Treatment Of Chronic Skin Wounds Research Articles

Formulative Study and Characterization of Novel Biomaterials Based on Chitosan/Hydrolyzed Collagen Films.

To date, the need for biomaterials capable of improving the treatment of chronic skin wounds remains a clinical challenge. The aim of the present work is to formulate and characterize chitosan (Cs)/hydrolyzed collagen (HC) films as potential biomaterials with improved mechanical and hydration performances compared to single component formulations. Films were made by the solvent casting method, with or without glycerin and/or PEG1500 as plasticizers, resulting in a total of eight formulations. All films were characterized by their physico-chemical characteristics and their mechanical and hydration features. A full factorial design was also used to statistically assess the effect of HC concentration, type and concentration of plasticizers and their possible interactions on mechanical and swelling behaviors. Solid state characterization confirmed the hybrid nature of the films, with suggested electrostatic interactions between Cs and HC. Mechanical and swelling properties, along with the analysis of the experimental design, allowed the identification of formulations containing high HC concentration (2% w/v) and glycerin or glycerin/PEG1500 as more suitable candidates for skin wound treatment. Finally, viability assay of immortalized human keratinocytes (HaCaT) showed no statistical differences in cell survival compared to the complete culture medium, suggesting their potential as a promising tool for biomedical applications.

Microcirculation surrounding end-stage human chronic skin wounds is associated with endoglin/CD146/ALK-1 expression, endothelial cell proliferation and an absence of p16Ink4a.

Angiogenesis is an essential part of normal skin healing, re-establishing blood flow in developing granulation tissue. Non-healing skin wounds are associated with impaired angiogenesis and although the role of re-establishing macroscopic blood flow to limbs to prevent wound chronicity is well investigated, less is known about vascular alterations at the microcirculatory level. We hypothesised that significant phenotypic changes would be evident in blood vessels surrounding chronic skin wounds. Wound edge tissue, proximal to wound (2 cm from wound edge) and non-involved skin (>10 cm from wound edge) was harvested under informed consent from 20 patients undergoing elective amputation due to critical limb ischemia. To assess blood vessel structure and viability, tissue was prepared for histological analysis and labelled with antibodies specific for PECAM-1 (CD31), CD146, endoglin, ALK-1, ALK-5, and p16Ink4a as a marker of cellular senescence. Density of microvasculature was significantly increased in wound edge dermis, which was concomitant with increased labelling for endoglin and CD146. The number of CD31 positive vessel density was unchanged in wound edge tissue relative to non-involved tissue. Co-labelling of endoglin with the transforming growth factor receptor ALK-1, and to a lesser extent ALK-5, demonstrated activation of endothelial cells which correlated with PCNA labelling indicative of proliferation. Analysis of p16Ink4a staining showed a complete lack of immunoreactivity in the vasculature and dermis, although staining was evident in sub-populations of keratinocytes. We conclude that the endoglin-ALK-1-endothelial proliferation axis is active in the vasculature at the edge of chronic skin wounds and is not associated with p16Ink4a mediated senescence. This information could be further used to guide treatment of chronic skin wounds and optimise debridement protocols.

Acceleration of Wound Healing in Rats by Modified Lignocellulose Based Sponge Containing Pentoxifylline Loaded Lecithin/Chitosan Nanoparticles.

Dressing wounds accelerates the re-epithelialization process and changes the inflammatory environment towards healing. In the current study, a lignocellulose sponge containing pentoxifylline (PTX)-loaded lecithin/chitosan nanoparticles (LCNs) was developed to enhance the wound healing rate. Lecithin/chitosan nanoparticles were obtained by the solvent-injection method and characterized in terms of morphology, particle size distribution, and zeta potential. The lignocellulose hydrogels were functionalized through oxidation/amination and freeze-dried to obtain sponges. The prepared sponge was then loaded with LCNs/PTX to control drug release. The nanoparticle containing sponges were characterized using FTIR and SEM analysis. The drug release study from both nanoparticles and sponges was performed in PBS at 37 °C at different time points. The results demonstrated that PTX has sustained release from lignocellulose hydrogels. The wound healing was examined using a standard rat model. The results exhibited that PTX loaded hydrogels could achieve significantly accelerated and enhanced healing compared to the drug free hydrogels and the normal saline treatment. Histological examination of the healed skin confirmed the visual observations. Overall speaking, the in vivo assessment of the developed sponge asserts its suitability as wound dressing for treatment of chronic skin wounds.

