Full-thickness Burn Wounds Research Articles

Preclinical evaluation of the polycaprolactone-polyethylene glycol electrospun nanofibers containing egg-yolk oil for acceleration of full thickness burns healing

Considering the great potential of egg yolk oil (EYO) in management of burn wounds and superb biological properties of polycaprolactone (PCL) and polyethylene glycol (PEG), hereby, a PCL-PEG-EYO scaffold was developed by electrospinning method for burn healing. The physico-chemical characterizations were performed using SEM, FTIR and contact angle tests. The biological properties of the fabricated scaffolds were evaluated by antibacterial test, in vitro cell culturing, MTT assay and in vivo experiments. The SEM images of PCL-PEG-EYO nanofibers demonstrated a uniform bead-free morphology with 191 ± 61 nm diameter. The fabricated scaffold revealed hydrophilicity with the water contact angel of 77°. No cytotoxicity was observed up to 7 days after cell culturing onto the PCL-PEG-EYO nanofibrous surface. The presence of EYO in the PCL-PEG-EYO scaffold meaningfully improved the cell viability, proliferation and attachment compared to PCL-PEG scaffold. Moreover, the PCL-PEG-EYO scaffolds demonstrated antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa bacteria strain. Finally, a statistically significant enhancement in wound closure, re-epithelialization, angiogenesis and collagen synthesis was observed at the end of 21-day treatment period using PCL-PEG-EYO nanofibrous scaffold. Overall, the PCL-PEG-EYO nanofibrous scaffolds demonstrated a great potential in management of full thickness burn wounds in vivo.

Potential antibacterial activity and healing effect of topical administration of bone marrow and adipose mesenchymal stem cells encapsulated in collagen-fibrin hydrogel scaffold on full-thickness burn wound infection caused by Pseudomonas aeruginosa

Burns injuries are prone to hospital-acquired infections, and Pseudomonas aeruginosa is one of the most common causes of mortality and morbidity in patients with burn injuries. Thus, this study aimed to analyze the effects of topical treatment with bone marrow (BM-MSC) and adipose mesenchymal stem cells (AD-MSC) encapsulated in collagen and fibrin scaffolds in a Balb/c model of burn wound infection. Extraction of stem cells from adipose and bone marrow tissue of rats was performed and cells were characterized using standard methods. Then, collagen, fibrin and collagen-fibrin scaffolds were constructed and the extracted cells were encapsulated in all three scaffolds. Then, 3rd degree burn was induced in mice and 1.5 × 108 (CFU/ml) of P. aeruginosa was introduced to the burn wound. Subsequently, after 24 h of inducing wound infection, encapsulated MSCs were introduced as dressings to burn wound infection and microbial load as well as rate of wound infection healing was measured. The results of this study showed that the use of BM-MSC and AD-MSC encapsulated in collagen-fibrin scaffold reduced the bacteria load down to 54 and 21 CFU/gr, respectively (P < 0.05). Moreover, BM-MSC and AD-MSC encapsulated in collagen-fibrin showed 80% and 75% wound healing, respectively (P < 0.05). Also, we found no significant between cell origin and healing. Encapsulation of MSCs into collagen-fibrin scaffolds could be effective not only against P. aeruginosa infection, but also healing and regeneration of burn wound.

Characterization of Stromal Vascular Fraction Harvested from Inguinal Fat of Rabbit for Healing of Full Thickness Burn Wound

Characterization of Stromal Vascular Fraction Harvested from Inguinal Fat of Rabbit for Healing of Full Thickness Burn Wound

Biomimetic multifunctional hybrid sponge via enzymatic cross-linking to accelerate infected burn wound healing

