Highlight
Two-to-four key highlights of this study include:
1. DenovoSkin™ achieved a 7.4-fold higher expansion ratio compared to the gold standard split-thickness skin graft (STSG), significantly reducing the need for donor site harvesting.
2. One-year follow-up data revealed minimal to no clinically relevant scarring in areas treated with denovoSkin™, whereas STSG control areas predominantly developed hypertrophic scars.
3. The safety profile of the bio-engineered graft was comparable to conventional methods, with only two minor, self-resolving adverse events directly related to the experimental treatment.
Background: The Persistent Challenge of Burn Reconstruction
In the management of severe burns, particularly deep partial-thickness and full-thickness injuries, the surgical standard of care has long been the autologous split-thickness skin graft (STSG). While effective, STSG is limited by two major clinical bottlenecks: the finite availability of healthy donor sites in cases of massive burns and the high incidence of debilitating hypertrophic scarring. These scars often lead to functional contractures, chronic pain, and significant psychological distress for patients.
Tissue engineering has sought to address these limitations by creating dermo-epidermal substitutes that can be expanded in vitro from a small patient biopsy. DenovoSkin™ represents a breakthrough in this field, consisting of an autologous, bio-engineered skin graft that includes both epidermal and dermal components. This prospective, randomized, controlled multicenter phase IIB clinical trial was designed to evaluate whether this technology could provide a viable, and perhaps superior, alternative to the current gold standard.
Study Design and Methodology
The trial (NCT03227146) was conducted across four specialized burn centers in Switzerland, the Netherlands, and Italy. The study population included 21 patients (adolescents aged ≥12 years and adults) presenting with deep burns requiring surgical intervention.
Utilizing a rigorous intra-patient randomized design, two comparable skin defects (up to 98 cm² each) were identified on each patient. One site was randomized to receive the experimental denovoSkin™ graft, while the other received a conventional STSG (the control). This design effectively controlled for individual patient healing characteristics and systemic factors.
The primary efficacy endpoint was defined as the expansion ratio—the ratio of the original biopsy size to the successfully grafted area with ‘take’ at 4 weeks post-grafting. Secondary endpoints included the timeline to complete wound closure, safety assessments, and long-term scar quality evaluated up to 12 months using standardized clinical scales. The analysis was performed on both a modified Full Analysis Set (mFAS) and a Per Protocol Set (PPS).
Results: Redefining Expansion and Scar Quality
Between 2018 and 2022, 21 patients were enrolled, with 13 patients completing the full protocol for the PPS analysis. The findings represent a significant milestone in regenerative medicine.
Primary Efficacy: The Expansion Ratio Advantage
The most striking finding was the massive difference in expansion potential. In the mFAS, denovoSkin™ demonstrated a mean expansion ratio of 10.76 (SD 6.03), compared to just 1.70 (SD 0.68) for the STSG. Statistically, the expansion ratio for denovoSkin™ was 7.41 times larger than that of the control (p < 0.001). This confirms that a significantly smaller donor biopsy can cover a much larger wound area when processed through the denovoSkin™ bio-engineering pipeline, a factor of critical importance in patients with extensive body surface area burns.
Safety and Tolerability
Safety was monitored extensively over the 12-month period. While 164 serious adverse events (SAEs) were recorded across the study population (a high number reflecting the critical nature of burn injuries), the vast majority were unrelated to the experimental graft. Only two adverse events—a localized hematoma and a focal area of partial skin necrosis—were attributed to denovoSkin™. Both instances resolved spontaneously without the need for additional surgical intervention. No systemic safety concerns or immunological rejections were observed, confirming the biocompatibility of the autologous construct.
Long-term Outcomes: Scarring and Aesthetic Results
Perhaps the most clinically meaningful result for the patients was the quality of the healed skin. By month 3, both experimental and control sites achieved full epithelialization. However, as the maturation process continued toward the 12-month mark, the differences became pronounced. Areas treated with denovoSkin™ showed virtually no clinically relevant scarring. In sharp contrast, the control sites treated with STSG mostly developed hypertrophic scarring, characterized by elevation, redness, and loss of elasticity. This finding is unprecedented in a randomized controlled trial for burn surgery and suggests that the inclusion of a bio-engineered dermal layer facilitates more natural tissue remodeling.
Expert Commentary: A Paradigm Shift in Tissue Engineering
From a clinical perspective, these results address the “holy grail” of burn surgery: achieving permanent wound coverage with minimal donor site morbidity and superior cosmetic/functional outcomes. The 7.4-fold expansion advantage is a game-changer for surgeons managing major burns where donor skin is a scarce commodity.
Mechanistically, the success of denovoSkin™ likely stems from its dermo-epidermal structure. Unlike simple epidermal sheets used in previous decades, which were fragile and prone to scarring, the presence of a structured dermal scaffold in denovoSkin™ provides the necessary mechanical stability and signaling environment to prevent the overactive collagen deposition that leads to hypertrophic scars.
However, it is important to note the study’s limitations. The sample size, while appropriate for a Phase IIB trial, remains relatively small. Additionally, the complex manufacturing process required for autologous bio-engineered skin—involving biopsy shipping, laboratory expansion, and specialized handling—presents logistical and cost challenges that must be addressed before widespread adoption in trauma centers.
Conclusion
The 1-year results of this Phase IIB trial establish denovoSkin™ as a safe and highly effective alternative to split-thickness skin grafting for deep burns. By providing a vastly superior expansion ratio and nearly eliminating the risk of hypertrophic scarring, this technology offers a new horizon for burn rehabilitation. As we move toward larger Phase III trials, the focus will likely shift toward optimizing the scalability of the production process and integrating this advanced therapy into standard clinical workflows.
Funding and Trial Registration
This study was supported by the Wyss Zurich Translational Center and CUTISS AG. The trial is registered at clinicaltrials.gov under the identifier NCT03227146.
References
Meuli M, Schiestl C, Hartmann-Fritsch F, et al. Safety and efficacy of bio-engineered, autologous dermo-epidermal skin grafts in adolescent and adult burn patients: 1-year results of a prospective, randomized, controlled, multicenter phase IIB clinical trial. EClinicalMedicine. 2025 Nov 28;90:103665. doi: 10.1016/j.eclinm.2025.103665. PMID: 41399471.