Changes in miroRNA-103 expression in wound margin tissue are related to wound healing of diabetes foot ulcers.

To investigate the relationship between small noncoding microRNA-103 (miR-103) and wound healing of diabetic foot ulcers (DFU) and the underlying molecular mechanism, forty type 2 diabetes mellitus with DFU (DFU group), and 20 patients with a chronic skin ulcer of lower limbs and normal glucose tolerance (SUC group) were included. Quantitative real-time PCR method was used to determine miR-103 expression levels in the wound margin tissue of subjects, and to analyse the relationship between the expression of miR-103 and DFU wound healing. In vitro experiments were also performed to understand the effect of miR-103 on the high glucose-induced injury of normal human dermal fibroblasts (NHDFs) cells. The results showed that the miR-103 expression level in the DFU group was significantly higher than that in the SUC group [5.81 (2.25-9.36) vs 2.08 (1.15-5.72)] (P < 0.05). The expression level of miR-103 in the wound margin tissue of DFU was negatively correlated with the healing rate of foot ulcers after four weeks (P=0.037). In vitro experiments revealed that miR-103 could inhibit the proliferation and migration of NHDF cells and promote the apoptosis of NHDF cells by targeted regulation of regulator of calcineurin 1 (RCAN1) gene expression in a high glucose environment. Down-regulation of miR-103 could alleviate high glucose-induced NHDF cell injury by promoting RCAN1 expression. Therefore, the increased expression of miR-103 is involved in the functional damage of NHDF cells induced by high-glucose conditions, which is related to poor wound healing of DFU. These research findings will provide potential targets for the diagnosis and treatment of chronic skin wounds in diabetes.

Zn2+ Cross-Linked Alginate Carrying Hollow Silica Nanoparticles Loaded with RL-QN15 Peptides Provides Promising Treatment for Chronic Skin Wounds.

Chronic and non-healing wounds pose a great challenge to clinical management and patients. Many studies have explored novel interventions against skin wounds, with bioactive peptides, nanoparticles, and hydrogels arousing considerable attention regarding their therapeutic potential. In this study, the prohealing peptide RL-QN15 was loaded into hollow silica nanoparticles (HSNs), with these HSN@RL-QN15 nanocomposites then combined with zinc alginate (ZA) gels to obtain HSN@RL-QN15/ZA hydrogel. The characteristics, biological properties, and safety profiles of the hydrogel composites were then evaluated. Results showed that the hydrogel had good porosity, hemocompatibility, biocompatibility, and broad-spectrum antimicrobial activity, with the slow release of loaded RL-QN15. Further analysis indicated that the hydrogel promoted skin cell proliferation and keratinocyte scratch repair, regulated angiogenesis, reduced inflammation, and accelerated re-epithelialization and granulation tissue formation, resulting in the rapid healing of both full-thickness skin wounds and methicillin-resistant Staphylococcus aureus biofilm-infected chronic wounds in mice. This peptide-based hydrogel provides a novel intervention for the treatment of chronic skin wounds and shows promise as a wound dressing in the field of tissue regeneration.

Beta adrenergic receptor antagonist can modify Pseudomonas aeruginosa biofilm formation in vitro: Implications for chronic wounds.

