Oxygen Therapy to Enhance Wound Healing After Revascularization.

Oxygen is one of the important factors for wound healing and infection control. The revascularization procedure is amended to correct the tissue hypoxia problem by increasing the blood flow to obtain an adequate amount of oxygen. Hypoxic wounds are still the issue in the cases of unsuccessful or incomplete revascularization. The issue needs to be clarified and confirmed by proper methods for management to achieve wound healing and prevent limb loss. Oxygen therapy may benefit in the case of remaining hypoxia or wound infection in postrevascularization.

Translational application of human keratinocyte-fibroblast cell sheets for accelerated wound healing in a clinically relevant type 2 diabetic rat model.

BACKGROUND AIMS: Despite advancements in wound care, wound healing remains a challenge, especially in individuals with type 2 diabetes. Cell sheet technology has emerged as an efficient and promising therapy for tissue regeneration and wound repair. Among these, bilayered human keratinocyte-fibroblast cell sheets constructed using temperature-responsive culture surfaces have been shown to mimic a normal tissue-like structure and secrete essential cytokines and growth factors that regulate the wound healing process. METHODS: This study aimed to evaluate the safety and therapeutic potential of human skin cell sheets to treat full-thickness skin defects in a rat model of type 2 diabetes. RESULTS: Our findings demonstrate that diabetic wounds transplanted with bilayered cell sheets resulted in accelerated re-epithelialization, increased angiogenesis, enhanced macrophage polarization and regeneration of tissue that closely resembled healthy skin. In contrast, the control group that did not receive cell sheet transplantation presented characteristic symptoms of impaired and delayed wound healing associated with type 2 diabetes. CONCLUSIONS: The secretory cytokines and the upregulation of Nrf2 expression in response to cell sheet transplantation are believed to have played a key role in the improved wound healing observed in diabetic rats. Our study suggests that human keratinocyte-fibroblast cell sheets hold great potential as a therapeutic alternative for diabetic ulcers.

Expansion of fibroblast cell sheets using a modified MEEK micrografting technique for wound healing applications.

Cell sheet engineering, a scaffold-free approach to fabricate functional tissue constructs from several cell monolayers, has shown promise in tissue regeneration and wound healing. Unfortunately, these cell sheets are often too small to provide sufficient wound area coverage. In this study, we describe a process to enlarge cell sheets using MEEK micrografting, a technique extensively used to expand skin autografts for large burn treatments. Human dermal fibroblast cell sheets were placed on MEEK's prefolded gauze without any use of adhesive, cut along the premarked lines and stretched out at various expansion ratios (1:3, 1:6 and 1:9), resulting in regular distribution of many square islands of fibroblasts at a much larger surface area. The cellular processes essential for wound healing, including reattachment, proliferation, and migration, of the fibroblasts on expanded MEEK gauze were superior to those on nylon dressing which served as a control. The optimal expansion ratio with the highest migration rate was 1:6, possibly due to the activation of chemical signals caused by mechanical stretching and an effective intercellular communication distance. Therefore, the combination of cell sheet engineering with the MEEK micrografting technique could provide high quality cells with a large coverage area, which would be particularly beneficial in wound care applications.

Preparation and characterization of human keratinocyte-fibroblast cell sheets constructed using PNIAM-co-AM grafted surfaces for burn wound healing.

Autologous skin grafting, the standard treatment for severe burns, is sometimes not possible due to the limited available skin surfaces for the procedure. With advances in tissue engineering, various cell-based skin substitutes have been developed to serve as skin replacements and to promote tissue regeneration and healing. In this work, we propose the use of cell sheet technology to fabricate keratinocyte-fibroblast tissue constructs from the temperature-responsive poly(N-isoproprylacrylamide-co-acrylamide) (PNIAM-co-AM) grafted surfaces for the treatment of burn wounds. The characteristics of the human keratinocyte and fibroblast cell sheets harvested using PNIAM-co-AM grafted surfaces were similar to those cell sheets detached from the commercially-available UpCellTM plates. Upon lowering the incubation temperature, confluent keratinocytes and fibroblasts could be detached as intact sheets, consisting of biologically active cells, as indicated by their high cell viability and their reattachment, migratory, and proliferative activities. A histological analysis of the stratified keratinocyte-fibroblast cell sheets revealed the evidence of cell migration and tissue reorganization to form two distinct epidermal and dermal layers, quite similar to the skin tissue's structure. In addition, the keratinocyte-fibroblast sheets could synthesize and release significant amounts of essential cytokines and growth factors involved in regulating the wound healing process, including IL-1α, IL-6, TNF-α, VEGF, and bFGF, implying the therapeutic effect of these cell sheets, which could be beneficial to accelerate tissue repair and regeneration, leading to faster wound healing.

