A Comparative Analysis of the Outcomes of Various Graft Types in Burn Reconstruction Over the Past 24 Years: A Systematic Review

Burn injuries, a major global health concern, result in an estimated 180,000 fatalities annually. Despite tremendous progress in treatment methods over the years, the morbidity and mortality associated with burns remain significant. Autologous skin grafting, particularly split-thickness skin grafting (STSG), has been a cornerstone in burn reconstruction, and it has facilitated survival and functional recovery for total body surface area (TBSA) significantly. However, the requirement for primary closure at the donor site due to the constraints of full-thickness donor harvesting continues to pose challenges. The introduction of dermal regenerative templates (DRT) in the late 1970s marked a substantial step forward in tissue engineering, addressing the inadequacy of dermal replacement with STSGs. This systematic review aimed to compare the outcomes of different graft types - bioengineered, autografts, allografts, and xenografts - in burn reconstruction over the last 24 years. The review focused on the pros and cons of each graft type, offering clinical insights grounded in experience and evidence. The approach involved a systematic review of studies published in English from January 2000 to January 2024, covering randomized controlled trials (RCTs), cohort studies, case-control studies, and case series. The participants comprised individuals of all ages who underwent burn reconstruction with skin grafts, specifically split-thickness grafts, full-thickness grafts, composite grafts, and epidermal grafts (autografts, allografts, and xenografts) and bioengineered grafts. The primary outcomes were functional and cosmetic results, patient satisfaction, graft survival, and complications. The risk of bias was evaluated using the Cochrane risk-of-bias tool for randomized trials version 2 (RoB 2), the Newcastle-Ottawa Scale (NOS) for non-randomized studies, and the Canada Institute for Health Economics (IHE) quality appraisal tool for case series. Our initial search yielded a total of 1,995 articles, out of which 10 studies were selected for final analysis. Among the four clinical trials assessed, 75% showed a high risk of bias. The studies reviewed involved various graft types, with six studies (60%) concentrating on allografts, three (30%) on autografts, and one (10%) on bioengineered skin grafts. The outcomes were varied, underlining the intricate nature of burn wound management. Our evaluation revealed promising results for autologous-engineered skin substitutes and allografts but also highlighted methodological disparities among the studies included. The dominance of observational studies and the diversity of outcome measures present obstacles to direct comparisons. Future research should address these limitations, employing well-structured RCTs, standardized outcome measures, and exploring long-term outcomes and patient-specific factors. The rapidly evolving field of regenerative medicine offers great potential for novel grafting methods. This systematic review provides valuable insights into the diverse outcomes of burn reconstruction using different graft types. Autologous-engineered skin substitutes and allografts seem to hold significant promise, suggesting a possible shift in grafting techniques. However, methodological inconsistencies and the lack of high-quality evidence underscore the necessity for further research to fine-tune burn care approaches.


Introduction And Background
Burn injuries are a significant health concern worldwide, often leading to substantial morbidity and mortality; an estimated 180,000 deaths are caused by burns every year [1][2][3].In 2008, over 410,000 burn injuries occurred in the United States of America, with approximately 40,000 requiring hospitalizations [3].Over time, the treatment of these injuries has witnessed significant improvement, mainly due to the development of various grafts.The current gold standard for treating major burns is autologous skin grafting, enabling survival and functional restoration in burn injuries by covering increasingly larger total body surface areas (TBSA) [1].
Several types of skin grafts are used in medical procedures.Split-thickness grafts involve removing the top layer of the skin (epidermis) and a portion of the deeper layer (dermis).These grafts are typically harvested from the front or outer thigh, abdomen, buttocks, or back [4].Full-thickness grafts remove the epidermis and dermis completely from the donor site, typically the abdomen, groin, forearm, or area above the collarbone.These grafts are often used for minor, highly visible wounds, such as those on the face [4].Composite grafts contain skin and other tissues, such as cartilage or blood vessels, and are often used when the area to be covered needs more than just skin.Epidermal grafts, which only involve the epidermis, are less common than split-thickness and full-thickness grafts [5].Grafts can also be classified based on their origin.Autografts are taken from the patient's own body.Allografts are taken from another person.Xenografts are taken from another species, typically pigs [6].Synthetic skin substitutes constitute manufactured products that function as skin equivalents [6].
Autologous skin grafting has been a lifesaver in the field of burn care [1].However, the objective of replacing damaged skin with similar skin structures is often unachievable since full-thickness donor harvesting necessitates primary closure at the donor site for healing.In contrast, split-thickness skin grafting (STSG) only takes a portion of the dermis from the donor site, allowing it to re-epithelialize independently; patients with large defects or more surface to cover will require an allograft [1].Consequently, STSG is now the main method of wound closure for major burns globally [1].
The creation of the first dermal regenerative template (DRT) in the late 1970s marked a significant breakthrough in tissue engineering.It tackles the problem of inadequate dermal replacement when STSGs are used on full-thickness defects [1].Despite its advantages, the use of flaps is often restricted in burn patients due to various reasons [2].This review will offer a comparative analysis of the outcomes of different graft types (autografts, allografts, and xenografts) in burn reconstruction, highlighting the primary advantages and drawbacks of each product and providing practical insights based on clinical experience and evidence.The goal of this systematic review is to compare the outcomes of different graft types in burn reconstruction over time.

