Comparison of Efficacy among Three Dermal Substitutes in the Management of Critical Lower-Limb Wounds: The Largest Biases-Reduced Single-Center Retrospective Cohort Study in Literature

Background and objectives: The skin recently became the main focus of regenerative medicine and, in this context, skin substitutes are fully entering into the plastic surgeon’s armamentarium. Among the various types of skin substitutes, dermal substitutes (DSs) are the most used. Our study aims to retrospectively compare three renowned and extremely similar DS in the management of critical lower limb wounds in the largest cohort analysis currently present in literature. Materials and Methods: We followed a strict protocol of application and evaluation of the DS for each patient and wound and, after a meticulous bias reduction process, we compared final outcomes in terms of efficacy and speed in achieving the defect coverage. Results: Among patients who did not receive a skin graft after the DS, we registered a wound healed surface of 50% for Pelnac, 52% for Integra, and 19% for Nevelia, after 30 days from the external silicon layer removal; among those who received a skin graft after the DS, we observed a significantly lower mean percentage of graft take after 7 days with Pelnac (53%) compared to Integra and Nevelia (92% and 80%, respectively). The overall percentage of wound healed surface obtained after 30 days from the external silicon sheet removal, either with or without skin graft, was 71% for Pelnac, 63% for Integra and 63% for Nevelia. We also ran a sub-group analysis only including grafted wounds with a negative microbiological test and the mean percentage of graft take was similar this time. Eventually, we assessed the influence of the wound’s “chronicity” on its healing, comparing the mean graft take only in “acute” wounds who received a skin graft and it resulted 63% for Pelnac, 91% for Integra and 75% for Nevelia. Conclusions: Integra demonstrates the highest rate of skin graft viability and the highest rate of skin graft takes after 7 days. Pelnac shows the quickest induction of secondary healing in acute wounds. Nevelia is not different from Integra and shows a superior graft take compared to Pelnac, but features the lowest secondary healing induction rate. No differences exist between the three DSs in terms of wound healing after 30 days from the skin graft or from the removal of the external silicon layer.

Usage of Dermal Substitutes for Hand Coverage and Reconstruction

Background Hand coverage and reconstruction gives a challenge for plastic surgery. In this study we introduce a method for hand coverage and reconstruction by dermal substitutes which easy and simple to use. Objectives The aim of this study is to know the versatility of dermal substitutes in reconstruction & coverage of complex hand defects. Patients and Methods This was a cohort study conducted on 20 patients with hand tissue loss; to evaluate the versatility of dermal substitutes in reconstruction & coverage of complex hand defects. Patients attending El Helmeia armed forces hospital (plastic and reconstructive department) & Ain shams university hospital with follow up duration up to 6 months. All patients had clean wound & complex hand defects with exposed tendon and/or bone, Defects post trauma and after tumour excision and Post burn hypertrophic scars, keloid or contractures. Results We found that; the mean age of all patients was (23.5 ± 8.82) years. Regarding gender of the patients, the majority (80%) of patients were males; while (20%) were females. Regarding side of raw area; (55%) of patients had Rt-sided raw area, and (45%) had Lt-sided raw area. Regarding site of raw area; (20%) of patients had Finger-tip raw area, (20%) had Palm raw area, (10%) had Volar surface of little and ring raw area, (10%) had Volar surface of little finger raw area, (25%) had Dorsum raw area, (10%) had Dorsum of lateral 4 fingers raw area, while (5%) had Dorsum of middle finger raw area. Regarding Etiology of raw area; (70%) of raw areas caused by Trauma, (15%) caused after burn keloid removal, (10%) caused after burn contracture, and (5%) caused by donor site. Regarding Intervention data; (50%) of patients used Integra dermal substitute; and (50%) used Pelnac dermal substitute. Regarding follow up data; the average Time of removal was (3.65 ± 0.49) weeks, and the average Time for follow up was (3.25 ± 1.12) months. Comparative study between 20 hand tissue loss patients revealed; highly significant increase in Post-operative STSG satisfaction rate (70%); with highly significant statistical difference (p < 0.01), highly significant increase in Post-operative STSG good movement (80%); with highly significant statistical difference (p < 0.01). Conclusion The use of dermal substitutes cons gives an alternative reconstructive option for managing extended skin avulsion injuries of the upper extremity; it reduces postoperative immobilization, minimizes donor site morbidity and provides good functional and esthetic results in a single surgical procedure.

Keratin-Alginate Sponges Support Healing of Partial-Thickness Burns

Deep partial-thickness burns damage most of the dermis and can cause severe pain, scarring, and mortality if left untreated. This study serves to evaluate the effectiveness of crosslinked keratin–alginate composite sponges as dermal substitutes for deep partial-thickness burns. Crosslinked keratin–alginate sponges were tested for the ability to support human dermal fibroblasts in vitro and to support the closure and healing of partial-thickness burn wounds in Sus scrofa pigs. Keratin–alginate composite sponges supported the enhanced proliferation of human dermal fibroblasts compared to alginate-only sponges and exhibited decreased contraction in vitro when compared to keratin only sponges. As dermal substitutes in vivo, the sponges supported the expression of keratin 14, alpha-smooth muscle actin, and collagen IV within wound sites, comparable to collagen sponges. Keratin–alginate composite sponges supported the regeneration of basement membranes in the wounds more than in collagen-treated wounds and non-grafted controls, suggesting the subsequent development of pathological scar tissues may be minimized. Results from this study indicate that crosslinked keratin–alginate sponges are suitable alternative dermal substitutes for clinical applications in wound healing and skin regeneration.

