Treatment Of Dermal Wounds Research Articles

Human gingival fibroblast secretome accelerates wound healing through anti-inflammatory and pro-angiogenic mechanisms

Healing of the skin and oral mucosa utilises similar mechanisms of tissue repair, however, scarring and the rate of wound closure is vastly superior in the oral cavity suggesting differences between these two environments. One key difference is the phenotype of dermal fibroblasts compared to fibroblasts of gingival tissues. Human gingival fibroblasts (hGFs) are undifferentiated cells with multi-differentiation and self-renewal capacities. This study aimed to examine if delivering hGFs or their secretome, contained in hGF-conditioned media (hGF-CM), would improve healing of the skin and recapitulate features of oral healing. Human fibroblasts, keratinocytes and endothelial cells were first treated with hGF-CM and showed improved migration, proliferation and angiogenic functions. A significant reduction in macroscopic wound area and histologic dermal wound width, as well as an increased rate of re-epithelialisation, were observed in both hGFs and hGF-CM treated murine excisional wounds. This improvement was associated with reduced inflammation, increased angiogenesis and elevated collagen deposition. These findings demonstrate that treatment of dermal wounds with either hGFs or hGF-CM may provide beneficial gingival-like properties to dermal wounds and may be a potential opportunity for improving healing of the skin.

Recombinant Human Hair Keratin Nanoparticles Accelerate Dermal Wound Healing.

In recent years, favorable enhanced wound-healing properties and excellent biocompatibility of keratin derived from human hair have attracted considerable attention. Recombinant keratin proteins can be produced by recombinant DNA technology and have higher purity than extracted keratin. However, the wound-healing properties of recombinant keratin proteins remain unclear. Herein, two recombinant trichocyte keratins including human type I hair keratin 37 and human type II hair keratin 81 were expressed using a bacterial expression system, and recombinant keratin nanoparticles (RKNPs) were prepared via an ultrasonic dispersion method. The molecular weight, purity, and physicochemical properties of the recombinant keratin proteins and nanoparticles were assessed using gel electrophoresis, circular dichroism, mass spectrometry, and scanning electron microscope analyses. The RKNPs significantly enhanced cell proliferation and migration in vitro, and the treatment of dermal wounds in vivo with RKNPs resulted in improved wound healing associated with improved epithelialization, vascularization, and collagen deposition and remodeling. In addition, the in vivo biocompatibility test revealed no systemic toxicity. Overall, this work demonstrates that RKNPs are a promising candidate for enhanced wound healing, and this study opens up new prospects for the development of keratin biomaterials.

N-Acetylglucoseamine modified alginate sponges as scaffolds for skin tissue engineering

In the treatment of dermal wounds, wound-dressing materials prepared from natural mucopolysaccharides are widely used because of their advantages such as nonirritation, nontoxicity, and ease in topical application. In the present study, alginate hydrogels modified with N-acetyl glucose amine (NAG) were prepared as wound-dressing material. Physical, chemical, thermal, and mechanical properties of the hydrogels were studied. Cytotoxicity of the hydrogels on endothelial (HUVEC) and keratinocyte (HaCaT) cells were examined. Anti- and proinflammatory cytokine levels of human monocyte-macrophage cells (THP-1) stimulated with hydrogels were determined. According to the results, increasing the NAG concentration led to an increase in the swelling and nitrogen ratios in the hydrogels. Additionally, increasing the NAG concentration decreased elastic modulus and degradation time. Hydrogels were not cytotoxic on HaCaT and HUVEC cells. It stimulated IL-10 and TNF-alpha levels at a small rate.

Layer-by-Layer Thin Films for Co-Delivery of TGF-β siRNA and Epidermal Growth Factor to Improve Excisional Wound Healing.

The major challenge with treatment of dermal wounds is accelerating healing process, while preventing the scar formation. Herein, we have fabricated layer-by-layer (LbL) polyelectrolyte multilayer films containing epidermal growth factor (EGF) and TGF-β siRNA to improve excisional wound healing and decrease scar formation. The chitosan and sodium alginate LbL thin films showed 13.0MPa tensile strength and 2.22N/cm2 skin adhesion strength. The LbL thin films were found to be cytocompatible, where A431 epidermal keratinocytes adhered to the film and showed 86.2 ± 0.8% cell growth compared with cells cultured in the absence of LbL thin film. In contrast, LbL thin film did not promote the Escherichia coli and Staphylococcus aureus bacterial colony formation. In a C57BL/6 mouse excisional wound model, application of LbL thin films containing TGF-β siRNA significantly (p < 0.05) reduced the TGF-β protein expression and collagen production. The LbL thin films containing EGF showed improved wound contraction (<9days post excision). The co-delivery of TGF-β siRNA and EGF using LbL thin films resulted in accelerated wound healing and decreased collagen deposition. Furthermore, the LbL thin films with TGF-β siRNA and EGF combination showed greater reepithelialization. Taken together, we have successfully demonstrated the co-delivery of TGF-β siRNA and EGF peptide using LbL thin films to promote wound healing and decrease scar formation.