Review Methods
The current study adhered to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and employed research grounded in evidence to carry out an exhaustive systematic review [7,8].

Search Strategy
Criteria for inclusion and exclusion were employed to carefully select only studies of high caliber for our analysis.We applied a stringent exclusion criterion to guarantee that the studies incorporated in our analysis were not only of high quality but also pertinent to our research objectives.On 01/04/2024, we initiated a comprehensive search across three major databases: PubMed (Table 1), ScienceDirect (Table 2), and Cochrane (Table 3).Our search strategy involved the use of Medical Subject Heading (MeSH) terms, Boolean operators, and free text terms to ensure a wide coverage of relevant studies.

Search terms Results
("Skin

Inclusion and Exclusion Criteria
Types of study: We searched for pertinent studies published in English from January 2000 to January 2024.We thoroughly examined randomized controlled trials (RCTs), cohort studies, case-control studies, and case series.We ruled out systematic reviews, meta-analyses, narrative reviews, and most of the studies that are observational or at the bottom of the hierarchy of scientific evidence.Additionally, we discarded studies that failed to provide a lucid description of their procedures, duplicates, and those from which we could not procure the necessary data, those complete texts we could not view, or those from whose original author we did not receive a response via email.
Types of participants: Our study established specific selection criteria for participants, which were as follows: articles with patients of any age who had undergone burn reconstruction in the form of a skin graft, including articles that only report the type of skin graft, such as STSG, full-thickness grafts, composite grafts, and epidermal grafts (autografts, allografts, and xenografts), and bioengineered graft.We excluded studies involving any type of treatment other than a skin graft, studies involving animals or in vitro models, studies involving patients who had not undergone burn reconstruction, or those where the burn reconstruction did not involve grafting.We aimed to include a diverse range of participants to gain a more comprehensive understanding of the intervention.
Types of intervention: Interventions involving any type of graft used in burn reconstruction such as autologous skin grafting, DRT, perforator-based interposition flaps, full-thickness skin grafts, and bioengineered grafts from any origin, such as autologous, xenograft, and allografts.The control group could involve those without any intervention, those involving standard care, or alternative intervention studies that did not involve a graft or where the type of graft used is not clearly specified.
Outcomes: The outcome measures included studies that reported on the outcomes of burn reconstruction with different graft types; this could include functional outcomes, cosmetic outcomes, patient satisfaction, graft survival, and complications.We excluded studies that did not report outcomes or where the outcomes were not clearly defined.

Data Extraction
Selection of studies: After an initial review based on the titles and abstracts, two reviewers (JLC, KAP) independently chose trials to be included in this review, guided by pre-established inclusion and exclusion criteria.The Rayyan web app [9] was utilized in this search to extract pertinent data, and duplicate entries were removed.Keywords were used to aid with the search [9].Any disagreements regarding the inclusion of studies were settled through consensus and consultation with a third author (JRFV).For the full-text screening, two reviewers (JLC, KAP) independently picked trials for inclusion, again using predetermined inclusion and exclusion criteria.This search was conducted using Rayyan [9] (to extract relevant data, and duplicates were filtered out; keywords were used) [9].Disagreements about the inclusion of studies were again resolved through consensus and consultation with a third review author (JRFV).

