The impact of burn injuries on indigenous populations: A literature review.

INTRODUCTION: Ethnic minorities experience disparities in prevention and treatment of burn injury. Research focused on burn injuries in Indigenous populations is limited. This review summarizes literature on burn injuries in Indigenous populations to be considered to inform new research. METHODS: A search was conducted in CINAHL, Ovid MEDLINE, PSYCinfo and SocINDEX. for "burn OR scars OR scald OR deformity OR disfigurement" and "Aboriginal OR Indigenous OR First Nation OR American Indian OR Maori OR Native OR Torres Strait Islander OR Amerindian OR Inuit OR Metis OR Pacific Islander". Inclusion 1) peer reviewed studies of burns in Indigenous persons 2) in English. Exclusion 1) no data specific to Indigenous burns 2) not peer reviewed 3) not in full text 4) protocol publications. RESULTS: The search identified 1091 studies with 51 for review. Sixteen were excluded. The 35 included publications were published between 1987 and 2022. Findings indicated higher incidence of injury and poorer outcomes amongst Indigenous people. Indigenous people suffered more flame and inhalation burns, had longer lengths of stay, and more complications including hypertrophic scarring. Australian Indigenous patients struggle with a lack of culturally safe communication and support for aftercare. CONCLUSION: Racial disparities exist in burn injury incidence and outcome for Indigenous persons. Qualitative research in this area will help providers better understand the experiences of Indigenous burn patients to develop more culturally competent care. We are currently developing a study using qualitative hermeneutic methodology to learn about the experiences of Indigenous burn survivors' injuries, recovery, and social reintegration.

Burn mass casualty incident planning in Alberta: A case study.

Burn mass casualty incident (BMCI) preparedness is lacking across Canada. A focused exploration of the current policies, protocols and practices in Alberta that address the response to a BMCI was conducted. In this case study, data were gathered from documents outlining the health system response to a mass casualty incident and health care professionals directly involved. Interviews were conducted online, recorded and transcribed. Qualitative description was used to code common themes across documents and transcripts. Fifteen documents and nine participant interviews were included in this study. Overall, the current policies, protocols and practices in place were limited to all-hazards mass casualty incident planning and did not address the specialized needs of burn patients. Deficiencies included no burn-specific plan at each of the two burn centres, a lack of provincial-level recognition of the unique challenges associated with a BMCI and no established Canadian burn disaster communication plan. Suggestions of strategies for a burn plan included forward triage, patient movement, use of telemedicine, partnering skilled and non-skilled staff, and procuring additional supplies. For best patient outcomes the provincial health authority needs to provide dedicated time for burn care experts to develop BMCI response plans to better address this unique hazard.

Biofabrication of Cellulose-based Hydrogels for Advanced Wound Healing: A Special Emphasis on 3D Bioprinting.

Even with the current advancements in wound management, addressing most skin injuries and wounds continues to pose a significant obstacle for the healthcare industry. As a result, researchers are now focusing on creating innovative materials utilizing cellulose and its derivatives. Cellulose, the most abundant biopolymer in nature, has unique properties that make it a promising material for wound healing, such as biocompatibility, tunable physiochemical characteristics, accessibility, and low cost. 3D bioprinting technology has enabled the production of cellulose-based wound dressings with complex structures that mimic the extracellular matrix. The inclusion of bioactive molecules such as growth factors offers the ability to aid in promoting wound healing, while cellulose creates an ideal environment for controlled release of these biomolecules and moisture retention. The use of 3D bioprinted cellulose-based wound dressings has potential benefits for managing chronic wounds, burns, and painful wounds by promoting wound healing and reducing the risk of infection. This review provides an up-to-date summary of cellulose-based dressings manufactured by 3D bioprinting techniques by looking into wound healing biology, biofabrication methods, cellulose derivatives, and the existing cellulose bioinks targeted toward wound healing.

Hypertrophic Scar.

Hypertrophic scars frequently develop post-burn, and are characterized by their pruritic, painful, raised, erythematous, dyschromic, and contractile qualities. This article aims to synthesize knowledge on the clinical and molecular development, evolution, management, and measurement of hypertrophic burn scar for both patient and clinician knowledge.

Preoperative expectations, postoperative satisfaction and patient directed priorities for clinical burn research.

