RESUMEN

Introduction: Autologous cell suspension (ACS)-based therapy represents a highly promising approach for burns and chronic wounds. However, existing technologies have not achieved the desired clinical success due to several limitations. To overcome practical and cost-associated obstacles of existing ACS methods, we have established a novel methodology for rapid, enzymatic disaggregation of human skin cells and their isolation using a procedure that requires no specialist laboratory instrumentation and is performed at room temperature. Methods: Cells were isolated using enzymatic disaggregation of split-thickness human skin followed by several filtration steps for isolation of cell populations, and cell viability was determined. Individual population recovery was confirmed in appropriate culture medium types, and the presence of epidermal stem cells (EpSCs) within keratinocyte sub-populations was defined by flow cytometry via detection of CD49 and CD71. Positive mediators of wound healing secreted by ACS-derived cultures established on a collagen-based wound-bed mimic were detected by proteome arrays and quantified by ELISA, and the role of such mediators was determined by cell proliferation assays. The effect of ACS-derived conditioned-medium on myofibroblasts was investigated using an in-vitro model of myofibroblast differentiation via detection of α-SMA using immunoblotting and immunofluorescence microscopy. Results: Our methodology permitted efficient recovery of keratinocytes, fibroblasts and melanocytes, which remained viable upon long-term culture. ACS-derivatives comprised sub-populations with the CD49-high/CD71-low expression profile known to demarcate EpSCs. Via secretion of mitogenic factors and wound healing-enhancing mediators, the ACS secretome accelerated keratinocyte proliferation and markedly curtailed cytodifferentiation of myofibroblasts, the latter being key mediators of fibrosis and scarring. Discussion: The systematic characterisation of the cell types within our ACS isolates provided evidence for their superior cell viability and the presence of EpSCs that are critical drivers of wound healing. We defined the biological properties of ACS-derived keratinocytes, which include ability to secrete positive mediators of wound healing as well as suppression of myofibroblast cytodifferentiation. Thus, our study provides several lines of evidence that the established ACS isolates comprise highly-viable cell populations which can physically support wound healing and possess biological properties that have the potential to enhance not only the speed but also the quality of wound healing.

RESUMEN

Chronic non-healing cutaneous wounds represent a major burden to patients and healthcare providers worldwide, emphasising the continued unmet need for credible and efficacious therapeutic approaches for wound healing. We have recently shown the potential for collagen peptides to promote proliferation and migration during cutaneous wound healing. In the present study, we demonstrate that the application of porcine-derived collagen peptides significantly increases keratinocyte and dermal fibroblast expression of integrin α2ß1 and activation of an extracellular signal-related kinase (ERK)-focal adhesion kinase (FAK) signalling cascade during wound closure in vitro. SiRNA-mediated knockdown of integrin ß1 impaired porcine-derived collagen peptide-induced wound closure and activation of ERK-FAK signalling in keratinocytes but did not impair ERK or FAK signalling in dermal fibroblasts, implying the activation of differing downstream signalling pathways. Studies in ex vivo human 3D skin equivalents subjected to punch biopsy-induced wounding confirmed the ability of porcine-derived collagen peptides to promote wound closure by enhancing re-epithelialisation. Collectively, these data highlight the translational and clinical potential for porcine-derived collagen peptides as a viable therapeutic approach to promote re-epithelialisation of superficial cutaneous wounds.

Asunto(s)

RESUMEN

Tissue-engineered skin constructs, including bi-layered living cellular constructs (BLCC) used in the treatment of chronic wounds, are structurally/functionally complex. While some work has been performed to understand their mechanisms, the totality of how BLCC may function in wound healing remains unknown. To this end, we have developed a delayed wound healing model to test BLCC cellular and molecular mechanisms of action. Diabetes was chemically-induced using alloxan in Yucatan miniature pigs, and full-thickness wounds were generated on their dorsum. These wounds were either allowed to heal by secondary intention alone (control) or treated with a single or multiple treatments of a porcine autologous BLCC. Results indicated a single treatment with porcine BLCC resulted in statistically significant wound healing at day 17, while four treatments resulted in statistically significant healing on days 10, 13, and 17 compared to control. Statistically accelerated wound closure was driven by re-epithelialisation rather than contraction or granulation. This porcine diabetic model and the use of a porcine BLCC allowed evaluation of healing responses in vivo without the complications typically seen with either xenogenic responses of human/animal systems or the use of immune compromised animals, expanding the knowledge base around how BLCC may impact chronic wounds.