Data Evaluation
Assessment of risk of bias in included studies: We performed the data evaluation by using the standards outlined in Cochrane.To gauge the quality of the studies included, we utilized the Cochrane RoB 2.0 tool [10], which scrutinizes potential bias in RCTs.For case-control and cohort studies, we applied the Newcastle-Ottawa Scale (NOS) [11].Finally, for case series, we used the Canada Institute for Health and Economics (IHE) quality appraisal tool [12].
Two independent reviewers (FJMD, MMQ) assessed the risk of bias in each study, taking into account the specific criteria and guidelines provided by the respective tools.Any disagreements between the reviewers were resolved through discussion or, if necessary, by consulting with a third, blinded reviewer.The methodological components of the trials and case-control, cohorts and case series were "a low, high, or unclear risk of bias" according to the Cochrane Handbook for Systematic Reviews of Interventions, NOS, and IHE guidelines, respectively [11][12][13].

Results
The process of identifying and selecting studies from the database resulted in a shortlist of 1,995 articles.Upon careful scrutiny, 543 duplicate articles were removed.The initial screening of titles and abstracts led to the selection of 32 publications for a more detailed review, which involved accessing the full texts.After assessing the suitability and quality of these shortlisted full-text papers, 10 articles were chosen for the final review process.The procedure for selecting the studies is illustrated in the PRISMA flow chart in Figure 1.

FIGURE 1: PRISMA flow chart
The flow diagram, which is based on the PRISMA statement [7], outlines our process.We initially identified 1,995 articles from three separate databases.Out of these, 42 were retrieved, and 32 were evaluated for their suitability.Finally, we included 10 articles in this systematic review after a thorough assessment PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses Of the four clinical trials evaluated, 0 (0%) showed an overall low risk of bias, one (25%) showed some concern for bias, and three (75%) had a high risk for bias.Of the one study evaluated using NOS, one (100%) showed good quality (Figures 2-3, Table 4).The appraisal for the case reports and case series is depicted in Table 5.

FIGURE 2: Risk of bias assessment for randomized controlled studies
The evaluation was carried out using the Cochrane risk-of-bias tool for randomized trials [10].Each article was assessed for bias risk.Of the four articles evaluated, three exhibited a high risk of overall bias [14][15][16].In comparison, one article showed some concern for bias [17]

FIGURE 3: Traffic light plot for randomized controlled trials
This figure shows part of the risk of bias, and the overall results are depicted with three colors: green (low risk), yellow (some concerns), and red (high risk) [

TABLE 5: Risk of bias assessment for case reports and case series
This table presents a risk of bias assessment for case reports and case series from four different studies cited above.We employed the appraisal tool by The Canada Institute of Health Economics (IHE) [12].The assessment was based on a set of leading explanatory questions across various domains such as "study objective, study design, study population, intervention and co-intervention, outcomes measures, statistical analysis, results and conclusions, and competing interests and sources of support".The responses to these questions were categorized as "Yes," "No," or "Unclear" for each study Of the 10 studies examined, six (60%) used allografts or allogenic skin grafts in the burn reconstruction process, three used autograft skin grafts (30%), and only one used the bioengineered skin graft (10%).These studies explored various factors such as the degree of burn, sample size, intervention methods (such as allogenic, autograft, and bioengineered), controls, and reconstruction techniques (such as split-thickness skin graft and dermal graft).The goal was to gain valuable insights into burn wound management by assessing aspects like scar flexibility, blood supply, and sensory outcomes.The results highlighted that treating burns involves many different aspects.
For example, Pfister et al. [14] conducted an RCT involving 30 participants, focusing on allogenic and autologous skin grafts using the STSG technique.The research indicated the potential advantages of autologous-engineered skin substitutes over split-thickness skin autografts, such as the reduced need for donor skin and lower mortality rates.Conversely, Moravvej et al.'s case series [20] of 14 patients with thirddegree burns showed faster healing and less scar formation with alloskin grafting compared to petroleum jelly-impregnated gauze.These results collectively highlight the variety of methods used in burn treatment and underscore the necessity for additional research and clinical trials to determine the efficacy and feasibility of different graft types and techniques.The studies acknowledged their limitations such as those related to sample size, absence of randomization, and the requirement for longer follow-up periods, singling out areas for future exploration in burn care.More results are shown in Table 6.However, the difference in scar formation became insignificant after 12 months, and no differences were observed between the two groups after a one-year follow-up.This suggests that the longterm outcomes of both treatments may be similar  These findings led us to conclude that the best practice for burn reconstruction is to promptly remove the damaged tissue and close the wound using one of the traditional methods, such as autograft.

