tissue Preservation in Maxillary Large Bone Defects.

PURPOSE: Granulation tissue containing reactive soft tissue with potential multipotent stem cells can help socket healing following extraction. The aim of this study was to assess bone healing of maxillary large bone defects while maintaining reactive soft tissue. MATERIALS AND METHODS: A total of 32 patients presenting large bone defects were selected for this prospective study. Eight patients (Group A) presented with large bone defects but an intact buccal cortical plate, while 24 patients (Group B) presented with large bone defects lacking a buccal cortical plate. Teeth were extracted, and reactive soft tissue was left in the defects. Bone volume was assessed through cone beam computed tomography (CBCT) both before tooth extraction and at 4 months. A histomorphometric evaluation was performed. RESULTS: CBCT and cylinder bone cores were obtained for histology and histomorphometry analysis. At 4 months after tooth extraction, CBCT showed bone volume preservation and bone formation and no statistically significant difference in bone volume before and after tooth extraction in group A. However, in group B, over the same time period, a statistically significant increase (P < .01) of vertical bone volume was reported. Biopsy specimens showed the presence of vital bone in the defects 4 months later. CONCLUSION: Reactive soft tissue left in large bone defects after tooth extraction may support a significant bone volume gain and vital bone formation.

Hair follicle-containing punch grafts accelerate chronic ulcer healing: A randomized controlled trial.

BACKGROUND: A prominent role of hair follicle-derived cells in epidermal wound closure is now well established but clinical translation of basic research findings is scarce. Although skin punch grafts have been used as a therapeutic intervention to improve healing of chronic leg ulcers, they are normally harvested from nonhairy areas, thus not taking advantage of the reported role of the hair follicle as a wound-healing promoter. OBJECTIVE: We sought to substantiate the role of hair follicles in venous leg ulcer healing by transplanting hair follicle-containing versus nonhairy punch grafts. METHODS: This was a randomized controlled trial with intraindividual comparison of hair follicle scalp grafts and nonhairy skin grafts transplanted in parallel into 2 halves of the same ulcer. RESULTS: Ulcer healing measured as the average percentage reduction 18 weeks postintervention was significantly increased (P = .002) in the hair follicle group with a 75.15% (SD 23.03) ulcer area reduction compared with 33.07% (SD 46.17) in the control group (nonhairy grafts). LIMITATIONS: Sample size was small (n = 12). CONCLUSION: Autologous transplantation of terminal hair follicles by scalp punch grafts induces better healing than punch grafts harvested from nonhairy areas. Hair punch grafting is a minimally invasive surgical procedure that appears to be effective as a therapeutic tool for chronic venous leg ulcers.

Lymphangiogenesis and NOS Localization in Healing Process after Tooth Extraction in Akita Mouse.

Type I diabetes, an autoimmune disease, induces insulin deficiency, which then disrupts vascular endothelial cell function, affecting blood and lymphatic vessels. Nitric oxide (NO) is an immune-induced destructive mediator in type I diabetes, and inhibition of its production promotes arteriosclerosis. In this study, lymphangiogenesis and expression of NO synthase (NOS) during the healing process after tooth extraction were investigated immunohistochemically in control (C57BL) and Akita mice as a diabetes model. Between 1, 4, and 10 days after extraction, expression of NOS, vascular endothelial growth factor-C (VEGF-C), VEGF receptor-3 (VEGFR-3), and von Willebrand factor was strongest during the granulation tissue phase. This suggests that severe inflammation triggers regulation of NOS and these other angiogenic and lymphangiogenic factors. During the callus phase, a few days after extraction, induced osteoblasts were positive for VEGF-C and VEGFR-3 in both the control and Akita mice, suggesting that bone formation is active in this period. Bone formation in the Akita group exceeded that in the controls. Bone tissue formation was disrupted under hyperglycemic conditions, however, suggesting that such activity would be insufficient to produce new bone.

IMPACT OF PREPARATIONS OF FETOPLACENTAL ORIGIN ON THE WOUNDS HEALING.

Possibilities of application of preparations, containing biologically active substances (BAS) of fetoplacental origin, in systemic therapy of the wounds, were analyzed. Comparison of morphological characteristics of the cold wounds while application of placental extract (PE) and cryopreserved serum of the cord blood (CPSCB) was done. The pronounced stimulating impact on the wounds healing due to improvement of microcirculation in tissues, bordering upon the cryodestruction zone, the local immune processes stimulation, аctivation of the granulation tissue and epithelial wound defect formation were noted. Therapeutic effect of CPSCB is more significant than that of PE. The data obtained serve as a background for the BAS of fetoplacental origin application in complex treatment of the wounds.

Cellular and molecular mechanisms of repair in acute and chronic wound healing.