INTRODUCTION: Burn patients receiving split thickness skin grafting are left with scarring and chronically dysfunctional grafted skin. Given evidence that patients' preoperative expectations mediate postoperative outcomes and satisfaction, we described burn patients' experience, expectations, and satisfaction with their skin graft, their views towards a cell based clinical trial to improve their graft and identified graft outcome measures for use in future studies. METHODS: Data were collected via questionnaires preoperatively, one, and three months postoperatively. Longitudinal analyses assessed change over time. RESULTS: Expectations of graft function were consistent pre- and postoperatively. Expectations of graft appearance showed significant decrease over time (ß1 = -0.290, p = 0.008). Significant improvements in skin function (ß1 = 0.579, p = 0.000) and appearance (ß1 = 0.247, p = 0.025) at the wound site during recovery were observed. Patients noted great difference between grafted and normal skin. Patient satisfaction with their graft did not change significantly over time. Patients were willing to participate in a cell based clinical trial to improve graft symptomology and prioritized improvements in scarring, redness, sensation, and elasticity. CONCLUSIONS: Outcome measures in trials advancing skin grafting should reflect chronic, patient prioritized limitations. We recommend preoperative educational interventions for burn patients receiving grafting to improve postoperative satisfaction.

Mobile Burn Disaster Response Teams: A Scoping Review.

The resources needed to deliver modern burn care may be overwhelmed by mass casualty disasters. In 2021, the World Health Organization (WHO) recommended that countries prepare teams of deployable burn experts to assist with responding to a mass casualty disaster. The aim of this scoping review was to identify existing literature regarding burn mobile response team organization, describe the reported effectiveness of these teams, identify challenges in adopting the WHO recommendations, and consider how the recommendations may be reconsidered. We conducted a scoping review of all literature types published up to January 2022. Searches of MEDLINE, EMBASE, Scopus, and CINAHL databases were conducted to identify reports informing or reporting the use of mobile burn care specialty teams that respond to events resulting in multiple burn-injured victims, including pediatric victims and military response to civilian events. Of 6132 identified reports, 26 publications were reviewed. Three types of mobile burn response teams were identified: (1) teams organized by burn care networks, (2) government-organized medical disaster teams with burn-specific experts, and (3) the U.S. Army Burn Flight Team. Teams have responded to events such as terrorist attacks by providing specialized burn supplies and personnel. These teams have demonstrated expert triage and stabilization advantages but are limited by the number of deployable specialists. Although the WHO recommends increasing the number of mobile burn response teams available around the world, few countries have implemented this recommendation. A hybrid model where responders on scene communicate with burn center experts to manage triage may address these challenges.

Fibroblast inflammatory priming determines regenerative versus fibrotic skin repair in reindeer.

Adult mammalian skin wounds heal by forming fibrotic scars. We report that full-thickness injuries of reindeer antler skin (velvet) regenerate, whereas back skin forms fibrotic scar. Single-cell multi-omics reveal that uninjured velvet fibroblasts resemble human fetal fibroblasts, whereas back skin fibroblasts express inflammatory mediators mimicking pro-fibrotic adult human and rodent fibroblasts. Consequently, injury elicits site-specific immune responses: back skin fibroblasts amplify myeloid infiltration and maturation during repair, whereas velvet fibroblasts adopt an immunosuppressive phenotype that restricts leukocyte recruitment and hastens immune resolution. Ectopic transplantation of velvet to scar-forming back skin is initially regenerative, but progressively transitions to a fibrotic phenotype akin to the scarless fetal-to-scar-forming transition reported in humans. Skin regeneration is diminished by intensifying, or enhanced by neutralizing, these pathologic fibroblast-immune interactions. Reindeer represent a powerful comparative model for interrogating divergent wound healing outcomes, and our results nominate decoupling of fibroblast-immune interactions as a promising approach to mitigate scar.

Adult Human Dermal Progenitor Cell Transplantation Modulates the Functional Outcome of Split-Thickness Skin Xenografts.