Discussion
This systematic review shed light on the varied outcomes of burn reconstruction with different graft types.Despite methodological differences across the 10 studies, certain palpable trends emerged.Autologousengineered skin substitutes showed potential benefits over traditional autografts, including a reduced need for donor skin and lower mortality rates.Allografts, especially alloskin grafting, offered faster healing and less scarring compared to petroleum jelly-impregnated gauze.Bioengineered skin grafts, though limited to one study, suggested less morbidity and better long-term recovery for extensive, full-thickness burns.
These findings echo previous research supporting the superiority of autologous grafts in certain situations.
The potential advantages of autologous engineered skin substitutes could lead to a shift in grafting techniques, thereby reducing donor site morbidity and improving patient outcomes [15].Allografts, particularly alloskin, could provide a valuable alternative for burn treatment, underscoring the need to explore different graft types based on patient characteristics and burn severity.The results also highlight the importance of innovative approaches, like bioengineered skin substitutes, in enhancing burn care outcomes.
This review has a few limitations, including the heterogeneity of study designs, patient populations, and outcome measures, making direct comparisons challenging.The predominance of observational studies and the lack of high-quality RCTs could introduce biases.The evaluated studies showed varying bias risks, emphasizing the need for further high-quality research to strengthen the evidence base in the field of burn reconstruction.Future research should address these limitations and enhance our understanding of burn reconstruction outcomes.We recommend further well-designed, multicenter, RCTs comparing different graft types, employing standardized outcome measures, and addressing patient population variability.
Exploring the long-term outcomes of different graft types and investigating the impact of patient-specific factors on graft success would help refine burn care strategies.Future research should focus on developing novel grafting techniques and materials, considering the evolving field of regenerative medicine.Bioengineered skin substitutes, as demonstrated in the study by Boyce et al., show significant promise.

Conclusions
The systematic review of 10 studies revealed a diverse range of outcomes in burn reconstruction with various graft types.Autologous engineered skin substitutes and allografts, particularly alloskin grafting, demonstrated great potential for positive outcomes over traditional methods.These findings suggest an emerging shift in grafting techniques that could enhance patient outcomes and reduce donor site morbidity.However, the heterogeneity of study designs and patient populations and the predominance of observational studies underscores the need for further high-quality multicenter RCTs.Future research should focus on comparing different autologous-engineered skin substitutes, exploring long-term outcomes, and investigating the impact of patient-specific factors on graft success.The evolving field of regenerative medicine also presents opportunities for developing novel grafting techniques and materials.While our review provides valuable insights into burn reconstruction outcomes, it also highlights the complexities of this field and the need for further research to refine burn care strategies with techniques such as autologousengineered skin substitutes.
contribute valuable insights to the field of burn wound management and might pave the way for more widespread use of biological dressings like AMs in clinical practice.However, the results of the study would need to be evaluated upon completion of 13.5 months post-surgery, pliability was significantly enhanced in FTSG compared with SSG.Vascularity and height of SSGs were preferred, though not statistically significant.No difference in sensation between the two types of graft or donor site outcomes.Hair growth was significantly more prominent in FTSG.Equal number of contractures in both groups, with grafts involving both palms and digits more commonly affected The study indicates that FTSG can lead to improved outcomes, especially in scar pliability in children with deep palm burns.However, hair growth is a cosmetic concern associated with FTSG.The study acknowledges its limitations, including the lack of randomization, small sample size, and the need for more long-term follow-up.To address these limitations, the study suggests conducting a multicenter, that alloskin had better properties than petroleum jelly-impregnated gauze for burn treatment.The healing time was significantly shorter in the alloskin group (8.8 days) compared to the petroleum jelly group (13.6 days).Alloskin also resulted in less scar formation and a pigmentation score closer to normal.

TABLE 2 : ScienceDirect search
Specific search string used to identify relevant articles on the ScienceDirect database.Search and extraction date: 01/04/2023

TABLE 3 : Cochrane search
Specific search string used to identify relevant articles on Cochrane Library.Search and extraction date: 01/04/2024

TABLE 4 : Risk of bias assessment with the Newcastle-Ottawa Scale for non-randomized studies
Good quality: 3 or 4 stars in the selection domain AND 1 or 2 stars in the comparability domain AND 2 or 3 stars in the outcome/exposure domain.Fair quality: 2 stars in the selection domain AND 1 or 2 stars in the comparability domain AND 2 or 3 stars in the outcome/exposure domain.Poor quality: 0 or 1 star in the selection domain OR 0 stars in the comparability domain OR 0 or 1 star in the outcome/exposure domain 2024 Aleman Paredes et al.Cureus 16(2): e54277.DOI 10.7759/cureus.542776 of 12