Asunto(s)

RESUMEN

A key event in wound healing is re-epithelialisation, which is mainly regulated via paracrine signalling of cytokines, chemokines, and growth factors secreted by fibroblasts. Fibroblast-secreted factors can be collected from the used culture medium, known as dermal fibroblast conditioned medium (DFCM). The goal of this study was to optimise the culture condition to acquire DFCM and evaluate its effect on keratinocyte attachment, proliferation, migration, and differentiation. Confluent fibroblasts were cultured with serum-free keratinocyte-specific (DFCM-KM) and fibroblast-specific (DFCM-FM) medium at different incubation times (Days 1, 2, and 3). DFCM collected after 3 days of incubation (DFCM-KM-3 and DFCM-FM-3) contained a higher protein concentration compared to other days. Supplementation of DFCM-KM-3 enhanced keratinocyte attachment, while DFCM-FM-3 significantly increased the keratinocyte wound-healing rate, with an increment of keratinocyte area and collective cell migration, which was distinctly different from DFCM-KM-3 or control medium. Further analysis confirmed that the presence of calcium at higher concentrations in DFCM-FM facilitated the changes. The confluent dermal fibroblasts after 3 days of incubation with serum-free culture medium produced higher proteins in DFCM, resulting in enhanced in vitro re-epithelialisation. These results suggest that the delivery of DFCM could be a potential treatment strategy for wound healing.

RESUMEN

AIM: The aim of this review is to identify and summarise the key in vitro evidence available to support the use of HydroTac (HRWD-2) to address specific aspects associated with the treatment of both acute and hard-to-heal wounds. BACKGROUND: The provision of a moist wound healing environment to support optimal wound healing has been a basic tenet in wound care since the pioneering work on the benefits of occlusion to support wound healing. Modern wound dressings have adopted the benefits of moist healing through their innovative development. HRWD-2 has been shown in clinical studies to enable and support good healing outcomes and the in vitro evidence in support of this dressing is presented in this article. METHOD: An online literature search (supplemented with a manual search of resources not available online) was conducted to identify articles and studies describing in vitro evidence in support of HRWD-2 in aspects important for promoting a healing response in the clinical environment. RESULTS: In vitro studies showed that HRWD-2 contributes to balancing moisture levels and enhances the availability of growth factors known to be important for re-epithelialisation. Pre-clinical studies indicate that HRWD-2 enhances wound re-epithelialisation. Together these results suggest that HRWD-2 promotes a moist healing environment leading to the dressing supporting re-epithelialisation. In vitro data indicating an intrinsic lower in vitro adherence of HRWD-2 likely translate clinically to the benefits of an atraumatic wound dressing, including reduced pain (specifically at dressing change). CONCLUSION: The in vitro evidence presented in this review supports the successful clinical results reported for HRWD-2 in terms of fluid management, wound healing and pain reduction at dressing change.

Asunto(s)

RESUMEN

Galectins are a family of proteins with at least one carbohydrate-recognition domain. Galectins are present in various tissues and organs and participate in different physiological and pathological molecular reactions in vivo. Wound healing is the basic process of traumatic disease recovery. Wound healing involves three overlapping stages: inflammation, proliferation, and remodelling. Furthermore, a comparison of wound healing with the tumour microenvironment revealed that galectin plays a key role in the wound healing process. The current review describes the role of galectin in inflammation, angiogenesis, re-epithelialisation, and fibrous scar formation and evaluates its potential as a therapeutic drug for wounds.