A considerable understanding of the fundamental cellular and molecular mechanisms underpinning healthy acute wound healing has been gleaned from studying various animal models, and we are now unravelling the mechanisms that lead to chronic wounds and pathological healing including fibrosis. A small cut will normally heal in days through tight orchestration of cell migration and appropriate levels of inflammation, innervation and angiogenesis. Major surgeries may take several weeks to heal and leave behind a noticeable scar. At the extreme end, chronic wounds - defined as a barrier defect that has not healed in 3 months - have become a major therapeutic challenge throughout the Western world and will only increase as our populations advance in age, and with the increasing incidence of diabetes, obesity and vascular disorders. Here we describe the clinical problems and how, through better dialogue between basic researchers and clinicians, we may extend our current knowledge to enable the development of novel potential therapeutic treatments.

Experimental study of fat grafting under negative pressure for wounds with exposed bone.

BACKGROUND: The combination of fat grafting and negative pressure (VAC) therapy represents a synergistic interaction of all essential components for wound healing. The aim of this experimental study was to determine whether it could promote healing of wounds with exposed bone. METHODS: Full-thickness wounds with denuded bone in Sprague-Dawley rats were treated with either polyurethane foam dressing, fat grafting alone, polyurethane foam dressing with VAC, or polyurethane foam dressing with VAC combined with a single, or two administrations of fat graft. Wound healing kinetics, tissue growth, cell proliferation (Ki-67) and angiogenesis (platelet endothelial cell adhesion molecule 1 and α-smooth muscle actin) were investigated. Messenger RNA levels related to angiogenesis (vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF)), profibrosis (platelet-derived growth factor A and transforming growth factor ß), adipocyte expression (fatty acid-binding protein (FABP) 4 and peroxisome proliferator activated receptor γ), and extracellular matrix remodelling (collagen I) were measured in wound tissues. RESULTS: Wounds treated by VAC combined with fat grafting were characterized by cell proliferation, neoangiogenesis and maturation of functional blood vessels; they showed accelerated granulation tissue growth over the denuded bone compared with VAC- or foam dressing-treated wounds. Fat grafting alone over denuded bone resulted in complete necrosis. Expression of angiogenesis markers (VEGF and b-FGF) and adipocyte expression factors (FABP-4) was upregulated in wounds treated with VAC combined with fat grafting. CONCLUSION: Fat grafting with VAC therapy may represent a simple but effective clinical solution for a number of complex tissue defects, and warrants testing in clinical models. SURGICAL RELEVANCE: The combination of fat grafting and vacuum therapy represents a synergistic interaction of regenerative cells, hospitable wound matrix and stimulating micromechanical forces. It could accelerate complex wound healing through cell proliferation, neoangiogenesis and maturation of functional blood vessels. The efficacy of a multimodal wound healing approach is established in this experimental model; it could easily be translated into clinical trials of treatment for difficult wounds.

Xenogenic (porcine) acellular dermal matrix promotes growth of granulation tissues in the wound healing of Fournier gangrene.

This article investigates the application values of Xenogenic (porcine) acellular dermal matrix (XADM) in preparation of a Fournier gangrene wound bed. Thirty-six consecutive cases of patients with Fournier gangrene between 2002 and 2012 were enrolled in our department of our hospital. The patients were divided into two groups according to different methods of wound bed preparation after surgical débridement, including the experimental group (17 cases) and the control group (19 cases). The wounds in the experimental group were covered with XADM after surgical wound débridement, whereas the wounds were cleaned with hydrogen peroxide and sodium hypochlorite solution (one time/day) in the control group. The wound bed preparation time and hospital stay were then compared in the two groups. The wound preparation time was 13.64 ± 1.46 days and hospitalization period was 26.06 ± 0.83 days in the experimental XADM group. In the control group, the wound bed preparation time and hospitalization period were 22.37 ± 1.38 and 38.11 ± 5.60 days, respectively. The results showed statistical differences between these two groups. When used in wound débridement after Fournier gangrene, XADM protects interecological organizations, promotes the growth of granulation tissues, and maximally retains function and morphology of the perineum and penis.

Reduced granulation tissue and wound strength in the absence of α11ß1 integrin.

Previous wound healing studies have failed to define a role for either α1ß1 or α2ß1 integrin in fibroblast-mediated wound contraction, suggesting the involvement of another collagen receptor in this process. Our previous work demonstrated that the integrin subunit α11 is highly induced during wound healing both at the mRNA and protein level, prompting us to investigate and dissect the role of the integrin α11ß1 during this process. Therefore, we used mice with a global ablation of either α2 or α11 or both integrin subunits and investigated the repair of excisional wounds. Analyses of wounds demonstrated that α11ß1 deficiency results in reduced granulation tissue formation and impaired wound contraction, independently of the presence of α2ß1. Our combined in vivo and in vitro data further demonstrate that dermal fibroblasts lacking α11ß1 are unable to efficiently convert to myofibroblasts, resulting in scar tissue with compromised tensile strength. Moreover, we suggest that the reduced stability of the scar is a consequence of poor collagen remodeling in α11(-/-) wounds associated with defective transforming growth factor-ß-dependent JNK signaling.