Hexane extract of the seeds of Byrsonima crassifolia accelerates wound healing in streptozotocin-induced diabetic rats.

To study the effect of seeds of Byrsonima crassifolia in diabetic wound healing. Wound healing potential of hexane extract in the form of simple ointment for the treatment of dermal wounds was studied in streptozotocin-induced diabetic rats on excision wound, incision wound and dead space wound. Various parameters such as epithelization period, scar area, tensile strength, hydroxyproline, total protein, DNA, hexosamine, uronic acid, antioxidant enzymes including superoxide dismutase (SOD) and catalase activity (CAT) were used to evaluate the effect of B. crassifolia on wound healing. Hexane extract in form topical accelerates the wound healing process by decreasing the surface area of the wound with a significant increase in the rate of wound contraction and tensile strength; increase granulation tissue dry weight, hydroxyproline, total protein, DNA and SOD and CAT when compared with diabetic control. B. crassifolia was effective in promoting diabetic wound healing in rats through the processes of tissue regeneration.

Stem cell therapy for dermal wound healing.

The use of cellular therapy in the treatment of dermal wounds is currently an active area of investigation. Multipotent adult stem cells are an attractive choice for cell therapy because they have a large proliferative potential, the ability to differentiate into different cell types and produce a variety cytokines and growth factors important to wound healing. This review focused on the roles of adult stem cells such as endothelial progenitor cells, bone marrow and adipose-derived mesenchymal stem cells, during dermal wound healing process and their therapeutic potentials for the treatment of chronic wounds, which remain a major clinical problem, especially in diabetic patients.

New cucurbitacin derivatives from Bryonia aspera Stev. ex Ledeb

Bryonia aspera Stev. ex Ledeb from the Cucurbitaceae family is native to Iran. This plant has been described in an ethnobotanical study as being used as a treatment of dermal wounds, cancer and digestive disorders [1], whereas no phytochemical investigations have been reported up to now. The isolation of bioactive compounds from this plant seemed to be of interest because a chloroform extract showed cytotoxic activity. Therefore a phytochemical investigation of the root extract has been undertaken and yielded 11 compounds. Their structures were elucidated by spectroscopic means (1D- and 2D-NMR spectroscopy, ESI-MS). The majority of the compounds turned out to be 23,24-dihydro-cucurbitacin derivatives.

Multipotent adult progenitor cells: their role in wound healing and the treatment of dermal wounds

The use of cellular therapy in the treatment of dermal wounds is currently an active area of investigation. Multipotent adult progenitor cells (MAPC) are an attractive choice for cytotherapy because they have a large proliferative potential, the ability to differentiate into different cell types and produce a variety of cytokines and growth factors important to wound healing. Whole bone marrow (BM) was one of the initial attempts to treat impaired wounds. While it has shown some promise, the low frequency of progenitor cell populations in BM and the large number of inflammatory cells make it less attractive. Multipotent mesenchymal stromal cells (MSC) and endothelial progenitor cells are populations of BM-derived progenitor cells that have been isolated and used to treat chronic wounds with some success. Skin-derived MAPC are another heterogeneous population of progenitor cells present in the skin with the potential to differentiate into skin elements and participate in wound healing. All of these progenitor cell populations are potential sources for cytotherapy of wounds. This review focused on the contribution of adult progenitor cell populations to dermal wound healing and their potential for use in cytotherapy.