Asunto(s)

RESUMEN

This narrative clinical review summarises the key evidence in support for the use of a hydro-responsive wound dressing, HydroTac (HRWD-2, PAUL HARTMANN AG, Germany) to address key aspects associated with the treatment of both acute and hard-to-heal wounds. This review demonstrates how HRWD-2 can be used in general to address the challenges presented by a wide range of wound types and skin injuries. It highlights the ability of HRWD-2 to regulate an optimal moist wound environment that promotes wound progression and healing. Key aspects covered in this review include the dressing's ability to: promote certain phases of the wound healing response (for example, re-epithelialisation) address the concepts and needs for wound progression as set out in the TIME wound management framework provide an optimal hydration level reduce tissue trauma and pain at dressing change.

Asunto(s)

RESUMEN

AIMS: To determine the effects of oestrogen or oestrogen deprivation on vaginal wound healing. Impaired wound healing following prolapse surgery may increase the risk of recurrent prolapse in the future. Vaginal oestrogen therapy may improve wound healing, hereby possibly improving surgical outcomes. METHODS: A systematic search of OVID MEDLINE, OVID Embase, and Web of Science was conducted up to January 28, 2020. We included original studies comparing wound healing-related outcomes of oestrogen exposed subjects (female animals and women) to hypo-oestrogenic subjects after vaginal surgery. Data on wound healing-related outcome measures were extracted. For each individual comparison, the standardised mean difference (Hedges' g; SMD) and 95% confidence interval (CI) were calculated. RESULTS: Of the 1474 studies reviewed, 14 studies were included for review, and 11 provided data for meta-analysis. Oestrogen improves neovascularisation (SMD: 1.13, 95% CI: 0.67-1.60), microscopic wound closure (SMD: 0.98, 95% CI: 0.66-1.29), collagen synthesis (SMD: 1.08, 95% CI: 0.42-1.74), and tissue strength (SMD: 1.26, 95% CI: 0.53-1.99) in animals. Oestrogen increases granulation (SMD: 1.67, 95% CI: 0.54-2.79) and accelerates macroscopic wound closure (SMD: 1.82, 95% CI: 1.22-2.42) in women and animals. Oestrogen decreases the inflammatory response (SMD: -0.58, 95% CI: -1.14 to -0.02) in women and animals and reduces levels of transforming growth factor (TGF)-ß1 (SMD: -1.68, 95% CI: -2.52 to -0.83) in animals. All results were statistically significant. CONCLUSIONS: Oestrogen therapy has a positive effect on vaginal wound healing. Future studies should determine whether oestrogen therapy has the potential to improve surgical outcomes.

Asunto(s)

RESUMEN

Chronic wounds are a challenging medical entity for patients, medical professionals and healthcare systems. Frequently, patients present themselves to wound specialists after months or even years of unsuccessful treatment. Recent developments have resulted in a multitude of different advanced wound dressings created to treat complex, chronic wounds, one of which is the polylactide dressing Suprathel. This study aimed at investigating the healing potential of Suprathel in chronic wounds and differentiating between old and "young", diabetic and non-diabetic chronic wounds. A prospective, multicentric, non-controlled intervention study was conducted, treating patients with chronic lower leg ulcers (>3 months) with Suprathel and assessing them weekly. Afterwards, a retrospective analysis was performed analysing the wound size initially, after 4 and after 8 weeks of treatment. Furthermore, a differentiation between diabetic and non-diabetic, and chronic wounds older and younger than 12 months, was assessed. A significant reduction in wound size was observed in the study population after 8 weeks of treatment. The effect size in the diabetic wound and the old chronic wound group even reached more than one, with the other groups still showing a large effect of the intervention. This study shows that Suprathel is a valuable tool in the armamentarium of a wound specialist. Not only could we show a positive effect on chronic wounds, we could even demonstrate a significant wound size reduction in chronic wounds of old and young, as well as diabetic wounds, with the treatment of older chronic and diabetic wounds yielding an even larger effect size. Further randomised, controlled studies are necessary to show the full potential of advanced wound dressing materials in large patient cohorts.

