Despite extensive prevention programs, burns remain a frequent cause of injury in Switzerland with a known age peak in children. Pediatric burns may cause substantial morbidity, a psyochological burden and therapy related high economic costs. To improve preventive measures, precise knowledge of etiology and treatment of pediatric burns in Switzerland as well as their temporal evolution is indispensable. The present retrospective analysis included pediatric burn patients admitted for acute treatment to the Pediatric Burn Center of the University Children`s Hospital Zurich over the last four decades. Sociodemographic, injury related, and treatment related data were extracted from medical records. Linear regression analysis was applied to determine temporal changes during the past four decades and chi-square and t-tests were applied wherever applicable. A total of 3425 acute burn patients were included in the study between 1977 and 2020, corresponding to a mean of 89 patients/year. Mean age was 3.60 ± 4.12 years, three quarters of all patients were preschool children (0-5 years) and mean total body surface area (TBSA) burned was 8.01% ± 9.57%, however only around one fifth had severe burns (>10% TBSA). Scald burns (65.31%) and flame burns (32.99%) were most commonly seen. Linear regression analysis showed the total number of thermal injuries treated at our center to have increased significantly as of 2004 (p < 0.001). Separate analysis showed the same for small and medium (<10% TBSA) burns (p < 0.001), whereas the number of severe burns did not increase significantly. Length of stay (LOS) was highly associated with %TBSA burned. The percentage of female patients amongst all patients increased over time (p = 0.012). LOS per TBSA burned decreased significantly (p < 0.001). The present data show pediatric burns to remain a major health burden in Switzerland, especially small and medium burns in preschool children. Prevention programs should focus on this age population as well as on scald and flame burns as most common etiologies. The observed decrease in length of stay suggests a major improvement in overall quality of care in pediatric burns and supports centralization of care.

Limited donor sites and poor long-term outcomes with standard treatment for large skin defects remain a huge problem. An autologous, bilayered, laboratory-grown skin substitute (denovoSkin™) was developed to overcome this problem and has shown to be safe in ten pediatric patients in a phase I clinical trial after transplantation. The goal of this article is to report on 48 months long-term results. The pediatric participants of the phase I clinical trial were followed at yearly visits up to five years after transplantation. Safety parameters including occurrence of adverse events, possible deviations of vital signs and changes in concomitant therapy as well as additional parameters regarding skin stability, scar quality and tumor formation were assessed. Furthermore, scar maturation was photographically documented. From the ten patients treated with denovoSkin^TM in this phase I clinical trial, seven completed the five-year follow-up period. Skin substitutes continued to be deemed safe, remained stable and practically unchanged, with no sign of fragility, and no tumor formation at clinical examination. Scar quality, captured by applying the Patient and Observer Scar Assessment Scale, was evaluated as close to normal skin. Transplantation of this laboratory-grown skin substitute in children is to date considered safe and shows encouraging functional and aesthetical long-term results close to normal skin. These results are promising and highlight the potential of a life-saving therapy for large skin defects. A multicentre, prospective, randomized phase II clinical trial to further evaluate the safety and efficacy of this novel skin substitute is currently ongoing.

Autologous skin substitutes represent a promising advancement in the treatment of burn injuries, offering personalized solutions for patients with extensive skin loss. This white paper synthesizes the current knowledge on laboratory-generated autologous skin substitutes in Europe, incorporating expert opinions and legal considerations. The white paper examines the scientific principles underlying autologous skin substitute development, including cell sourcing, bioengineering techniques, and clinical applications. The regulatory framework governing the production and use of these advanced therapies in Europe is also examined, highlighting challenges in standardization, safety, and approval pathways. The text features expert insights that offer a real-world perspective on the clinical viability and translational hurdles of autologous skin substitutes. The findings highlight the potential of autologous skin substitutes to improve burn treatment outcomes while emphasizing the need for harmonized regulations to facilitate clinical implementation. Despite technological advancements, significant challenges persist, including production costs, scalability, and long-term efficacy. Another focus of this white paper are the legal changes, which have significantly impacted the production and availability of these technologies. The review concludes that while autologous skin substitutes hold great promise, further research, regulatory refinement, and interdisciplinary collaboration are essential to optimize their integration into clinical practice.