Preparing sponge dressings with stable wet adhesion remains difficult in wound repair, especially in burn wounds with bleeding and large amounts of exudate. In this work, a multifunctional hybrid sponge dressing (DHGT+PHMB+TiO2NPs) with good wet adhesion was developed by combining biomimetic and enzymatic cross-linking reactions. The sponge dressing matrix (DHGT) was prepared by tyrosinase-catalyzed cross-linking of dopamine-modified hyaluronic acid (DOPA-HA) and gelatin. The multifunctional hybrid sponge dressing was obtained by loading polyhexamethylene biguanide (PHMB) and titanium dioxide nanoparticles (TiO2NPs) onto the DHGT matrix. The newly developed sponge dressing exhibited high mechanical properties, good wet adhesion, antibacterial activity, reactive oxygen species (ROS) scavenging, biocompatibility, and excellent hemostasis ability. In vivo studies showed that the multifunctional hybrid sponge dressing could significantly accelerate the healing of infected full-thickness burn wounds by inhibiting bacterial growth, accelerating skin tissue reepithelialization, collagen deposition, and angiogenesis, as well as regulating the expression of inflammatory factors and cytokines.

Amino acid buffered hypochlorite facilitates debridement of porcine infected burn wounds

IntroductionRemoval of necrotic tissue is a vital step in the treatment of full-thickness burn wounds, with surgical debridement being the most effective method. Since minor burn wounds are typically treated on an outpatient basis where surgical capabilities can be limited there is a need for alternative treatment options. In this study we aim to evaluate the use of amino acid buffered hypochlorite (AABH) as a chemical enhancement for wound debridement in a porcine infected burn wound model. MethodA total of 60 full-thickness burn wounds, 3 cm in diameter, were created on four pigs using a standardized burn device. The wounds were inoculated with 107 colony-forming units (CFU) of S. aureus. The experimental groups included wounds debrided with a plastic curette, wounds debrided after pretreatment with AABH, and control wounds wiped with gauze. Wounds were treated twice per week for three weeks. Debridement, healing, and infection parameters were evaluated over time. ResultsAfter one week, but not after two and three weeks, the curette and AABH groups had higher debrided weights compared to control (p < 0.05). Percentage of wound area adequately cleared from necrotic tissue was higher in the AABH-group compared to the curette-group and control, after one week. The earliest healing was measured in the AABH group after two weeks (5 % of wounds), which also had the most healed wounds after three weeks (55 %). In both the AABH and the curette groups, bacterial load had fallen below 105 CFU/g after two weeks. No CFU were detectable in the AABH group after three weeks. The AABH-group was also the easiest to debride. ConclusionOur results indicate that AABH facilitates wound debridement and could be a helpful addition to an effective treatment modality for removal of necrotic tissue in full-thickness burns.

Wound healing and anti-inflammatory effects of recombinant human angiogenin

New effective wound healing agents are a priority for modern clinical pharmacology. A promising approach would be to develop medicinal products that promote angiogenesis, which is a critical step in wound healing. The aim of the study was to evaluate the wound healing effect of a medicinal product based on recombinant human angiogenin in gel form in various experimental models. Materials and methods: white outbred male rats were used as experimental ani mals. The study compared healing effects of a regenerating product containing recombinant human angiogenin (0.0025%) in gel form and a reference product in full-thickness excision, incision, and burn wound models. The healing effect of the test product in treating chronic wounds was assessed in a model of alloxan-induced diabetes mellitus. The anti-inflammatory effect of the test product containing recombinant human angiogenin was compared with that of another reference product in a model of adjuvant-induced arthritis. Results: according to the study, the test product based on recombinant human angiogenin exerts higher wound healing effect in treating excision, incision, and burn wounds than the reference product (Solcoseryl gel). Being applied, the test product intensifies tissue repair in chronic wounds in the model of alloxan-induced diabetes. The dissociation of necrotic tissues and the progression towards epithelialisation at wound edges are more rapid. The anti-inflammatory effect of the test product based on recombinant human angiogenin is comparable with that of the reference product (Diclofenac gel). Conclusions: the test product based on recombinant human angiogenin in gel form was found to have pronounced wound healing and anti-inflammatory effects comparable with those of reference products.

