Clostridium Collagenase Impact on Zone of Stasis Stabilization and Transition to Healthy Tissue in Burns

Abstract

Clostridium collagenase has provided superior clinical results in achieving digestion of immediate and accumulating devitalized collagen tissue. Recent studies suggest that debridement via Clostridium collagenase modulates a cellular response to foster an anti-inflammatory microenvironment milieu, allowing for a more coordinated healing response. In an effort to better understand its role in burn wounds, we evaluated Clostridium collagenase’s ability to effectively minimize burn progression using the classic burn comb model in pigs. Following burn injury, wounds were treated with Clostridium collagenase or control vehicle daily and biopsied at various time points. Biopsies were evaluated for factors associated with progressing necrosis as well as inflammatory response associated with treatment. Data presented herein showed that Clostridium collagenase treatment prevented destruction of dermal collagen. Additionally, treatment with collagenase reduced necrosis (HMGB1) and apoptosis (CC3a) early in burn injuries, allowing for increased infiltration of cells and protecting tissue from conversion. Furthermore, early epidermal separation and epidermal loss with a clearly defined basement membrane was observed in the treated wounds. We also show that collagenase treatment provided an early and improved inflammatory response followed by faster resolution in neutrophils. In assessing the inflammatory response, collagenase-treated wounds exhibited significantly greater neutrophil influx at day 1, with macrophage recruitment throughout days 2 and 4. In further evaluation, macrophage polarization to MHC II and vascular network maintenance were significantly increased in collagenase-treated wounds, indicative of a pro-resolving macrophage environment. Taken together, these data validate the impact of clostridial collagenases in the pathophysiology of burn wounds and that they complement patient outcomes in the clinical scenario.

Eschar dissolution and the immunoregulator effect of keratinase on burn wounds

“…The skin of mice has epidermis and dermis, but it is thinner than that of humans, and the body size of mice is small, which leads to the establishment of III degree burn model and easy death. Pig is an ideal burn model animal, and previous studies have used porcine skin burn model as the subject of enzymatic debridement preparation 29 . However, the high cost and operation complexity of pigs as animal models limit the use of pigs in animal experiments.…”

In Vitro Study of a Novel Vibrio alginolyticus-Based Collagenase for Future Medical Application

“…Bacterial collagenases are a usual proteolytic family of enzymes responsible for the disintegration of tissue. Among these, the most recognized in medical practice is the lyophilized extract of Clostridium histolyticum [ 64 ]. However, collagenases extracted from C. histolyticum possess reduced protein selectivity, degrading not only collagen but other essential proteins as well [ 44 ], possibly influencing product regenerative capacity.…”

Sustained drug delivery to reduce the extent of burn progression

“…217 Furthermore, Federick et al, showed that Clostridium collagenase treatment to porcine skin burn wounds prevented the conversion of tissue in the zone of stasis via faster resolution in neutrophils and limiting necrosis and apoptosis (Frederick et al, 2021). In addition, Clostridium collagenase treatment prevented destruction of dermal collagen and burn conversion that often led to a significant delay in healing (Frederick et al, 2021). These findings support that the targeting the zone of stasis for burn therapies prevents burn progression and improves wound healing outcomes.…”

“…This in turn reduced the necrotic area, accelerated re-epithelization, and improved rat burn wound healing (Yucel et al, 2019). 217 Furthermore, Federick et al, showed that Clostridium collagenase treatment to porcine skin burn wounds prevented the conversion of tissue in the zone of stasis via faster resolution in neutrophils and limiting necrosis and apoptosis (Frederick et al, 2021). In addition, Clostridium collagenase treatment prevented destruction of dermal collagen and burn conversion that often led to a significant delay in healing (Frederick et al, 2021).…”