Following full-thickness skin injuries, epithelialization of the wound is essential. The standard of care to achieve this wound "closure" in patients is autologous split-thickness skin grafting (STSG). However, patients living with STSGs report significant chronic impairments leading to functional deficiencies such as itch, altered sensation, fragility, hypertrophic scarring, and contractures. These features are attributable to the absence of functional dermis combined with the formation of disorganized fibrotic extracellular matrix. Recent work has demonstrated the existence of dermal progenitor cells (DPCs) residing within hair follicles that function to continuously regenerate mesenchymal tissue. The present work examines whether cultured DPCs could regenerate dermis within an STSG and improve overall graft function. Adult human DPCs were transplanted into a full-thickness skin wound in immune-compromised mice and closed with a human STSG. At 3 months, human DPCs (hDPCs) had successfully integrated into the xenograft and differentiated into various regionally specified phenotypes, improving both viscoelastic properties of the graft and mitigating pruritus.

Epidemiological analysis of pediatric burns in the Dominican Republic reveals a demographic profile at significant risk for electrical burns.

OBJECTIVE: Pediatric burns are preventable with legislative and infrastructural changes. Although retrospective audits of many low- and middle-income countries have aided preventative efforts, the epidemiological status of burns in the Caribbean is not known. This study characterizes pediatric burns in the Dominican Republic (DR) and compares these to age-matched North American records captured by the National Burn Repository. METHODS: A retrospective audit of 1600 patients admitted to the Unidad de Niños Quemados Dra. Thelma Rosario Hospital, the island's only major pediatric burn center, between January 2010 to March 2017 was performed. Epidemiological variables analyzed included age, gender, burn mechanism, year, month, city, admission duration, nationality, mortality, and %TBSA. RESULTS: Pediatric burn patients in the DR sustained larger burns (8.2% vs. 6.5% TBSA) and spent more days in the hospital (10 vs. 6 days). Females were overrepresented (M:F=1:1.5) and mortality amongst admitted patients was 4-fold higher (2.8% vs. 0.7%). Electrical burns were significantly overrepresented in DR (21%) compared to age-matched North American patients (2%). Although electrical burns were smaller (4% TBSA), compared to scald (14% TBSA), and flame (19% TBSA), these burns preferred hands and had a high mortality rate (3%). No significant seasonality in burn mechanisms were observed. Finally, we report geographical and age group differences in the distribution of burn mechanisms and highlight particularly vulnerable subpopulations. CONCLUSION: This investigation identifies a demographical profile where electrical burns account for a significant percentage of the burn population. This provides a basis for concentrating preventative efforts in vulnerable populations.

Burns from illegal cannabis oil manufacturing: a case series.

BACKGROUND: The increasing consideration of cannabis legalization in Canada and the United States has motivated physicians to assess its prospective impact on the health care system. Health care providers in the burns community are concerned about injuries sustained as a result of the illegal manufacturing of cannabis oil because it involves highly flammable reagents. METHODS: We report a retrospective case series of patients with cannabis oil burns (identified by evidence of combustion during cannabis oil manufacturing) treated from April 2012 to March 2014 at the Foothills Medical Centre in Calgary, Alberta, Canada. We compare the characteristics of these patients with those of patients admitted over the same period with any burns. RESULTS: We found that 12 (out of 161 patients) admitted over the review period sustained burns from cannabis oil manufacturing. Compared with patients in the total burn group, patients with cannabis oil burns were younger (75% and 48% were younger than 41 years in the group with cannabis oil burns and the total burn group, respectively), were more likely to be male (83% in the group with cannabis oil burns v. 74% in the total burn group) and sustained burns over a larger percentage of their total body surface area (24% v. 9%). Patients with cannabis oil burns also required extensive surgical management (skin grafting in 75% of cases) and spent a substantial amount of time (mean 32 d) in the burn unit. INTERPRETATION: Burns from illegal cannabis oil manufacturing are large, require extensive management and involve younger patients than burns in general. Given that the frequency of cannabis oil burns may increase in Canada after legalization, Canadian burn centres are encouraged to monitor and report on cases with this injury mechanism.

Burn clinical trials: A systematic review of registration and publications.