The predictive probability of mortality in the presence of full-thickness burns

IntroductionPrognostication of burn injury mortality is challenging. Recent mortality prognostication tools have incorporated the percent of full-thickness surface area (FTSA). We hypothesize that the presence of full-thickness burn injury independently increases in-hospital mortality. MethodsWe performed a retrospective review of the National Trauma Data Bank (NTDB) from 2007 to 2019 of adults (≥16 years old) with burn injuries. Variables evaluated included basic demographics, presence of inhalation injury, percent TBSA, and percent FTSA burned. The primary outcome was in-hospital mortality. We performed modified Poisson regression modeling adjusting for significant variables to estimate the relative mortality risk. Results75,816 patients met inclusion criteria. When controlling for TBSA, the presence of a full-thickness burn had a relative risk of in-hospital mortality of 1.42 (95% CI 1.09–1.85, p = 0.008). The predicted probability of mortality was 100% at 50% FTSA. ConclusionThe presence of full-thickness burns and the proportion of full-thickness burns independently and significantly increased in-hospital mortality. Therefore, clinicians should utilize prognostication models incorporating percent full-thickness burn area to predict mortality more accurately.

Effects of resveratrol topical ointment on wound healing of full-thickness cutaneous burns in albino rats.

In this study, the effects of resveratrol topical ointment on wound contraction and histopathology of full-thickness cutaneous burn wounds were evaluated. Adult albino rats were grouped into four equal-sized groups of 15 rats each, as follows: Group A-no wound, no treatment (control); Group B-1% silver sulphadiazine; Group C-5% resveratrol, and Group D-wound without treatment (control). A burn wound measuring 23.5mm was created on the skin at the dorsum of all rats in groups B-D after shaving. The percentage of wound contraction was measured using a digital Vernier Caliper on days 1, 3, 5, 7, 10, 14, 16, 18 and 21, post-wounding. From each group, five rats were then euthanised and tissue samples of the skin, liver and kidney were collected in 10% buffered formalin for histopathology. The percentage of wound contraction was significant (p<0.05) on 7, 14 and 18 days post treatment. Histopathologically, 5% resveratrol topical ointment application resulted in a thicker epidermis with neovascularisation and an increased collagen distribution. Resveratrol topical ointment ameliorated the extent of hepatocellular and nephrotubular injuries following burn-induced hepatocellular and acute kidney injuries. In this study, topical application of 5% resveratrol ointment appeared to enhance burn wound healing by increasing the rate of wound contraction through collagen fibre synthesis, granulation tissue formation and epithelial regeneration.

Preliminary Single-Center Experience of Bromelain-Based Eschar Removal in Children with Mixed Deep Dermal and Full Thickness Burns.

Introduction: Early eschar removal is the standard management of burns. The goal is to remove all of the necrotic tissue and render the wound suitable for healing or skin grafting. The enzymatic debridement of burn wounds allows for minimally invasive removal of burn eschar. The aim of the study was to describe and compare the demographic characteristics, surgical treatment and outcomes of patients treated with Nexobrid® with patients who had standard surgical excision. Material and Methods: A retrospective review was conducted on children who underwent enzymatic debridement. The study group was compared with children treated with the standard of care (SoC). Results: Twelve children (mean age 8 years, range 3 to 15 years) with mixed deep dermal and full thickness burn wounds were treated with Nexobrid®. The mean size of the burns was 29% TBSA. The median percentage TBSA debrided using Nexobrid® was 15% (range 2–27%). In a clinical assessment, enzymatic debridement was effective in removing dead tissue in a single application. No adverse reaction to Nexobrid® and serious complications after enzymatic procedure were recorded in the study group. The estimated relative risk of the need for reconstructive procedures decreases 3.5 times for the study group (RR 3.5, 95%CI 0.9–13.5, p = 0.089). Conclusion: The bromelain-based enzymatic method offers a good and safe debridement option to improve the treatment and life quality of children with severe burns. The main outcome of interest was the number of reconstructive procedures due to scar contractures, which was reduced in the group treated enzymatically compared to the SoC-treated children.