Non-healing wounds are a major medical challenge, affecting over 6.5million people in the US alone, with associated healthcare costs of about $16 billion annually. They can result in prolonged hospitalizations, work loss, disability, poor quality of life, and in diabetic patients with foot ulcers, amputation of the affected limb in 25% of patients. Though chronic ulcers may arise from different underlying diseases, the unifying feature is chronic infection, driving persistent inflammation that prolongs the healing process. One of the most frequently cultured or genetically identified pathogens in skin wounds is Pseudomonas aeruginosa. This species avidly forms biofilms in the wound that impede bacterial eradication by the host's immune mechanisms and limit efficacy of systemic antibiotics. Thus, non-antibiotic approaches to limit the growth and biofilm formation of this wound pathogen would be an advance in the treatment of chronic wounds. Prior work has demonstrated that the growth of other microbial species can be modulated by catecholamine agonists and antagonists of the adrenergic receptors (ARs). Here, we demonstrate that not only can the growth of this common wound pathogen be modulated by catecholamines, but also that the beta-AR antagonists can significantly decrease their growth, and importantly, limit their ability to form biofilms. These findings suggest that beta adrenergic antagonists may have a therapeutic role in the treatment of chronic skin wounds.

Topical Administration of Heat-Killed Enterococcus faecalis Strain KH2 Promotes Re-Epithelialization and Granulation Tissue Formation during Skin Wound-Healing.

Lactic acid bacteria (LAB) are known to have beneficial effects on immune responses when they are orally administered as bacterial products. Although the beneficial effects of LAB have been reported for the genera Lactobacillus and Lactococcus, little has been uncovered on the effects of the genus Enterococcus on skin wound-healing. In this study, we aimed to clarify the effect of heat-killed Enterococcus faecalis KH2 (heat-killed KH2) strain on the wound-healing process and to evaluate the therapeutic potential in chronic skin wounds. We analyzed percent wound closure, re-epithelialization, and granulation area, and cytokine and growth factor production. We found that heat-killed KH2 contributed to the acceleration of re-epithelialization and the formation of granulation tissue by inducing tumor necrosis factor-α, interleukin-6, basic fibroblast growth factor, transforming growth factor (TGF)-β1, and vascular endothelial growth factor production. In addition, heat-killed KH2 also improved wound closure, which was accompanied by the increased production of TGF-β1 in diabetic mice. Topical administration of heat-killed KH2 might have therapeutic potential for the treatment of chronic skin wounds in diabetes mellitus. In the present study, we concluded that heat-killed KH2 promoted skin wound-healing through the formation of granulation tissues and the production of inflammatory cytokines and growth factors.

Mesenchymal stem cell-derived exosomes: An emerging therapeutic strategy for normal and chronic wound healing.

Skin wound healing is a complex biological process. Mesenchymal stem cells (MSCs) play an important role in skin wound repair due to their multidirectional differentiation potential, hematopoietic support, promotion of stem cell implantation, self-replication, and immune regulation. Exosomes are vesicles with diameters of 40-100 nm that contain nucleic acids, proteins, and lipids and often act as mediators of cell-to-cell communication. Currently, many clinical scientists have carried out cell-free therapy for skin wounds, especially chronic wounds, using exosomes derived from MSCs. This review focuses on the latest research progress on the mechanisms of action associated with the treatment of wound healing with exosomes derived from different MSCs, the latest research progress on the combination of exosomes and other biological or nonbiological factors for the treatment of chronic skin wounds, and the new prospects and development goals of cell-free therapy.

Dual stimuli-responsive polyurethane-based hydrogels as smart drug delivery carriers for the advanced treatment of chronic skin wounds