Asunto(s)

RESUMEN

Among the available dressings for partial-thickness burn wound treatment, SUPRATHEL has shown good usability and effectiveness for wound healing and patient comfort and has been used in many burn centres in the last decade. Recently, bacterial nanocellulose (BNC) has become popular for the treatment of wounds, and many studies have demonstrated its efficacy. epicitehydro , consisting of BNC and 95% water, is a promising product and has recently been introduced in numerous burn centres. To date, no studies including direct comparisons to existing products like SUPRATHEL have been conducted. Therefore, we aimed to compare epicitehydro to SUPRATHEL in the treatment of partial-thickness burns. Twenty patients with partial-thickness burns affecting more than 0.5% of their total body surface area (TBSA) were enrolled in this prospective, unicentric, open, comparative, intra-individual clinical study. After debridement, the wounds were divided into two areas: one was treated with SUPRATHEL and the other with epicitehydro . Wound healing, infection, bleeding, exudation, dressing changes, and pain were documented. The quality of the scar tissue was assessed subjectively using the Patient and Observer Scar Scale. Wound healing in patients with a mean TBSA of 9.2% took 15 to 16 days for both treatments without dressing changes. All wounds showed minimal exudation, and patients reported decreased pain with the only significant difference between the two dressings on day 1. No infection or bleeding occurred in any of the wounds. Regarding scar evaluation, SUPRATHEL and epicitehydro did not differ significantly. Both wound dressings were easy to use, were highly flexible, created a safe healing environment, had similar effects on pain reduction, and showed good cosmetic and functional results without necessary dressing changes. Therefore, epicitehydro can be used as an alternative to SUPRATHEL for the treatment of partial-thickness burn wounds.

Asunto(s)

RESUMEN

The initial care of burn wounds and choice of dressing are pivotal to optimally support the healing process. To ensure fast re-epithelialisation within 10-14 days and prevent complications, an optimal healing environment is essential. An innovative dressing based on nanocellulose was used for the treatment of burns in children. Children (0-16 years) with clean, partial-thickness burn wounds, 1 to 10% of the total body surface area were included. Complete re-epithelialisation was achieved within 7-17 days, with 13 patients showing re-epithelialised >95% by day 10. Satisfying results concerning time to re-epithelialisation and material handling were obtained. The possibility to leave the dressing on the wounds for 7 days showed a positive effect in the treatment of children, for whom every hospital visit may cause massive stress reactions. The nanocellulose-based dressing is a promising tool in conservative treatment of burns. Reducing the frequency of dressing changes supports a fast and undisturbed recovery; moreover, the dressing provides an optimal moist healing environment. The time to re-epithelialisation is comparable to frequently used materials, and cost reduction effect can be achieved without loss of quality. Possible pain and distress levels are kept to a minimum; therefore, flexibility and compliance of the patients and their parents are enhanced.

Asunto(s)

RESUMEN

This study examined the changes in haematological and biochemical variables in response to gastric mucosa injury in male Wistar rats divided into four groups according to their ages (3, 6, 12, and 18 months). 0.2 ml of acetic acid was injected intraluminal into the stomach glandular portion of each rat for 45 seconds under anaesthesia. Collection of blood and stomach samples occurred on days 3, 7, 14 and 21 post-induction of gastric ulcer. The results obtained from this study showed 100 % area of gastric mucosa healed in 3-month old rats, 91.72 %, 68.52 % and 62.81 % area of mucosa treated in 6, 12 and 18-month old rats respectively on day 21 post-induction of gastric ulcer. Increased circulation of blood cells in younger rats occurred, neutrophil-lymphocyte ratio (NLR) was decreased in younger rats (3 and 6 months) significantly (p < 0.05) when compared to older rats (12 and 18 months). Lipid peroxidation and glutathione (GSH) levels were elevated in older rats (12 and 18 months) significantly (p < 0.05) when compared to younger rats (3 and 6 months). In comparison, superoxide dismutase (SOD) and catalase levels were decreased in older rats (12 and 18 months) significantly (p < 0.05) when compared to younger rats (3 and 6 months). Histological evaluation showed evidence of early healing with re-epithelialisation and angiogenesis in younger rats, but older rats showed delayed healing. The study showed that the slower rate of healing of gastric ulcer with advancing age in rats might be due to reducing circulating blood cells and anti-inflammatory activities during healing via a lipid peroxidation-dependent mechanism.