Silk Fibroin-Based Bioengineered Scaffold for Enabling Hemostasis and Skin Regeneration of Critical-Size Full-Thickness Heat-Induced Burn Wounds.

Millions of people around the globe are affected by full-thickness skin injuries. A delay in the healing of such injuries can lead to the formation of chronic wounds, posing several clinical and economic challenges. Current strategies for wound care aim for skin regeneration and not merely skin repair or faster wound closure. The present study aimed to develop a bioactive wound-healing matrix comprising natural biomaterial silk fibroin (SF), clinical-grade human fibrin (FIB), and human hyaluronic acid (HA), resulting in SFFIBHA for regeneration of full-thickness burn wounds. A porous, hemostatic, self-adhesive, moisture-retentive, and biomimetic scaffold that promotes healing was the expected outcome. The study validated a terminal sterilization method, suggesting the stability and translational potential of the novel scaffold. Also, the study demonstrated the regenerative abilities of scaffolds using in vitro cell culture experiments and in vivo full-thickness burn wounds of critical size (4 cm × 4 cm) in a rabbit model. Under in vitro conditions, the scaffold enhanced primary dermal fibroblast adhesion and cell proliferation with regulated extracellular matrix (ECM) synthesis. In vivo, the scaffolds promoted healing with mature epithelium coverage involving intact basal cells, superficial keratinocytes, multilayers of keratohyalin, dermal regeneration with angiogenesis, and deposition of remodeled ECM in 28 days. The relative gene expression of the IL6 marker indicated transitions from inflammation to proliferation stage. In addition, we observed skin appendages and rete peg development in the SFFIBHA-treated wound tissues. Although wound closure was observed, neither negative (untreated/sham) nor positive (commercially available product; NeuSkin) control wounds developed skin appendages/rete pegs or native skin architecture. After 56 days, healing with organized ECM production enabled the recovery of mechanical properties of skin with higher tissue maturity in SFFIBHA-treated wounds. Thus, in a single application, the SFFIBHA scaffold proved to be an efficient biomimetic matrix that can guide burn wound regeneration. The developed matrix is a suture-less, hemostatic, off-the-shelf product for potential wound regenerative applications.

Efficacy of hydrosurgical excision combined with skin grafting in the treatment of deep partial-thickness and full-thickness burns: A two-year retrospective study

IntroductionDeep partial-thickness and full-thickness burn wounds often undergo tangential excision or escharectomy to expose healthy tissue, combined with skin grafting to promote wound healing. However, conventional tangential excision with the humby knife leads to inevitable damage to the dermis while excising burn tissue due to the lack of precision. Indeed, the preservation of dermal tissue is a key factor in determining wound healing and scar quality. The precision and tissue selectivity of the Versajet Hydrosurgical System has been established for excising burn tissue while preserving dermal tissue. In this study, we retrospectively compared the efficacy of "Hydrosurgical excision combined with skin grafting" and "Conventional tangential excision combined with skin grafting" in treating deep partial-thickness and full-thickness burn wounds to demonstrate that hydrosurgery improved the treatment of deep partial-thickness and full-thickness burns. MethodsA total of 86 patients with deep partial-thickness and/or full-thickness burns with a total burn surface area (TBSA) ≤ 25% from July 2018 to July 2020 were included in this study and were divided into experimental (hydrosurgical excision combined with skin grafting, n = 43) and control (conventional tangential excision combined with skin grafting, n = 43) groups. Parameters were analyzed, including the intraoperative blood loss volume per unit area of grafted skin, surgery duration, wound healing time, skin graft survival, and the treatment costs per unit of burned area. Scar assessment was performed at 1 year with the modified Vancouver Scar Scale linked with TBSA (mVSS-TBSA). ResultNo significant difference was found in male to female ratio, age, weight, TBSA, burn depth, skin grafting area (SKA), skin grafting methods, cases treated with carbon dioxide fractional laser or incidence of inhalation injury, and the incidence of hypovolemic shock between two groups(p > 0.05). Compared with the control group, patients treated with hydrosurgical excision combined with skin grafting experienced less intraoperative blood loss volume per unit area of grafted skin (p < 0.05). The mVSS-TBSA of patients that underwent hydrosurgical excision combined with skin grafting was significantly improved in comparison to the control group (p < 0.01). No significant difference was found in surgery duration, wound healing time, skin graft survival and treatment costs per unit of burned area between the two groups (p > 0.05). ConclusionHydrosurgical excision combined with skin grafting reduced intraoperative blood loss volume per unit area of grafted skin, improved scarring 1-year after injury, and did not increase the treatment costs per unit of burned area. This technique provides a novel alternative for managing deep partial-thickness and full-thickness burn wounds.