The design of multi-stimuli-responsive vehicles for the controlled and localized release of drugs is a challenging issue increasingly catching the attention of many research groups working on the advanced treatment of hard-to-close wounds. In this work, a thermo- and pH-responsive hydrogel (P-CHP407) was prepared from an ad hoc synthesized amphiphilic poly(ether urethane) (CHP407) exposing a significant amount of –COOH groups (8.8 ± 0.9 nmol/gpolymer). The exposure of acid moieties in P-CHP407 hydrogel led to slightly lower initial gelation temperature (12.1 °C vs. 14.6 °C, respectively) and gelation rate than CHP407 hydrogel, as rheologically assessed. Nanoscale hydrogel characterization by Low Field NMR (LF-NMR) spectroscopy suggested that the presence of carboxylic groups in P-CHP407 caused the formation of bigger micelles with a thicker hydrated shell than CHP407 hydrogels, as further proved by Dynamic Light Scattering analyses. In addition, P-CHP407 hydrogel showed improved capability to change its internal pH compared to CHP407 one when incubated with an alkaline buffer (pH 8) (e.g., pHchange_5min = 3.76 and 1.32, respectively). Moreover, LF-NMR characterization suggested a stronger alkaline-pH-induced interaction of water molecules with micelles exposing –COOH groups. Lastly, the hydrogels were found biocompatible according to ISO 10993 and able to load and release Ibuprofen: delivery kinetics of Ibuprofen was enhanced by P-CHP407 hydrogels at alkaline pH, suggesting their potential use as smart delivery systems in the treatment of chronic infected wounds.

Using invasive and non-invasive methods to evaluate the therapeutic effect of dielectric barrier discharge (DBD) Plasma in skin graft surgery

Skin graft is effective method to reconstruct large lesions on the skin. Long-term injuries such as burns, skin ulcers, skin flaps, skin grafts... can affect the health of the patient. Skin plays a very important role because it protects the body from dehydration, helps regulate temperature, helps prevent pathogenic bacteria or viruses from entering the body and minimizes skin deformation. In recent years the cold plasma has been used to aid the treatment of chronic skin wounds, burns, ulcers,... To assess the effectiveness of the wound healing process of Plasma, this study uses non – invasive (assess the shrinkage of the wound, the temperature change of the wound) and invasive methods (regeneration of skin tissue structure) to evaluate the therapeutic effects of Dielectric Barrier Dissections Plasma (DBD Plasma) in skin graft surgery. Experimenting with the entire skin graft model on mice, this use of DBD Plasma treatment along with clinical evaluation methods, this is to compare wound healing time between wounds treated with plasma DBD and untreated wound. After 21 days of experimentation, evaluation methods and results processing tools, it was shown that wound healing of skin lesions on mice of the wound area treated with DBD Plasma faster than nontreatment about: (1) The surface shrinkage rate is about 25%; (2) The average wound temperature is less than 0.5-1oC; (3) Healing time is faster from 5 to 6 days. Therefore, DBD Plasma is able to be a potential treatment for wound healing combined with skin graft surgery in the future. The initial study of DBD model is the premise from which could be broader in other animals such as rabbits and pigs with skin structure closer to the human skin. And further, the DBD Plasma shows the potential for preclinical application to human skin graft.

Bioactive Fatty Acids in the Resolution of Chronic Inflammation in Skin Wounds.

Significance: Optimal skin wound healing is crucial for maintaining tissue homeostasis, particularly in response to an injury. The skin immune system is under regulation of mediators such as bioactive lipids and cytokines that can initiate an immune response with controlled inflammation, followed by efficient resolution. However, nutritional deficiency impacts wound healing by hindering fibroblast proliferation, collagen synthesis, and epithelialization, among other crucial functions. In this way, the correct nutritional support of bioactive lipids and of other essential nutrients plays an important role in the outcome of the wound healing process. Recent Advances and Critical Issues: Several studies have revealed the potential role of lipids as a treatment for the healing of skin wounds. Unsaturated fatty acids such as linoleic acid, α-linolenic acid, oleic acid, and most of their bioactive products have shown an effective role as a topical treatment of chronic skin wounds. Their effect, when the treatment starts at day 0, has been observed mainly in the inflammatory phase of the wound healing process. Moreover, some of them were associated with different dressings and were tested for clinical purposes, including pluronic gel, nanocapsules, collagen films and matrices, and polymeric bandages. Therefore, future research is still needed to evaluate these dressing technologies in association with different bioactive fatty acids in a wound healing context. Future Directions: This review summarizes the main results of the available clinical trials and basic research studies and provides evidence-based conclusions. Together, current data encourage the use of bioactive fatty acids for an optimal wound healing resolution.