RESUMEN

BACKGROUND: Wound infections result in considerable morbidity, mortality and healthcare costs. Antibiotic resistance has complicated wound healing, and new, non-antibiotic-based treatment methods are being developed. AIMS: To evaluate evidence on the safety, efficacy and real-world effectiveness of electroceutical devices (ECDs) that provide continuous electrical stimulation to wounds. METHOD: A systematic search was conducted to identify primary studies published between 2009 and 2019 that described therapeutic wound treatment using portable ECDs. Studies were included if the ECD delivered continuous electrical current directly to the wound area for the duration of treatment. RESULTS: Of 171 citations identified in the search, 13 articles met the inclusion criteria and were analysed. Nine studies evaluated dressings embedded with zinc and silver particles that generated electricity electrochemically, and four evaluated electrode-based units with external batteries. ECDs were effective in healing complex, hard-to-heal wounds that had not responded to other treatments. Four studies showed that ECDs led to complete closure of wounds without complications, and in some cases healed wounds faster than standard of care (SOC). One study found that ECDs resulted in higher ratings by both patients and surgeons than SOC for the progression of wound healing and scar appearance. Additionally, three studies found ECD treatment was less expensive than SOC, due to patients requiring fewer dressing changes or nurse visits. CONCLUSION: ECDs appeared to be a safe, effective and cost-effective method for treating severe, complex and challenging wounds, including hard-to-heal wounds, surgical incisions and skin graft donor sites.

Asunto(s)

RESUMEN

The mechanism underlying the effect of bioelectric field on wound healing in vivo has not been previously investigated. Here, we aimed to investigate the effects of an applied electric field (EF) on epidermal cell migration during wound healing. Using a Bama miniature pig wound model, we applied a power-up device (negative electrode in the wound centre and positive electrode around the wound) with pulsed electrical power, to apply a continuous, stable, and tolerable EF to the wound and provide directional signals for keratinocyte migration towards the wound centre. An EF of 100 mV/mm applied in the same direction as the bioelectric field accelerated wound healing. The keratinocytes exhibited regular and similar shapes, uniform arrangement, and an organised migration pattern. In contrast, 100 mV/mm applied countercurrent to the bioelectric field, delayed wound healing and hindered the keratinocyte migration towards the wound centre. Further, the cells were disorganised, misshapen, irregular, and disoriented. Via the application of a directional stable EF, this study morphologically identified the relationships among wound EF, keratinocyte migration, and wound healing and established theoretical and empirical foundations for the clinical application of bioelectric fields.

Asunto(s)

RESUMEN

Treating chronic skin wounds in patients with diabetes, bed sores, or stasis dermatitis is typically a time-consuming and costly process, and the outcome is not always promising. Concentrated growth factor (CGF) obtained from the autologous venous blood of patients via fractional centrifugation is employed for producing a CGF gel or membrane that can be applied to expedite self-regeneration of skin wounds. In this case report, we presented the results from 18 patients with chronic skin wounds treated with a CGF gel or membrane produced from autologous venous blood. Noticeable granulation tissue and regenerated epidermal coverage were observed in 16 patients who received CGF treatment over various time courses, thereby demonstrating the significant therapeutic effects of CGF treatment in overall wound healing. The other two patients with stasis ulcers in their calves failed to respond to the treatment because of the comorbidity of iliac vein thrombosis. In addition, by culturing HaCaT keratinocytes using CGF membrane as the foundation, we observed that HaCaT cells attached to the CGF membrane migrated and proliferated to form an epithelium-like structure. Comprehensively, the clinical results infer that CGF gel can expedite the regeneration of the soft tissue at the wound, whereas CGF membrane may facilitate its marginal re-epithelialisation. The combination of the two can promote autologous regeneration of both deep and superficial wounds effectively and safely.