“Out of Touch”—Recovering Sensibility after Burn Injury: A Review of the Literature

Background: Full-thickness burn injuries (FTBI) not only lead to a significant burden in multiple ways, including social life and self-esteem, but have also a tremendous impact on environmental interaction by reducing sensibility in manifold ways. On these grounds, possible ways and solutions to recover sensibility in burn wounds are essentials and should not be overlooked. Methods: A review of experimental, clinical studies and the related literature was performed with the aim to highlight post-burn nerve regeneration and discover ways for sensory re-integration to complement the therapeutic concept. Results: In human burn injuries, it has been hypothesized that grafted cells, partly multipotent stem cells, could be additionally responsible for nerve regeneration in burn wound areas. In addition, burn eschar excision, performed within a short post-burn time frame, can reduce or even avoid long-term nerve damage by reducing post-burn toxic mediator release. Various animal studies could demonstrate sensory reinnervation of different qualities in burn wounds. Post-burn scar tissue prevents, or at least decelerates, nerve reinnervation, but could be reduced by targeted mediators. Conclusion: Sensory loss is present in skin grafted areas following full-thickness burn-wound excision, thereby leading to a reduction in quality of life. In addition, various mediators might reduce or avoid nerve damage and should be considered at an early stage as part of a holistic burn-patient therapeutic approach. In addition, supportive multifaceted physical therapy strategies are essential.

Enhanced Healing Activity of Manuka Honey and Nitrofurazone Composite in Full-Thickness Burn Wounds in the Rabbit Model

Burns cause many significant changes in metabolism and inflammatory reactions, leading to poor regeneration in animals and humans. A list of medicines to treat burns is available in the market. But due to the high cost of these medicines, these are unaffordable, especially for farmers of middle-class families of Africa and Asia. Therefore, a low-cost complementary treatment has always been a topic of many researchers, and there is a dire need of time for the welfare of animals to save them. The current study was planned to scrutinize the therapeutic effects of Manuka honey and Nitrofurazone ointments on full-thickness burn wounds in the rabbit model. The healing efficacy was performed through wound contraction rate, hematological analysis, the thickness of dermis and epidermis, and collagen content percentage. Histopathology was performed after taking biopsy samples at the end of the research. Based on statistical analysis using wound healing time (days, D), the combination (MO + NT) resulted in a shorter period (27 D ± 1) than the average healing time of controlled (36 ± 2), Manuka ointment (31.33 D ± 1.52), and Nitrofurazone ointment (32 ± 1). A significant decrease in the count of red blood cell (RBC), mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) in all treatments was noticed mainly in MO + NT. Furthermore, burns induced a significant difference (p < 0.05) in the white blood cells (WBCs) count levels in the MO-treated group. While the level of platelets (PLTs) was not significantly different from the healthy control group. Histopathological assessment (epithelialization, fibrosis, and angiogenesis) of skin showed burn healing to be better in MO and MO + NT groups. In conclusion, the composite of Manuka honey with Nitrofurazone led to the faster recovery than other treatments.

