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.
Highlights
The theory of burn wound conversion refers to the phenomenon of progressive tissue necrosis from the zone of coagulation to the zone of stasis after cessation of the initial injury [1]
To investigate the impact clostridial collagenase has on the zone of stasis in burn wounds, we used a brass comb burn porcine model to create a total of 16 burn injuries in two animals (2 animals × 8 burns × 2 treatments) (Figure 1A)
We sought to better understand the impact clostridial collagenase debridement has on burn wounds and hypothesized that collagenase treatment prepares the burn environment to stabilize the zone of stasis, a critical area for burn progression of tissue surrounding the coagulated surface of a burn, and transition to healthy tissue rather than expansion of necrosis and apoptosis
Summary
The theory of burn wound conversion refers to the phenomenon of progressive tissue necrosis from the zone of coagulation to the zone of stasis after cessation of the initial injury [1]. Emanating from the devitalized zone of coagulation, secondary necrosis of partial-thickness to deep or full-thickness wounds is largely attributed to decreased vascular perfusion and an associated inflammatory response within the zone of stasis. Appropriate treatment of these burns represents a unique challenge to both experienced and inexperienced medical professionals due to the complexity of wound assessment and ongoing pathophysiology, risking delays in therapy to prevent additional tissue loss. Current clinical burn care is directed at treatment modalities to prevent this conversion of the burn wound These modalities include appropriate resuscitation, management (either surgical or non-surgical) of the burn wound, attention to nutrition, repletion and management of hyper-metabolic response. Minor achievements have been made [3,4], the translation to clinical practice has not yet been realized
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