Asunto(s)

RESUMEN

BACKGROUND: Mixed partial thickness burns are the most common depth of burn injury managed at a large Australian paediatric hospital specialty burns unit. Prolonged time until re-epithelialisation is associated with increased burn depth and scar formation. Whilst current wound management approaches have benefits such as anti-microbial cover, these are not without inherent limitations including multiple dressing changes. The Biobrane® RECELL® Autologous skin Cell suspension and Silver dressings (BRACS) trial aims to identify the most effective wound management approach for mixed partial thickness injuries in children. METHODS: All children presenting with an acute burn injury to the study site will be screened for eligibility. This is a single-centre, three-arm, parallel group, randomised trial. Children younger than 16 years, with burns ≥ 5% total body surface area involving any anatomical location, up to 48 h after the burn injury, and of a superficial partial to mid-dermal depth, will be included. A sample size of 84 participants will be randomised to standard silver dressing or a Regenerative Epithelial Suspension (RES™) with Biobrane® or Biobrane® alone. The first dressing will be applied under general anaesthesia and subsequent dressings will be changed every 3 to 5 days until the wound is ≥ 95% re-epithelialised, with re-epithelialisation time the primary outcome. Secondary outcomes of acute pain, acute itch, scar severity, health-related quality of life, treatment satisfaction, dressing application ease and healthcare resource use will be assessed at each dressing change and 3, 6 and 12 months post-burn injury. DISCUSSION: The findings of this study can potentially change the wound management approach for superficial partial to mid-dermal burns in children locally and worldwide. TRIAL REGISTRATION: The Australian New Zealand Clinical Trials Registry (ACTRN12618000245291) approved prospective registration on 15 February 2018. Registration details can be viewed at https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374272&isReview=true.

RESUMEN

INTRODUCTION: This study was carried out to compare the efficacy of silver nanoparticle gel (SG), nanosilver foam (SF) and collagen (C) dressings in partial thickness burn wounds. METHODS: This was a single-center, prospective cohort study carried out over a period of 1 year on patients with 15-40% partial thickness thermal burns ≤48 h. Each patient received all three dressings (silver-nanoparticle gel, nanosilver foam, collagen) simultaneously at 3 randomly selected areas which were comparable in terms of burn depth and surface area. Efficacy of the dressings was assessed in terms of healing rates, time taken and ease of application, pain at dressing change, cost, wound-swab culture and scar quality (at 3 months). RESULTS: A total of 20 patients were included. In SF group, number of patients with 60%-80% re-epithelialization on day10 (SG: 10/20; C: 10/20; SF: 16/20; p = 0.042) and complete healing on day14 (SF: 11/20, C: 6/20, SG: 4/20; p = 0.032) was significantly higher. The time for dressing change was similar at admission (p = 0.918) and day 10 (p = 0.163), although majority of the patients in SF group needed less than 10 min. The time taken (<10 min) was significantly lower in SF group by 14th day (SF: 18/20 C: 6/20 SG: 6/20; p < 0.001). The ease of application rated by clinicians as "extremely easy" was significantly better in SF group (SG: 78%, C: 80%, SF: 95%; p = 0.011). There was a significantly faster decrease in pain scores in SF group by 5th day (VAS score SF: 6, C: 8; SG: 8; p = 0.038), however, pain scores were comparable at 2 weeks. The scar quality (p = 0.82), cost (p = 0.09) and infection rates (SG: 7/20; C: 4/20; SF: 3/20; p = 0.05) were comparable. The need for skin-graft cover was lower in SF group (SG: 5/20; C: 3/20; SF: 1/20). CONCLUSION: Nanosilver-foam dressings were found to be more efficacious for re-epithelialization, healing, ease of application, tolerance when compared to silver nanoparticle gel and collagen dressings in partial-thickness burns. All were found to be safe.