Biodegradable and injectable poly(vinyl alcohol) microspheres in silk sericin-based hydrogel for the controlled release of antimicrobials: application to deep full-thickness burn wound healing

Biodegradable and injectable poly(vinyl alcohol) microspheres in silk sericin-based hydrogel for the controlled release of antimicrobials: application to deep full-thickness burn wound healing

Hippophae rhamnoides L. leaf extract diminishes oxidative stress, inflammation and ameliorates bioenergetic activation in full-thickness burn wound healing

BackgroundGlobally, burn wounds are the prominent cause of morbidity and occasionally mortality, besides psychological and financial burden to the patients and health care systems. Numerous medical complexities associated with burn injuries prompted the quest for novel, practical therapeutic healing approaches, which could potentially influence different phases of the repair process positively. PurposeThe present study investigates the influence of Seabuckthorn leaf aqueous lyophilized extract (SBTL-ALE) on full-thickness burn wounds in rats to establish its healing efficacy and to explore its possible mechanisms of action concerning molecular, cellular, and histopathological features. MethodsTransdermal burn wound created on the dorsal surface of the rat. Animals were randomly distributed into three different groups and topically treated with vehicle base (control group), 2.5% SBTL-ALE ointment (experimental group) and silver sulfadiazine cream (SSD, positive drug control group) twice daily for seven consecutive postwounding days. ResultsImmunohistochemical analyses revealed enhanced proliferation, re-epithelialization, neovascularization, dermal hydration as demonstrated by significantly up-regulated (p < 0.05) expression of PCNA, cytokeratin-14, CD31, and aquaporin3, respectively in SBTL-ALE treated group as compared with the control and SSD groups. Picrosirius red staining confirmed the deposition of well-aligned, densely-packed, mature collagen in the SBTL-ALE group. The signature markers of oxidative stress and inflammation (ROS, 3-nitrotyrosine, NOS-2, NF-κB, TNF-α, IL-1β, IL-6) were found to be significant (p < 0.05) decreased in the treated group as compared to the control. Immunoblot analysis exhibited that SBTL-ALE treatment conferred cytoprotection as evidenced by significantly (p < 0.05) up-regulated expression of GRP78, thermo-sensitive cation channel (TRPV3), and HIF-1α. Additionally, activation of energy metabolism and bioenergetics (increased hexokinase, citrate synthase, G6PD, cytochrome c oxidase, ATP, decreased LDH) was observed after SBTL-ALE treatment. ConclusionSBTL-ALE treatment confers cytoprotection, redox homeostasis, cellular proliferation, re-epithelialization, angiogenesis, and dermal hydration during repair of full-thickness burn wound healing in rats. Furthermore, its treatment attenuates oxidative stress, inflammatory responses and enhances bioenergetic activation. Taken together, SBTL-ALE topical application augments burn wound healing, which could be of high clinical significance. The leads from the present findings could serve as valuable information for further applications of SBTL-ALE in pharmaceuticals and cosmeceuticals.

Functionalized gelatin/strontium hydrogel bearing endothelial progenitor cells for accelerating angiogenesis in wound tissue regeneration.

While polymer hydrogels are frequently utilized as wound dressings, they lack the sufficient bioactivity necessary to promote re-epithelialization and angiogenesis. In this work, a therapeutic angiogenesis complex is developed using a mixture of dopamine-modified polyhedral oligomeric silsesquioxane (Dopa-POSS), strontium ions (Sr2+ ions) photocrosslinked gelatin methacryloyl (GelMA) hydrogel and endothelial progenitor cells (EPCs) for full-thickness burn wound healing. Dopa-POSS is used to reinforce the hydrogel, and Sr2+ ions stabilizer is densely incorporated inside the network of GelMA hydrogels by ultraviolet cross-linking, thus effectively enhancing the hydrogel mechanical strength. The multifunctional GelMA hydrogels comprised gelatin's arginine-glycine-aspartate (RGD) patterns and active Sr2+ ions that promote EPC biological activity and proliferation. Notably, the Sr2+ ions in the functional hydrogels substantially enhanced EPC proliferation in a three-dimensional environment, migration, and angiogenesis-related protein expression. After 14days, the Gel/Sr2+@POSS/EPCs composite hydrogel substantially accelerates and enhances the new blood vessel development process, collagen deposition, and re-epithelialization with the almost closed wounds and newly created tissue. Thus, UV-crosslinked Gel/Sr2+@POSS hydrogels functionalized with EPCs can be a potentially beneficial therapeutic system for full-thickness burn wound healing.