Lung Surfactant Accelerates Skin Wound Healing: A Translational Study with a Randomized Clinical Phase I Study

Lung surfactants are used for reducing alveolar surface tension in preterm infants to ease breathing. Phospholipid films with surfactant proteins regulate the activity of alveolar macrophages and reduce inflammation. Aberrant skin wound healing is characterized by persistent inflammation. The aim of the study was to investigate if lung surfactant can promote wound healing. Preclinical wound models, e.g. cell scratch assays and full-thickness excisional wounds in mice, and a randomized, phase I clinical trial in healthy human volunteers using a suction blister model were used to study the effect of the commercially available bovine lung surfactant on skin wound repair. Lung surfactant increased migration of keratinocytes in a concentration-dependent manner with no effect on fibroblasts. Significantly reduced expression levels were found for pro-inflammatory and pro-fibrotic genes in murine wounds. Because of these beneficial effects in preclinical experiments, a clinical phase I study was initiated to monitor safety and tolerability of surfactant when applied topically onto human wounds and normal skin. No adverse effects were observed. Subepidermal wounds healed significantly faster with surfactant compared to control. Our study provides lung surfactant as a strong candidate for innovative treatment of chronic skin wounds and as additive for treatment of burn wounds to reduce inflammation and prevent excessive scarring.

To build a well-developed wound repair department in China with the original mind and mission

Based on the spirit of the regulations about diagnosis and treatment of chronic skin wounds just issued by National Health Commission, we systematically review the history of the construction of wound repair department in China and discuss the opportunities and challenges faced by the construction of wound repair department in China. We emphasize on seizing historical opportunities and grasping the development direction of the discipline with the original mind and mission to build a well-developed wound repair department in China, so as to benefit the majority of patients.

The heparin binding domain of von Willebrand factor binds to growth factors and promotes angiogenesis in wound healing

AbstractDuring wound healing, the distribution, availability, and signaling of growth factors (GFs) are orchestrated by their binding to extracellular matrix components in the wound microenvironment. Extracellular matrix proteins have been shown to modulate angiogenesis and promote wound healing through GF binding. The hemostatic protein von Willebrand factor (VWF) released by endothelial cells (ECs) in plasma and in the subendothelial matrix has been shown to regulate angiogenesis; this function is relevant to patients in whom VWF deficiency or dysfunction is associated with vascular malformations. Here, we show that VWF deficiency in mice causes delayed wound healing accompanied by decreased angiogenesis and decreased amounts of angiogenic GFs in the wound. We show that in vitro VWF binds to several GFs, including vascular endothelial growth factor-A (VEGF-A) isoforms and platelet-derived growth factor-BB (PDGF-BB), mainly through the heparin-binding domain (HBD) within the VWF A1 domain. VWF also binds to VEGF-A and fibroblast growth factor-2 (FGF-2) in human plasma and colocalizes with VEGF-A in ECs. Incorporation of the VWF A1 HBD into fibrin matrices enables sequestration and slow release of incorporated GFs. In vivo, VWF A1 HBD-functionalized fibrin matrices increased angiogenesis and GF retention in VWF-deficient mice. Treatment of chronic skin wounds in diabetic mice with VEGF-A165 and PDGF-BB incorporated within VWF A1 HBD-functionalized fibrin matrices accelerated wound healing, with increased angiogenesis and smooth muscle cell proliferation. Therefore, the VWF A1 HBD can function as a GF reservoir, leading to effective angiogenesis and tissue regeneration.

Encapsulation and Characterization of Gentamicin Sulfate in the Collagen Added Electrospun Nanofibers for Skin Regeneration.