Asunto(s)

RESUMEN

Epithelial fusion establishes continuity between the separated flanks of epithelial sheets. Despite its importance in creating resilient barriers, the mechanisms that ensure stable continuity and preserve morphological and molecular symmetry upon fusion remain unclear. Using the segmented embryonic epidermis whose flanks fuse during Drosophila dorsal closure, we demonstrate that epidermal flanks modulate cell numbers and geometry of their fusing fronts to achieve fusion fidelity. While fusing flanks become more matched for both parameters before fusion, differences persisting at fusion are corrected by modulating fusing front width within each segment to ensure alignment of segment boundaries. We show that fusing cell interfaces are remodelled from en-face contacts at fusion to an interlocking arrangement after fusion, and demonstrate that changes in interface length and geometry are dependent on the spatiotemporal regulation of cytoskeletal tension and Bazooka/Par3. Our work uncovers genetically constrained and mechanically triggered adaptive mechanisms contributing to fusion fidelity and epithelial continuity.

Asunto(s)

RESUMEN

The combination of an aging population and an increasing prevalence of diseases associated with impaired-wound healing, including obesity, peripheral vascular disease and diabetes, is likely to result in a dramatic increase in the incidence and prevalence of chronic skin wounds. Indeed, systemic reviews are now not only trying to establish both the prevalence and the often under-estimated socio-economic costs of chronic skin wounds, but most importantly are addressing the impact that chronic wounds have on quality of life. Given the clear need for novel approaches to the management of chronic skin ulceration, ideally developed and tested in the human system in a manner that can be rapidly translated into clinical practice, we examined the effects of multipotent primary human nestin+ progenitor cells on human wound healing in an ex vivo model. Human sweat gland-derived nestin+ cells demonstrated the capacity to significantly promote two key wound healing parameters, i.e., both reepithelialisation and angiogenesis in experimentally wounded, organ-cultured human skin. The current data further support the use of full-thickness human skin wound-healing models ex vivo to pre-clinically test wound healing-promoting candidate agents. Whilst larger studies are required to substantiate a firm "proof-of-concept," our preliminary studies encourage further efforts to systemically determine the potential of cell-based regenerative medicine strategies in general, and the use of skin appendage-associated human nestin+ cells in particular, as novel treatment strategies for chronic skin ulceration.

Asunto(s)

RESUMEN

Wound healing is a complex multistep process which is temporally and spatially controlled. In partial thickness wounds, regeneration is possible from the stem cells in the edges of the wound and from the remnants of the epidermal appendages (such as hair follicles and sebaceous glands). This study examines whether the mechanism of injury influences healing of wounds of similar depth. Burn and excisional wounds were created on the back of Hampshire pigs and harvested at 7, 14, 28, 44, 57 and 70days after injury and processed for histology and immunohistochemistry. Quantitative analysis of re-epithelialisation, inflammatory response and thickness of the scar and semi-quantitative analyses of the architecture of the resultant scar were performed and subjected to statistical analysis. Results demonstrated a higher number of neutrophils, macrophages and lymphocytes present in the burn on day 7 compared to the excisional wounds. The inflammatory profile of burn wounds was higher than that of excisional wounds for the first month after injury albeit less marked than on day 7 after injury. Re-epithelialisation was markedly advanced in excisional wounds compared to burn wounds at day 7 after injury, corresponding to the higher number of hair follicles in the underlying dermis of excisional wounds at this time point. The thickness of the neo-epidermis increased with time and at day 70 after wounding, the neo-epidermis of the burn was significantly thicker than the neo-epidermis of the excisional scar. Interestingly, following partial thickness excision of skin, there was neo-dermal reformation albeit with an altered architecture, lacking the normal basket-weave pattern of collagen. The thickness of the dermis of partial thickness excisional scar was greater than that of the adjacent unwounded skin. The neo-dermis of the burn scar was even thicker, with the collagen arranged more compactly and disorganised compared to excisional scar and normal skin. This study provides evidence that the mechanism of injury does influence wound healing and the resultant scarring.

Asunto(s)