Polyurethane-biomacromolecule combined foam dressing containing asiaticoside: fabrication, characterization and clinical efficacy for traumatic dermal wound treatment.

Polyurethane combined (PUC) foam dressings with various biomacromolecules were fabricated with the adsorption of asiaticoside and silver nanoparticles for traumatic wound treatment. Biomacromolecules had varying effects on physicochemical and mechanical properties of PU foam. With 2% incorporation, starches, high molecular weight chitosan and gelatin provided stiffer and more porous foams while carboxymethylcellulose had the highest compression strength but the lowest water vapor transmission. High water absorption was from foams with carboxymethylcellulose, alginate, hydroxypropyl methylcellulose and low molecular weight chitosan. Increasing the concentrations up to 12% had more prominent effect. However, powdery surface was noticed with poorer tensile properties that 6% incorporation was selected. FTIR spectra and DSC thermograms suggested interaction of PU formulation with biomacromolecules. EDS analysis confirmed existence of active compounds while acceptable stability was from sterilized PUC foam with alginate. On healthy volunteers, this selected foam dressing caused no skin irritation and retained moisture comparable to commercial product. In patients with traumatic dermal wounds, healing improvement with shorter wound closure time, higher reepithelialization and less pain score were from the selected foam dressing compared to standard gauze soaked with chlorhexidine. This PU-alginate combined foam dressing adsorbed with asiaticoside and silver nanoparticles proved advantages for traumatic dermal wound management.

Randomized Controlled Trial of Polyhexanide/Betaine Gel Versus Silver Sulfadiazine for Partial-Thickness Burn Treatment.

Silver sulfadiazine is commonly used in the treatment of partial-thickness burns, but it sometimes forms pseudo-eschar and delays wound healing. Polyhexanide/betaine gel, a new wound cleansing and moisturizing product, has some advantages in removing biofilm and promotes wound healing. This study was designed to compare clinical efficacy of polyhexanide/betaine gel with silver sulfadiazine in partial-thickness burn treatment. From September 2013 to May 2015, 46 adult patients with partial-thickness burn ≥10% total body surface area that were admitted to the Burn Unit of Siriraj Hospital within 48 hours after injury were randomly allocated into 2 groups. One group was treated with polyhexanide/betaine gel, and the other group was treated with silver sulfadiazine. Both groups received daily dressing changes and the same standard care given to patients with burns in this center. Healing times in the polyhexanide/betaine gel group and silver sulfadiazine group were 17.8 ± 2.2 days and 18.8 ± 2.1 days, respectively ( P value .13). There were no significant differences in healing times, infection rates, bacterial colonization rates, and treatment cost in both groups. The pain score of the polyhexanide/betaine gel group was significantly less than the silver sulfadiazine group at 4 to 9 days after treatment ( P < .001). The satisfactory assessment result of the polyhexanide/betaine gel group was better than that in the silver sulfadiazine group. These data indicate the need for adequately designed studies to elicit the full potential of polyhexanide gel as a wound dressing for partial-thickness burn wounds.

Clinical Efficacy Test of Polyester Containing Herbal Extract Dressings in Burn Wound Healing.

Technological advancement has assisted in developing various availabilities of wound products that help in not only in healing and preventing infection but also in providing patients' comfort and pain reduction during application. However, most of advanced wound healing products in Thailand were imported at high costs to patients. Nowadays, there are increased numbers of local researches of herbs that could provide healing environment for successful wound care. Herbal wound products are currently being introduced as alternatives to those imported dressings. The aim of this study was to report the clinical efficacy of using polyester containing herbal extract dressings in healing of second-degree burns. The volunteers were divided by simply randomized method into the study group of patient using polyester containing herbal extract dressing and the control group of patients treating with dressings that are commercially available and common use. The standard treatment protocols were performed at every 3 days of dressing change. Comparative evaluation consisted of time of healing, length of hospital stays, pain analog score assessment, percentage of infection, and descriptive notification of unfavorable clinical symptoms or signs or side effects.