BACKGROUND: Randomized controlled clinical trials (CTs) are gold standard tools for assessing interventions. Although burn CTs have improved care, their status, publication frequency, and publication quality are not known. OBJECTIVES: (1) Characterize burn CTs by analyzing location, completion status, temporal trend, and funding sources. (2) Assess quality of trial reporting. DATA SOURCES: CT records were obtained from ClinicalTrials.gov and WHO's CT Registry (searched May 2017). Publications were obtained from PubMed, Google Scholar, OVID MEDLINE, and ClinicalTrials.gov (searched June 2017). PUBLICATION APPRAISAL: 23-item rubric adapted from CONSORT and ICH E3 guidelines. RESULTS: 738 burn CTs were identified globally, of which majority were publically-funded (77%), ongoing (52%), and assessed behavioral, pharmacological, device-based, dietary-based, and biological/procedural interventions. Amongst the ended trials, 69 (28%) published their findings. Significantly fewer industry-funded trials published findings (14% vs 33% publically-funded). Quality of reporting was suboptimal, and most underreported categories were trial phase, severity, and sample size estimation. LIMITATIONS: Incomplete, outdated, and non-registered CTs which are difficult to track. CONCLUSIONS: Burn trials are proliferating in number, location, and interventions assessed. Only a small proportion are published and quality of reporting is suboptimal. IMPLICATIONS OF KEY FINDINGS: Burn researchers should aim to register and report on all clinical trials regardless of outcome. Superior a priori design can reduce precocious termination and mandatory reporting of data fields can improve quality of reporting. Systematic review registration number: CRD42017068549.

Treating pain on skin graft donor sites: Review and clinical recommendations.

Split-thickness skin grafting is the most common reconstructive procedure in managing burn injuries. Harvesting split-thickness skin creates a new partial thickness wound referred to as the donor site. Pain at the donor site is reported to be one of the most distressing symptoms during the early postoperative period. Here, we (a) identify strategies for managing donor site pain, (b) assess the quality of individual studies, and (c) formulate evidence-based recommendations based on the amount and consistency of evidence. Our analysis revealed five distinct approaches to minimize donor site pain. These include: continuous subcutaneous local anesthetic infusion (three studies), subcutaneous anesthetic injection (five studies), topical agents (six studies), nonpharmacological interventions (three studies), and wound dressings (18 studies). Available randomized control trials typically evaluated pain on standardized scales (i.e. Visual Analog Scale, Numerical Rating Scale), and compared the experimental group with standard care. Recommended treatments include: (a) subcutaneous anesthetic injection of adrenaline-lidocaine; (b) ice application; (c) topical agents, such as lidocaine and bupivacaine; and (d) hydrocolloid- and polyurethane-based wound dressings accompanied with fibrin sealant. Methodologically sound randomized control trials examining the efficacy of modified tumescent solution, ropivacaine, plasma therapy, noncontact ultrasound, and morphine gels are lacking and should be a priority for future research.

Evaluating accuracy and reliability of active stereophotogrammetry using MAVIS III Wound Camera for three-dimensional assessment of hypertrophic scars.

OBJECTIVE: Current strategies for estimating positive scar volume following burns is limited to employing subjective scar scales. This study assesses the accuracy and reliability of Measurement of Area and Volume Instrument System (MAVIS) III, a portable 3D active stereophotogrammetric imaging system, for non-invasive assessment of hypertrophic scar volume and elucidates factors that leads to inaccurate volume determination. METHODS: To determine accuracy, hypertrophic scars arising in various skin and wound types were modeled using moldable putty substance. Volumetric measurements calculated by the camera's software were compared to measurements determined by fluid displacement. To assess inter-rater reliability, 25 images of patients with hypertrophic scars on various anatomical regions (hand, arm, leg, and flank area) were assessed by three blind evaluators. RESULTS: Volumetric measurements obtained from MAVIS III ranged from adequate to excellent accuracy (Pearson's correlation coefficient of 0.54-0.90) compared to measurements determined by fluid displacement. The reliability of volume determination of human hypertrophic scars was rated excellent (overall Intraclass correlation coefficient of 0.95). CONCLUSIONS: This study finds that MAVIS III is accurate in its volumetric measurements and is reliable between users; making it a potential candidate for non-invasive assessment of hypertrophic scars. Further considerations for refining active stereo-photogrammetry and the user interface of the software are also highlighted to allow superior evaluation of scar volume.

Comparison between high-frequency ultrasonography and histological assessment reveals weak correlation for measurements of scar tissue thickness.

