A retrospective matched‐cohort study of 3994 lower extremity wounds of multiple etiologies across 644 institutions comparing a bioactive human skin allograft, TheraSkin, plus standard of care, to standard of care alone

Abstract

Most chronic wounds are related to comorbidities, for which no clinical trials are performed. This retrospective propensity matched-cohort study examined data from 2 074 000 lower extremity wounds across 644 institutions to determine the effectiveness of TheraSkin plus standard of care (SOC; n = 1997) versus SOC alone (n = 1997). Multivariate modelling comparing outcomes such as healing rates, percent area reductions (PARs), amputations, recidivism, treatment completion, and medical transfers were evaluated. A higher proportion of wounds in the treatment group compared with the controls were more likely to close (68.3% versus 60.3%), particularly wounds with exposed structures (64% versus 50.4%) and with lower recidivism at 6 months (24.9% versus 28.3%). The control group was 2.75x more likely to require amputation than the treatment group. The combination of propensity matching and logistic regression analysis on a particularly large database demonstrated that wounds treated with TheraSkin had higher healing rates, higher PARs (78.7% versus 68.9%), fewer amputations, lower recidivism, higher treatment completion (61.0% versus 50.6%), and lower medical transfers (16.1% versus 23.5%) than SOC alone. This study considered data from complex wounds typically excluded from controlled trials and supports the idea that real-world evidence studies can be valid and reliable.

Cryopreserved human skin allografts promote angiogenesis and dermal regeneration in a murine model

“…These findings indicate that the cellular response to CHSA might elicit a remodelling process of the dermis leading to a less fibrotic collagen fibre alignment, which preserves the physiologic basket weave appearance of the dermis. Our data might provide a biologic explanation for the improved healing rates of chronic wounds treated with CHSA compared with standard of care alone, which were demonstrated in large retrospective matched‐cohort studies …”

“…The beneficial effects of human skin allograft transplantation have been known for decades, particularly in the treatment of major burn injuries. Skin allografts have been shown to accelerate the healing of burn wounds and more also recently of chronic wounds . As an immunogenic organ, allo‐ or xenografted skin by nature induces an immune response, ultimately leading to fibrotic encapsulation and rejection by the host .…”

“…Beyond the initial goal of temporary wound coverage to decrease fluid loss and prevent infections, skin allografts have also shown beneficial effects in the treatment of major burns by preparing the wound bed for future autograft applications. Skin allografts have been shown to improve wound regeneration not only in burns but also in chronic venous as well as diabetic lower leg ulcers, leading to higher healing rates compared with bioengineered skin substitutes . The most commonly used methods for preservation of human skin allografts in tissue banks are dehydration using highly concentrated glycerol or cryopreservation (−20 to −196°C).…”

Current and Emerging Topical Scar Mitigation Therapies for Craniofacial Burn Wound Healing

“…Although the host immune response to allograft precludes its use as a permanent skin replacement, achieving temporary wound coverage with allograft stimulates the release of a variety of bioactive substances that accelerate wound closure (Katz and Taichman, 1994). Clinical trials have shown that skin allografts can accelerate the healing of burn wounds as well as chronic wounds in the lower extremity (Nuñez-Gutiérrez et al, 1996;Gurtner et al, 2020). It has been shown that the viability of skin allografts correlates with take rate (Bravo et al, 2000;Castagnoli et al, 2003), thus effective techniques for preservation of skin grafts are critical to maintain high quality grafts.…”

“…Cryopreservation is the preferred method of cadaveric skin preservation, since it better maintains the physicochemical properties and viability of fresh human skin compared to glycerol ( Aggarwal et al, 1985 ; Cinamon et al, 1993 ; Pirnay et al, 2012 ). Recently developed human cryopreserved meshed split-thickness skin allografts such as TheraSkin ® (Misonix, Farmingdale, NY, United States) have shown promising results in the treatment of chronic wounds in clinical trials ( DiDomenico et al, 2011 ; Gurtner et al, 2020 ) and demonstrated regenerative properties in pre-clinical studies ( Henn et al, 2020 ), suggesting a potential future therapeutic role in burn care as well.…”