For burn surgery, major therapeutic challenges are shortage of autologous donor sites for split-thickness skin, and massive devastating scarring. We investigated the therapeutic role of denovoSkin™, a bio-engineered autologous skin, in a prospective, randomized, controlled phase IIb clinical trial compared to the gold standard the split thickness skin graft (STSG). Patients, ≥12 years, with deep partial and/or full-thickness burns requiring surgical wound coverage were enrolled at four sites in Switzerland, the Netherlands, and Italy. Two comparable skin defects (max. 98 cm² each) per patient were intra-patient randomized to denovoSkin™ (experimental) or autologous STSG (control) treatment. Safety assessments were performed in all patients. Primary efficacy endpoint was the ratio of biopsy size to grafted area with take 4 weeks post-grafting. The analyses of the primary efficacy variable were performed on the modified Full Analysis Set (mFAS) and the per protocol set (PPS) with the analysis on the mFAS as the primary analysis. Other efficacy endpoints included wound closure and scar quality. Efficacy and safety follow-ups were conducted up to 12 months post-grafting. The trial started in March 2018 and completed recruitment in July 2022 and is registered at clinicaltrials.gov (NCT03227146). 21 patients were enrolled between March 26, 2018, and July 26 2022. 13 patients were included in the PPS. There were no significant safety differences between denovoSkin™ and STSG. 164 serious adverse events were observed (81%). Only two (hematoma and partial skin necrosis) could be related to denovoSkin™. They rapidly healed spontaneously. The expansion ratio for denovoSkin™ versus STSG was 7·0 times larger for denovoSkin™ (p < 0·001). In the mFAS the mean expansion ratio for denovoSkin™ was 10·76 (SD 6·03), and for STSG it was 1·70 (SD 0·68). The mean ratio of the two expansion ratios (denovoSkin™/STSG) was 7·41 (SD 4·87). By month 3, experimental and control areas were fully epithelialized. Scar evaluation up to 12 months post-grafting revealed no clinically relevant scarring for denovoSkin™, but mostly hypertrophic scarring for STSG. DenovoSkin™ is a novel and safe treatment option for deep burns. It lessens the need for conventional grafting and so spares donor sites. In sharp contrast to STSG, denovoSkin™ grafting showed minimal scarring, a finding never evidenced before in a randomized trial. This study was financed by Wyss Zurich Translational Center (project “denovoSkin”) and CUTISS AG.

For pediatric patients with full-thickness burns, achieving adequate dermal regeneration is essential to prevent inelastic scars that may hinder growth. Traditional autologous split-thickness skin grafts alone often fail to restore the dermal layer adequately. This study evaluates the long-term effect of using a NovoSorb^® Biodegradable Temporizing Matrix (BTM) as a dermal scaffold in four pediatric patients, promoting dermal formation before autografting. Pediatric burn patients treated at the University Children’s Hospital Zurich between 2020 and 2022 underwent a two-step treatment involving NovoSorb^® BTM application, followed by autografting. Histological analysis, conducted through 22 punch biopsies taken up to 2.6 years post-application, demonstrated robust dermal reorganization, with mature epidermal regeneration and stable dermo-epidermal connections. Immunofluorescence staining showed rapid capillary ingrowth, while extracellular matrix components, including collagen and elastic fibers, gradually aligned over time, mimicking normal skin structure. By 2.6 years, the dermal layer displayed characteristics close to uninjured skin, with remnants of NovoSorb^® BTM degrading within five months post-application. This study suggests that NovoSorb^® BTM facilitates elastic scar formation, offering significant benefits for pediatric patients by reducing functional limitations associated with inelastic scarring.