OBJECTIVE: Current methods for evaluating scar tissue volume following burns have shortcomings. The Vancouver Burn Scar scale is subjective, leading to a high variability in assessment. Although histological assessment via punch biopsy can discriminate between the different layers of skin, such an approach is invasive, inefficient, and detrimental to patient experience and wound healing. This study investigates the accuracy of high-frequency ultrasonography, a non-invasive alternative to histology, for measuring dermal and epidermal thickness in scar tissue. METHODS: Scar thicknesses of 10 patients following burns were assessed using a 2-D high-frequency ultrasound probe. The scars were then biopsied using a circular 4mm punch biopsy for histological assessment. Dermal, epidermal, and total thickness of the scar tissue was measured using ultrasound and histology, and correlations between the two measurements were calculated. RESULTS: There was not a strong correlation between ultrasound measurement and histological analysis for epidermal, dermal, and total thickness (Spearman's rank correlation of -0.1223, -0.6242, and -0.6242) of scar tissue. CONCLUSIONS: Measurements of scar thickness using high-frequency ultrasonography did not recapitulate the in vivo dermal, epidermal and total thickness. Based on these findings, strategies for further optimization of 2-D ultrasonography is discussed before clinical and research use.

Transcriptional Analysis Reveals Evidence of Chronically Impeded ECM Turnover and Epithelium-to-Mesenchyme Transition in Scar Tissue Giving Rise to Marjolin's Ulcer.

Marjolin's ulcer (MU) is an aggressive malignancy arising within chronic wounds. A major cause is unhealed burn injuries. This results in well-differentiated squamous cell carcinoma (SCC). This study aimed to elucidate transcriptional changes leading to malignancy by investigating differentially expressed genes in squamous cells present in a SCC compared with MU. MU tumor cells were isolated from histologically confirmed biopsy of SCC within an unhealed burn scar. Epithelial cells (ECs) adjacent to the tumor were co-isolated and a SCC cell line was commercially purchased. mRNA from all three samples was isolated and its expression was quantified using RNASeq. A threshold of log2fold change >2-fold in either direction was considered "differentially expressed." Gene expression analysis revealed distinct differences in gene expression in MU cells compared with EC (665 genes), EC and SCC (1673 genes). Enrichment analysis confirmed that pathways most affected included 1) elevation of genes associated with extracellular matrix organization/degradation, 2) activation of DNA damage, and 3) activation of cytokine signaling. Our analysis revealed two key insights about chronic wound microenvironment conducive to ulceration. First, in EC vs. MU comparison, downregulation of Collagen and Matrix metalloproteinase families suggests chronically impaired extracellular matrix turnover giving rise to a fibrotic microenvironment. Second, in SCC vs. MU comparison, dysregulation of cadherin-mediated cell-cell adhesions is suggestive of epithelial-to-mesenchymal transitions, similar to those during development. Acquisition of epithelial-to-mesenchymal transition may underlie the high metastatic rate in MU tumors. Taken together, this sheds light on mechanisms that underlie the divergent clinical features of these cutaneous cancers.

Firefighter willingness to participate in a stem cell clinical trial for burns: A mixed methods study.

Adult stem cells represent a potentially renewable and autologous source of cells to regenerate skin and improve wound healing. Firefighters are at risk of sustaining a burn and potentially benefiting from a split thickness skin graft (STSG). This mixed methods study examined firefighter willingness to participate in a future stem cell clinical trial, outcome priorities and factors associated with this decision. METHODS: A sequential explanatory mixed methods design was used. The quantitative phase (online questionnaire) was followed by the qualitative phase (semi-structured interviews). A sample of 149 firefighters completed the online survey, and a purposeful sample of 15 firefighters was interviewed. RESULTS: A majority (74%) reported they would participate in a future stem cell clinical trial if they experienced burn benefiting from STSG. Hypothetical concerns related to receiving a STSG were pain, itch, scarring/redness and skin durability. Participants indicated willingness to undergo stem cell therapy if the risk of no improvement was 43% or less. Risk tolerance was predicted by perceived social support and having children. Interviews revealed four main themes: a desire to help others, improving clinical outcomes, trusting relationships, and a belief in scientific investigation. Many participants admitted lacking sufficient knowledge to make an informed decision regarding stem cell therapies. CONCLUSIONS: Firefighters indicated they were largely willing to participate in a stem cell clinical trial but also indicated a lack of knowledge upon which to make a decision. Public education of the role of stem cells in STSG will be increasingly important as clinical trials are developed.

