Clostridium Collagenase Impact on Zone of Stasis Stabilization and Transition to Healthy Tissue in Burns
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, a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/16/8643 |
| _version_ | 1797523589898960896 |
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| author | Rosanne E. Frederick Robert Bearden Aleksa Jovanovic Nasreen Jacobson Rajiv Sood Sandeep Dhall |
| author_facet | Rosanne E. Frederick Robert Bearden Aleksa Jovanovic Nasreen Jacobson Rajiv Sood Sandeep Dhall |
| author_sort | Rosanne E. Frederick |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T08:45:07Z |
| format | Article |
| id | doaj.art-c164919d558246dabcd02d8db13b430a |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:45:07Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c164919d558246dabcd02d8db13b430a2023-11-22T07:58:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012216864310.3390/ijms22168643Clostridium Collagenase Impact on Zone of Stasis Stabilization and Transition to Healthy Tissue in BurnsRosanne E. Frederick0Robert Bearden1Aleksa Jovanovic2Nasreen Jacobson3Rajiv Sood4Sandeep Dhall5Smith & Nephew Plc., Fort Worth, TX 76107, USASmith & Nephew Plc., Fort Worth, TX 76107, USASmith & Nephew Plc., Fort Worth, TX 76107, USASmith & Nephew Plc., Fort Worth, TX 76107, USASmith & Nephew Plc., Fort Worth, TX 76107, USASmith & Nephew Plc., Fort Worth, TX 76107, USAClostridium 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.https://www.mdpi.com/1422-0067/22/16/8643collagenaseenzyme debridementburn conversionzone of stasis |
| spellingShingle | Rosanne E. Frederick Robert Bearden Aleksa Jovanovic Nasreen Jacobson Rajiv Sood Sandeep Dhall Clostridium Collagenase Impact on Zone of Stasis Stabilization and Transition to Healthy Tissue in Burns International Journal of Molecular Sciences collagenase enzyme debridement burn conversion zone of stasis |
| title | Clostridium Collagenase Impact on Zone of Stasis Stabilization and Transition to Healthy Tissue in Burns |
| title_full | Clostridium Collagenase Impact on Zone of Stasis Stabilization and Transition to Healthy Tissue in Burns |
| title_fullStr | Clostridium Collagenase Impact on Zone of Stasis Stabilization and Transition to Healthy Tissue in Burns |
| title_full_unstemmed | Clostridium Collagenase Impact on Zone of Stasis Stabilization and Transition to Healthy Tissue in Burns |
| title_short | Clostridium Collagenase Impact on Zone of Stasis Stabilization and Transition to Healthy Tissue in Burns |
| title_sort | clostridium collagenase impact on zone of stasis stabilization and transition to healthy tissue in burns |
| topic | collagenase enzyme debridement burn conversion zone of stasis |
| url | https://www.mdpi.com/1422-0067/22/16/8643 |
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