Controlled dual release of dihydrotestosterone and flutamide from polycaprolactone electrospun scaffolds accelerate burn wound healing.

Wound healing is a complex process involving multiple independent and overlapping sequential physiological mechanisms. In addition to cutaneous injury, a severe burn stimulates physiological derangements that induce a systemic hypermetabolic response resulting in impaired wound healing. Topical application of the anti‐androgen drug, flutamide accelerates cutaneous wound healing, whereas paradoxically systemic dihydrotestosterone (DHT) improves burn wound healing. We developed and characterized a PCL scaffold that is capable of controlled release of androgen (DHT) and anti‐androgen (F) individually or together. This study aims to investigate whether local modification of androgen actions has an impact on burn injury wound healing. In a full‐thickness burn wound healing, mouse model, DHT/F‐scaffold showed a significantly faster wound healing compared with F‐scaffold or DHT‐scaffold. Histology analysis confirmed that DHT/F‐scaffold exhibited higher re‐epithelization, cell proliferation, angiogenesis, and collagen deposition. Dual release of DHT and F from PCL scaffolds promoted cell proliferation of human keratinocytes and alters the keratinocyte cell cycle. Lastly, no adverse effects on androgen‐dependent organs, spleen and liver were observed. In conclusion, we demonstrated DHT plus F load PCL scaffolds accelerated burn wound healing when loading alone did not. These findings point to a complex role of androgens in burn wound healing and open novel therapeutic avenues for treating severe burn patients.

90 Efficacy of Porcine Skin Xenotransplants Indistinguishable from Allograft in First-in-human Clinical Evaluation

IntroductionHuman cadaver allograft (HCA) is the current standard of care for temporary wound closure of large burns, but a critical need for high-quality alternatives exists. Porcine skin shares many similarities with human skin, and hyperacute rejection is prevented via a single genetic modification. Like human skin, non-terminally sterilized porcine skin contains viable dermal and epidermal cells and intact vasculature that enables restoration of barrier function. These characteristics are distinct from those of traditional, terminally sterilized “xenografts” and may offer greater therapeutic capability. We report here key efficacy outcomes specific to severe burn care from a first-in-human clinical trial to assess the capability of genetically engineered porcine skin xenotransplants to provide temporary wound closure for severe and extensive deep-partial and full-thickness burn wounds, compared to HCA.MethodsSplit-thickness skin containing epidermal and dermal layers was harvested from Designated Pathogen Free, GalT-KO, porcine donors, cGMP processed to achieve USP< 71 > sterility and cryopreserved to retain >70% cell viability. These were transplanted side by side with HCA on debrided full-thickness burn wounds in six human subjects. Temporary wound closure, incidence of complete wound closure following autografting, and quality of healing, including scarring, contour, and feel of healed skin, normalization of skin markings or pigmentation, were independently assessed.ResultsAcross all patients and assessment time points, adherence, vascularity, and overall appearance were indistinguishable between porcine skin xenotransplants and HCA control. After surgical removal, wound beds treated with each type of dressing were perfused and otherwise appeared equivalent and clinically suitable for autografting. Long-term outcomes were comparable between wound sites treated with porcine skin or HCA with no discernable differences in scarring or cosmesis.ConclusionsSkin xenotransplants effectively provided temporary wound closure and restoration of barrier function via intact native vasculature, active cells, decreased antigenicity, and high-quality tissue architecture unimpacted by cryopreservation and thawing. These results show clinical promise as an interchangeable alternative to HCA in the treatment of severe burns. Expanded clinical evaluation is ongoing.