In the current practice, the clinical use of conventional skin substitutes such as autogenous skin grafts have shown several problems, mainly with respect to limited sources and donor site morbidity. In order to overcome these limitations, the use of smart synthetic biomaterials is tremendously diffusing as skin substitutes. Indeed, engineered skin grafts or analogues frequently play an important role in the treatment of chronic skin wounds, by supporting the regeneration of newly formed tissue, and at the same time preventing infections during the long-term treatment. In this context, natural proteins such as collagen—natively present in the skin tissue—embedded in synthetic polymers (i.e., PCL) allow the development of micro-structured matrices able to mimic the functions and to structure of the surrounding extracellular matrix. Moreover, the encapsulation of drugs, such as gentamicin sulfate, also improves the bioactivity of nanofibers, due to the efficient loading and a controlled drug release towards the site of interest. Herein, we have done a preliminary investigation on the capability of gentamicin sulfate, loaded into collagen-added nanofibers, for the controlled release in local infection treatments. Experimental studies have demonstrated that collagen added fibers can be efficaciously used to administrate gentamicin for 72 h without any toxic in vitro response, thus emerging as a valid candidate for the therapeutic treatment of infected wounds.

Stromal Cell-Derived Growth Factor-1 Alpha-Elastin Like Peptide Fusion Protein Promotes Cell Migration and Revascularization of Experimental Wounds in Diabetic Mice.

Objective: In previous work, we demonstrated the development of a novel fusion protein containing stromal cell-derived growth factor-1 alpha juxtaposed to an elastin-like peptide (SDF1-ELP), which has similar bioactivity, but is more stable in elastase than SDF1. Herein, we compare the ability of a single topical application of SDF1-ELP to that of SDF1 in healing 1 × 1 cm excisional wounds in diabetic mice. Approach: Human Leukemia-60 cells were used to demonstrate the chemotactic potential of SDF1-ELP versus SDF1 in vitro. Human umbilical vascular endothelial cells were used to demonstrate the angiogenic potential of SDF1-ELP versus SDF1 in vitro. The bioactivity of SDF1-ELP versus SDF1 after incubation in ex-vivo diabetic wound fluid was compared. The in-vivo effectiveness of SDF1-ELP versus SDF1 was compared in diabetic mice wound model by monitoring for the number of CD31+ cells in harvested wound tissues. Results: SDF1-ELP promotes the migration of cells and induces vascularization similar to SDF1 in vitro. SDF1-ELP is more stable in wound fluids compared to SDF1. In vivo, SDF1-ELP induced a higher number of vascular endothelial cells (CD31+ cells) compared to SDF1 and other controls, suggesting increased vascularization. Innovation: While growth factors have been shown to improve wound healing, this strategy is largely ineffective in chronic wounds. In this work, we show that SDF1-ELP is a promising agent for the treatment of chronic skin wounds. Conclusion: The superior in vivo performance and stability of SDF1-ELP makes it a promising agent for the treatment of chronic skin wounds.

The development and characterization of SDF1α-elastin-like-peptide nanoparticles for wound healing

Chronic skin wounds are characterized by poor re-epithelialization, angiogenesis and granulation. Previous work has demonstrated that topical stromal cell-derived growth factor-1 (SDF1) promotes neovascularization, resulting in faster re-epithelialization of skin wounds in diabetic mice. However, the clinical usefulness of such bioactive peptides is limited because they are rapidly degraded in the wound environment due to high levels of proteases. Here, we describe the development of a recombinant fusion protein comprised of SDF1 and an elastin-like peptide that confers the ability to self-assemble into nanoparticles. The fusion protein and recombinant human SDF1 showed similar binding characteristics, as indicated by the measured equilibrium dissociation constant (Kd) for the binding of free SDF1 or the fusion protein to the CXCR4 receptor. The biological activity of SDF1-ELP, as measured by intracellular calcium release in HL60 cells was dose dependent, and also very similar to that of free SDF1. In contrast, the biological activity of SDF1-ELP in vivo was significantly superior to that of free SDF1. When applied to full thickness skin wounds in diabetic mice, wounds treated with SDF1-ELP nanoparticles were 95% closed by day 21, and fully closed by day 28, while wounds treated with free SDF1, ELP alone, or vehicle were only 80% closed by day 21, and took 42days to fully close. In addition, the SDF1-ELP nanoparticles significantly increased the epidermal and dermal layer of the healed wound, as compared to the other groups. These results indicate that SDF1-ELP fusion protein nanoparticles are promising agents for the treatment of chronic skin wounds.