Preparation of Fucoidan-Chitosan Hydrogel and Its Application as Burn Healing Accelerator on Rabbits

Treatment of dermal wounds with macromolecular agents such as natural polymers is one of the research areas of the biomaterial science. Fucoidan is a sulphated polysaccharide which is commonly obtained from seaweeds. The great number of studies on the different pharmacological properties of fucoidan is present, but there is limited information about using of fucoidan in the treatment of dermal burns. The aim of this study was to prepare fucoidan-chitosan hydrogels and to investigate their treatment efficiency on dermal burns. Hydrogels were prepared by swelling the polymers in acidic solution and their swelling, mechanical (hardness, cohesiveness and adhesiveness) and bioadhesive properties were investigated. The viscosity and water absorption capacity of formulations increased with increase in the polymer concentration. In contrast to the cohesiveness results, the adhesiveness of hydrogels increased with the polymer concentration. The bioadhesion was changed between 0.012-0.142 mJ x cm(-2) and enhanced with addition of fucoidan into gel formulations. It was formed dermal burns on seven adult male New Zealand white rabbits and the optimum gel formulation applied on the wounds. Control and treatment group biopsy samples were taken on days 7, 14 and 21 and each burn wound site was evaluated histopathologically. No edema was seen in tested groups except control after 3 d treatment. After 7 d treatment, fibroplasia and scar were fixed on wounds treated with fucoidan-chitosan gel and fucoidan solution. The best regeneration on dermal papillary formation and the fastest closure of the wounds were observed in fucoidan-chitosan hydrogels after 14 d treatment.

Evaluation of electrospun PCL/gelatin nanofibrous scaffold for wound healing and layered dermal reconstitution

The current design requirement for a tissue engineering skin substitute is that of a biodegradable scaffold through which fibroblasts can migrate and populate. This artificial “dermal layer” needs to adhere to and integrate with the wound, which is not always successful for the current artificial dermal analogues available. The high cost of these artificial dermal analogues also makes their application prohibitive both to surgeons and patients. We propose a cost-effective composite consisting of a nanofibrous scaffold directly electrospun onto a polyurethane dressing (Tegaderm™, 3M Medical) – which we call the Tegaderm-nanofiber (TG-NF) construct – for dermal wound healing. Cell culture is performed on both sides of the nanofibrous scaffold and tested for fibroblast adhesion and proliferation. It is hoped that these studies will result in a fibroblast-populated three-dimensional dermal analogue that is feasible for layered applications to build up thickness of dermis prior to re-epithelialization. Results obtained in this study suggest that both the TG-NF construct and dual-sided fibroblast-populated nanofiber construct achieved significant cell adhesion, growth and proliferation. This is a successful first step for the nanofiber construct in establishing itself as a suitable three-dimensional scaffold for autogenous fibroblast populations, and providing great potential in the treatment of dermal wounds through layered application.

Acceleration of wound healing in aged rats by topical application of transforming growth factor‐β1

The impaired wound healing associated with aging may reflect inadequate secretion or delivery of cytokines. Transforming growth factor-beta(1) is a mitogenic polypeptide with beneficial effects on wound healing. In the present study we questioned whether topical administration of transforming growth factor-beta(1) could improve the wound healing process in aged rats in vivo. Wound repair (from 1 to 14 days) was analyzed in full-thickness incisional wounds from 2-year-old rats with or without a single topical application of transforming growth factor-beta(1) (1 microg/wound) at the time of wounding. Identical wounds from 3-month-old, untreated rats served as controls. Histologic analysis showed a marked delay in several aspects of wound repair in the aged rats in comparison with that noted in the younger animals. Immunostaining of the wounds for proliferating cell nuclear antigen showed a reduction in the number of cycling fibroblasts in old rats. In addition, the number of capillaries per unit area of the wound as determined by a stain for Griffonin (Bandeiraea) simplicifolia lectin, and the number of inflammatory cells as identified by an antibody specific for macrophages, were also reduced in the wound area in old rats. Treatment with transforming growth factor-beta(1) resulted in marked enhancement of the following parameters: cell proliferation, inflammatory cell and fibroblast influx, wound closure, and angiogenesis. As seen with in situ hybridization, a similar temporal pattern of expression of messenger RNAs corresponding to type I procollagen and Secreted Protein, Acidic and Rich in Cysteine (osteonectin), known to be prevalent in healing wounds, was observed in both young and aged rats. However, the levels of mRNA corresponding to these secreted proteins appeared to be reduced in wound tissue from aged rats. Treatment with transforming growth factor-beta(1) subsequently resulted in an increase in the expression of both type I procollagen and Secreted Protein, Acidic and Rich in Cysteine mRNA in the wound tissue from aged rats. In summary, a single topical application of transforming growth factor-beta(1) to the wounds of aged rats at the time of wounding was associated with a healing response that, in all the parameters of wound repair examined, was similar to that of young rats. Topical transforming growth factor-beta(1) might therefore be beneficial in the treatment of dermal wounds in the aged.