47 Successful Prevention of Secondary Burn Progressions Using Topical Tacrolimus and Infliximab Hydrogel

IntroductionThe pathophysiology of partial- to full-thickness burn wound conversion remains poorly understood. Recent studies have demonstrated that an altered inflammatory response may play be implicated in this secondary conversion to deeper wounds. Therefore, reduction in early inflammation may decrease burn severity and morbidity.Specifically, TNF-ɑ has been shown to detrimentally affect the healing process after injury through a variety of mechanisms. We hypothesized that microcapillary alginate hydrogel loaded with immunosuppressive medications applied to partial-thickness burns would reduce inflammation and prevent further progression to full-thickness burns.The purpose of this study was to determine whether topical application of infliximab or tacrolimus could decrease burn wound depth.MethodsAssembly of the microfluidic hydrogels was achieved by embedding microfibers within a hydrogel scaffold composed of an alginate blend. The treatment cohorts received either (1) infliximab loaded hydrogel or (2) tacrolimus skin ointment covered by hydrogel. The control cohort only received an occlusive dressing.There were 12 young (2-4 months) and 12 old ( >16 months) mice, which were separated into treatment and control cohorts. All mice were anesthetized and given partial thickness burns by a validated scalding protocol. Mice were euthanized on post-burn day 3, and skin samples were taken. Burn depth was evaluated using Vimentin immunostaining.ResultsIn young mice, infliximab hydrogel (p=.002) and tacrolimus hydrogel (p=.002) significantly decreased burn depth compared to controls. In old mice, infliximab hydrogel (p=.005) and tacrolimus hydrogel (p< .001) significantly decreased burn depth compared to controls.In young mice, infliximab and tacrolimus were similarly efficacious (p > .05). In old mice, tacrolimus significantly decreased burn depth compared to infliximab (p=.002).In controls, old mice had deeper burn wound progression than young mice (p< .001). Similarly, in those treated with infliximab, old mice had deeper burn wound progression than young mice (p=.002). Interestingly, tacrolimus was able to decrease burn wound depth in old mice such that their burn wound thickness was similar to young mice (p >.05).ConclusionsApplication of a novel microcapillary alginate hydrogel infused with infliximab or topical tacrolimus reduced partial- to full-thickness burn wound conversion in mice. Application of immunosuppressive dressings may be a promising avenue for further clinical investigation to reduce morbidity and mortality associated with burn injuries.

Assembly of skin substitute by cross-linking natural biomaterials on synthetic biodegradable porous mat for critical-size full-thickness burn wound regeneration

Human skin architecture comprises several interpenetrating macromolecules seen as organized extracellular matrix (ECM). For regeneration of critical-size acute and chronic wounds, substituting the damaged tissue with artificially assembled biomolecules offer an interactive milieu. This study reports development and preclinical evaluation of a biodegradable and immuno-compatible scaffold for regeneration of critical-size (4 × 4 cm2) full-thickness rabbit burn wounds. The designed wound care product comprises synthetic terpolymer poly(L-Lactide-co-Glycolide-co-Caprolactone) (PLGC), human clinical-grade fibrin (FIB), and hyaluronic acid (HA), termed as PLGCFIBHA. Here, clotting of fibrinogen concentrate (FC) with excess thrombin in the scaffold create an interpenetrating FIB network harnessed with adhesive molecules like fibronectin and laminin present in FC with exogenous HA to produce ECM-like milieu on porous PLGC. Penetrating into porous PLGCFIBHA, long term study showed a regulated fibroblast growth resulting in non-fibrotic dermal-like tissue in vitro. The freeze-dried PLGCFIBHA with residual thrombin facilitated suture-less, hemostatic matrix adhesion to the wound bed in vivo. By 28 d, mature and scar-less epidermis-dermis formation with skin appendages was evident in the PLGCFIBHA-treated wound area. Both negative (untreated/sham) and positive (commercial matrix-treated) control wounds showed incomplete regeneration. The PLGCFIBHA-treated wounds were comparable to native skin by 56 d. These regenerative outcomes upon single application of PLGCFIBHA confirms its potential translational value for wound care.