Assessment of Financial Conflicts of Interest Related to the Use of Dermal Substitutes in Burn Management

This study aims to systematically review the accuracy of the self-reporting of conflicts of interest (COI) among studies related to the use of dermal substitute products in burn management and evaluate factors associated with increased discrepancies. To do so, a literature search was done to identify studies investigating the use of dermal substitutes in burn management published between 2015 – 2019. Industry payments were collected using the Centers for Medicare & Medicaid Services Open Payments database. Declared COI were then compared with the listed payments. Studies and authors were considered to have a COI if they received payments totaling >$100 for each company. A total of 51 studies (322 authors) were included for analysis. Thirty-eight studies (75%) had at least one author received an undisclosed payment from industry. From 2015 to 2019, 1391 general payments (totaling $1,696,848) and 108 research payments (totaling $1,849,537) were made by 82 companies. When increasing the threshold on what would be considered an undisclosed payment, the proportion of authors with discrepancies gradually decreased, from 88% of authors with undisclosed payments >$100 to 27% of authors with undisclosed payments >$10,000. Author order, journal impact factor, and study type were not significantly associated with increased risk of discrepancy. We found that the majority of studies investigating the use of dermal substitute products for burn management did not accurately declare COI, highlighting the need for a uniform declaration process and greater transparency of industry sponsorship by authors when publishing peer-reviewed burn surgery research papers.

Cyclic Adenosine Monophosphate Eliminates Sex Differences in Estradiol-Induced Elastin Production from Engineered Dermal Substitutes

Lack of adult cells’ ability to produce sufficient amounts of elastin and assemble functional elastic fibers is an issue for creating skin substitutes that closely match native skin properties. The effects of female sex hormones, primarily estrogen, have been studied due to the known effects on elastin post-menopause, thus have primarily included older mostly female populations. In this study, we examined the effects of female sex hormones on the synthesis of elastin by female and male human dermal fibroblasts in engineered dermal substitutes. Differences between the sexes were observed with 17β-estradiol treatment alone stimulating elastin synthesis in female substitutes but not male. TGF-β levels were significantly higher in male dermal substitutes than female dermal substitutes and the levels did not change with 17β-estradiol treatment. The male dermal substitutes had a 1.5-fold increase in cAMP concentration in the presence of 17β-estradiol compared to no hormone controls, while cAMP concentrations remained constant in the female substitutes. When cAMP was added in addition to 17β-estradiol and progesterone in the culture medium, the sex differences were eliminated, and elastin synthesis was upregulated by 2-fold in both male and female dermal substitutes. These conditions alone did not result in functionally significant amounts of elastin or complete elastic fibers. The findings presented provide insights into differences between male and female cells in response to female sex steroid hormones and the involvement of the cAMP pathway in elastin synthesis. Further explorations into the signaling pathways may identify better targets to promote elastic fiber synthesis in skin substitutes.

657 Bilayer Dermal Substitute in Management of Deep Hand Burns

Introduction Bilayer dermal substitutes, composed of bovine collagen cross-linked with glycosaminoglycan and silicone, have become increasingly integrated into the algorithm for management of complex burns. In complex hand burns, dermal substitutes improve functional and aesthetic outcomes while also allowing early excision in high percentage TBSA burns. We detail the outcomes of 17 patients with 25 cases of complex hand burns managed at our center using a staged procedure of cadaveric allografting followed by dermal substitute placement and early definitive STSG. Methods Between Jan 2018 and Aug 2019, all patients who sustained deep partial/full thickness burns to their hands managed with dermal substitution were identified. Patients less than 18 yo, with additional non-burn trauma to the hands, and with initial operative management at another center prior to transfer were excluded. A retrospective chart review was used to collect data regarding time to operative excision, placement of allografts and substitutes, definitive STSG, and functional outcome. Results 17 patients from 18 and 89 yo presented with 25 deep partial/full thickness hand burns. TBSA varied from 0.75 to 78% (mean 17.7%). On average, patients underwent first excision 5.3 (2–16) days after initial burn or 4.2 days after presentation. Our protocol often uses allografting prior to placement of the dermal substitute, therefore, 22 of 25 burned hands received cadaver allografts at initial excision. Dermal substitute was placed an average of 9.2 days later. 3 of 25 burns had immediate application of dermal substitute at first excision. Following substitute, non-meshed, split-thickness autografts were placed on 18 hands. 5 of the burns did not require STSG and two hands were not further evaluated due to loss of patient follow-up. Of the 25 cases, all had near complete incorporation of the substitute without need for revision. In follow-up, patients who did not require STSG have shown no major limitations in ROM/scarring. Of those who underwent STSG, 6 hands underwent contracture release, with 2 of these progressing to amputation. One hand required repeat autografting due to graft loss. All remaining 18 hands healed well with near complete graft take and minimal scarring or functional limitation. Conclusions Dermal substitutes assist in the closure of complex deep hand burns. Cadaveric allografting prior to placement of the substitute ensures an appropriately excised wound base, allowing for near complete integration without need for reapplication. Autografting following dermal substitution placement may be initiated earlier than previously pursued and occasionally allows for healing without STSG.