Different therapies that modulate wound repair have been proposed over the last few decades. This article reviews the two emerging fields of gene and stem cell therapy in wound healing. Gene therapy, initially developed for treatment of congenital defects, is a new option for enhancing wound repair. In order to accelerate wound closure, genes encoding for growth factors or cytokines have showed the most potential. The majority of gene delivery systems are based on viral transfection, naked DNA application, high pressure injection, or liposomal vectors. Embryonic and adult stem cells have a prolonged self renewal capacity with the ability to differentiate into various tissue types. A variety of sources, such as bone marrow, peripheral blood, umbilical cord blood, adipose tissue, skin and hair follicles, have been utilized to isolate stem cells to modulate the healing response of acute and chronic wounds. Recently, the combination of gene and stem cell therapy has emerged as a promising approach for future treatment of chronic and acute wounds.
Gene therapy was traditionally considered a treatment modality for patients with congenital defects of key metabolic functions or late-stage malignancies. The realization that gene therapy applications were much vaster has opened up endless opportunities for therapeutic genetic manipulations, especially in the skin and external wounds. Cutaneous wound healing is a complicated, multistep process with numerous mediators that act in a network of activation and inhibition processes. Gene delivery in this environment poses a particular challenge. Numerous models of gene delivery have been developed, including naked DNA application, viral transfection, high-pressure injection, liposomal delivery, and more. Of the various methods for gene transfer, cationic cholesterol-containing liposomal constructs are emerging as a method with great potential for non-viral gene transfer in the wound. This article aims to review the research on gene therapy in wound healing and possible future directions in this exciting field.
Currently, there are various therapeutic approaches to reduce hypertrophic scarring; however, there is no standard evidence-based treatment protocol. Hence, a systematic review was performed to obtain a summary of the latest clinical trials to evaluate evidence for the treatment of hypertrophic scars. The review protocol was registered and approved by PROSPERO (CRD42015027040). PubMed and Web of Science were searched using predefined MeSH-Terms to identify studies published within the last 10 years regarding treatment for hypertrophic scars. Exclusion criteria included a level of evidence (LoE) lower than I, nonhuman in vivo studies, in vitro studies, studies on keloids, literature reviews, and non-English articles. The literature search identified 1,029 unique articles, whereas 6 articles were prospective, randomized, blinded, controlled clinical trials with a LoE I, and were thus included in the systematic analysis. Three clinical trials evaluated silicone products and pressure garments, and the other three studies investigated the efficacy of intralesional injections of triamcinolone (TAC), 5-Fluorouracil (5-FU) combined with TAC as well as the additional irradiation with a 585 nm pulsed-dye laser (PDL). Intralesional injections revealed significant improvements of the scar quality in terms of height, thickness, erythema, and pigmentation. Pressure garments showed favorable results but there was no evidence that silicone products were able to improve the scar quality. The systematic review demonstrated that there are just a few clinical trials with a LoE of I. Consequently, evidence is still lacking especially for noninvasive treatment regimens for hypertrophic scars. Intralesional injections of 5-FU mixed with a low dose of TAC can be seen as most appropriate treatment modality. Prospective clinical trials to determine the efficiency of silicone products are warranted.
Modern burn care has led to unprecedented survival rates in burn patients whose injuries were fatal a few decades ago. Along with improved survival, new challenges have emerged in the management of burn patients. Infections top the list of the most common complication after burns, and sepsis is the leading cause of death in both adult and pediatric burn patients. The diagnosis and management of sepsis in burns is complex as a tremendous hypermetabolic response secondary to burn injury can be superimposed on systemic infection, leading to organ dysfunction. The management of a septic burn patient represents a challenging scenario that is commonly encountered by providers caring for burn patients despite preventive efforts. Here, we discuss the current perspectives in the diagnosis and treatment of sepsis and septic shock in burn patients.
Improvements in burn wound care have vastly decreased morbidity and mortality in severely burned patients. Development of new therapeutic approaches to increase wound repair has the potential to reduce infection, graft rejection, and hypertrophic scarring. The incorporation of tissue engineering techniques, along with the use of exogenous proteins, genes, or stem cells to enhance wound healing, heralds new treatment regimens based on the modification of already existing biological activity. Refinements to surgical techniques have enabled the creation of protocols for full facial transplantation. With new technologies and advances such as these, care of the severely burned will undergo massive changes over the next decade. This review centers on new developments that have recently shown great promise in the investigational arena.
Major advances in burn care have reduced post-burn morbidity and mortality. The development and incorporation of new wound healing modalities into the clinical arena have contributed to this improvement by allowing standard-of-care regimens to be established. These regimens range from early excision to the use of cultured epithelial autograft. Here, we review the wound care options that are now well established and used by many burn surgeons.
Over the past three decades the syndrome now commonly referred to as sepsis has alternately been called sepsis syndrome, septicemia, and simply sepsis. 7 Currently, the
Controlled delivery of growth factors from biodegradable biomatrices could accelerate and improve impaired wound healing. The study aim was to determine whether platelet-derived growth factor AB (PDGF.AB) with a transglutaminase (TG) crosslinking substrate site released from a fibrin biomatrix improves wound healing in severe thermal injury. The binding and release kinetics of TG-PDGF.AB were determined in vitro. Third-degree contact burns (dorsum of Yorkshire pigs) underwent epifascial necrosectomy 24 h post-burn. Wound sites were covered with autologous meshed (3:1) split-thickness skin autografts and either secured with staples or attached with sprayed fibrin sealant (FS; n = 8/group). TG-PDGF.AB binds to the fibrin biomatrix using the TG activity of factor XIIIa, and is subsequently released through enzymatic cleavage. Three doses of TG-PDGF.AB in FS (100 ng, 1 µg and 11 µg/ml FS) were tested. TG-PDGF.AB was bound to the fibrin biomatrix as evidenced by western blot analysis and subsequently released by enzymatic cleavage. A significantly accelerated and improved wound healing was achieved using sprayed FS containing TG-PDGF.AB compared to staples alone. Low concentrations (100 ng-1 µg TG-PDGF.AB/ml final FS clot) demonstrated to be sufficient to attain a nearly complete closure of mesh interstices 14 days after grafting. TG-PDGF.AB incorporated in FS via a specific binding technology was shown to be effective in grafted third-degree burn wounds. The adhesive properties of the fibrin matrix in conjunction with the prolonged growth factor stimulus enabled by this binding technology could be favourable in many pathological situations associated with wound-healing disturbances. Copyright © 2013 John Wiley & Sons, Ltd.
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