The need to improve

B y now, many of you will already be aware of the systematic review released by a group of researchers from the John Hopkins Evidence-Based Practice Centre and the John Hopkins Wound Healing Centre. A total of 60 research papers focused on the efficacy of various treatments for chronic venous leg ulcers were evaluated, and found to consist of so many methodological faults that any results derived from the studies were deemed unreliable. For busy wound clinicians who may not have time to scour through the literature looking for the most up-to-date and effective treatment options, such systematic reviews are fundamental. This review, however, has inadvertently lead to further confusion and scepticism about the accuracy and reliability of wound care research. The treatment of chronic skin wounds related to poor circulation costs the US approximately $25 billion per year, while in the UK, venous leg ulcers have been estimated to cost the NHS £400 million a year. It is safe to say that funding for wound care research has not been growing in parallel with the burden that chronic wounds are imposing on individuals worldwide. The prevalence of chronic ulcers will indisputably increase along with the growing epidemic of diabetes and obesity. While the effective practice of wound care on patients in the hospital and clinic must improve, it is even more important that the reporting of these practices is bettered. Large, developing nations like India and China, where chronic diseases like diabetes has reached epidemic proportions, look up to the advances in wound care research in developed countries like the UK and the US. The finding from the review that only very weak evidence exists to prove that certain treatments (such as advanced wound dressings or venous surgery) are better than traditional compression therapy or specialised stockings is not an indication that these novel interventions do not work in improving wound healing; it simply implies that there remains a need for welldesigned research studies that can prove that these novel dressings are superior to the current gold standard treatment. In other news, this month’s issue of JWC features a special supplement in collaboration with the Academy of Physicians in Wound Healing (APWH). This will be the first supplement of four to be published this year. This month’s issue also features our cases supplement, the first of three this year, so there is a great variety of articles for you to enjoy. Happy reading!

Cell therapy with human MSCs isolated from the umbilical cord Wharton jelly associated to a PVA membrane in the treatment of chronic skin wounds.

The healing process of the skin is a dynamic procedure mediated through a complex feedback of growth factors secreted by a variety of cells types. Despite the most recent advances in wound healing management and surgical procedures, these techniques still fail up to 50%, so cellular therapies involving mesenchymal stem cells (MSCs) are nowadays a promising treatment of skin ulcers which are a cause of high morbidity. The MSCs modulate the inflammatory local response and induce cell replacing, by a paracrine mode of action, being an important cell therapy for the impaired wound healing. The local application of human MSCs (hMSCs) isolated from the umbilical cord Wharton's jelly together with a poly(vinyl alcohol) hydrogel (PVA) membrane, was tested to promote wound healing in two dogs that were referred for clinical examination at UPVET Hospital, showing non-healing large skin lesions by the standard treatments. The wounds were infiltrated with 1000 cells/µl hMSCs in a total volume of 100 µl per cm2 of lesion area. A PVA membrane was applied to completely cover the wound to prevent its dehydration. Both animals after the treatment demonstrated a significant progress in skin regeneration with decreased extent of ulcerated areas confirmed by histological analysis. The use of Wharton's jelly MSCs associated with a PVA membrane showed promising clinical results for future application in the treatment of chronic wounds in companion animals and humans.

Stem cells and skin regeneration

Stem cells represent a great hope for regenerative medicine. In adult life, stem cell deposits are kept in organ niches; the need for tissue or organ regeneration mobilizes stem cells via the SDF-1-CXCR4 regulation axis. Constant regeneration of the skin is achieved due to stem cell differentiation within the epidermis and the hair follicle; thus, skin may serve as an excellent source of stem cells. This is of paramount importance in the treatment of chronic skin wounds and burns.