Collagen structural alterations contribute to stiffening of tissue after split-thickness skin grafting.

The gold standard treatment for full thickness injuries of the skin is autologous split-thickness skin grafting. This involves harvesting the epidermis and superficial dermis from healthy skin and transplanting it onto the prepared wound bed. The donor site regenerates spontaneously, but the appendages and cellular components from the dermal layer are excluded from the graft. As a result, the new tissue is inferior; the healed graft site is dry/itchy, has decreased elasticity, increased fragility, and altered sensory function. Because this dermal layer is composed of collagen and other extracellular matrix proteins, the aim was to characterize the changes in the dermal collagen after split thickness grafting that could contribute to a deficit in functionality. This will serve as a baseline for future studies designed to improve skin function using pharmacological or cell-based therapies for skin repair. A xenograft model whereby human split-thickness grafts were implanted into full-thickness defects on immunocompromised (athymic Nu/Nu) mice was used. The grafts were harvested 4 and 8 weeks later. The collagen microstructure was assessed with second harmonic generation with dual-photon microscopy and light polarization analysis. Collagen fiber stiffness and engagement stretch were estimated by fitting the results of biaxial mechanical tensile tests to a histo-mechanical constitutive model. The stiffness of the collagen fibril-proteoglycan complex increased from 682 ± 226 kPa/sr to 1016 ± 324 kPa/sr between 4 and 8 weeks postgrafting. At the microstructural level there were significant decreases in both thickness of collagen fibers (3.60 ± 0.34 µm vs. 2.10 ± 0.27 µm) and waviness ratio (2.04 ± 0.17 vs. 1.43 ± 0.08) of the collagen fibers postgrafting. The decrease of the macroscopic engagement stretch from 1.19 ± 0.11 to 1.09 ± 0.08 over time postgrafting mirrored the decrease in waviness measured at the microscopic level. This suggested that the integrity of the collagen fibers was compromised and contributed to the functional deficit of the skin postgrafting.

Measurement of change in the mechanical properties of burned skin to therapist intervention with a vacuum device.

INTRODUCTION: The currently available clinical scales used to describe healed burn wounds have limitations. Quantitative measurement of the outcomes from burn therapy treatment would be useful in planning clinical care, resource allocation and research. The purpose of this study was to observe the measurements of a portable materials testing device before and after burn therapist intervention for closed burns. METHODS: A recording was taken using a hand-held vacuum device to measure deformation of the skin in the same location prior to and following a treatment session with a burn therapist in an outpatient clinic at a tertiary burn center. RESULTS: Twenty-eight subjects were recruited to the study. Statistically significant differences were noted in modulus and elasticity change between sheet and meshed split thickness autografts (p=0.0233). Positive change in modulus was correlated with increasing therapy time (R=0.46), specifically for meshed grafts (R=0.70). Positive change in modulus was noted in therapy time greater than 48 min. CONCLUSIONS: Quantitative measurement of the outcomes of burn therapies on the mechanical properties of healed burns is possible in an outpatient clinic setting. Improvement in the stiffness of burn scars was observed in treatment sessions that last at least 48 min.

Response of human skin to esthetic scarification.

This study was undertaken to investigate changes in RNA expression in previously healthy adult human skin following thermal injury induced by contact with hot metal that was undertaken as part of esthetic scarification, a body modification practice. Subjects were recruited to have pre-injury skin and serial wound biopsies performed. 4 mm punch biopsies were taken prior to branding and 1 h, 1 week, and 1, 2 and 3 months after injury. RNA was extracted and quality assured prior to the use of a whole-genome based bead array platform to describe expression changes in the samples using the pre-injury skin as a comparator. Analysis of the array data was performed using k-means clustering and a hypergeometric probability distribution without replacement and corrections for multiple comparisons were done. Confirmatory q-PCR was performed. Using a k of 10, several clusters of genes were shown to co-cluster together based on Gene Ontology classification with probabilities unlikely to occur by chance alone. OF particular interest were clusters relating to cell cycle, proteinaceous extracellular matrix and keratinization. Given the consistent expression changes at 1 week following injury in the cell cycle cluster, there is an opportunity to intervene early following burn injury to influence scar development.