Grant for Skin-on-Chip research on burn-induced tissue loss
Paul Krijnen (project leader) and hDMT PI Sue Gibbs (foto) of the Amsterdam UMC and Magda Ulrich (Association of Dutch Burn Centres) received a four-year grant from TKI-LSH Health Holland for their project NETosis in burn-induced microvascular thrombosis in the skin and wound deepening: a causative factor, biomarker and therapeutic target.
In burned patients, the conversion of partial-thickness burn wounds to deeper or full-thickness burn wounds is a common occurrence. This wound deepening leads to increased tissue loss, delayed healing, more hypertrophic scarring and contractures, an increased need for surgical excisions and grafting and an increased chance of burn wound infections and death. So far no effective treatment exists to prevent wound deepening.
The reseachers recently found extensive microvascular thrombosis in and around burn wounds in animal models and patients. The formation of these thrombi persisted for up to weeks after burn injury. As this can drastically reduce blood flow to the affected skin, microvascular thrombosis presumably is an important contributor to wound deepening and suboptimal healing. Moreover, they found evidence that points to neutrophil extracellular trap (NETs) formation as a crucial driver of post-burn microvascular thrombosis. NETosis describes the process whereby neutrophils eject net-like structures comprised of their DNA and pro-coagulant and pro-inflammatory proteins. NETosis has been shown to be a major initiator of blood coagulation and microvascular damage. NETosis may therefore be a promising therapeutic target to prevent microvascular thrombosis and wound deepening in burn patients.
The project aims to unravel the mechanisms underlying burn-induced NETosis and resultant microvascular thrombosis and damage and to determine how these relate to wound deepening and suboptimal healing. As a means to unravel the mechanisms, it is studied whether therapeutic inhibition of NETosis can counteract post-burn thrombosis and microvascular damage.
The results of this project can be a stepping-stone for the development of therapy that will significantly improve the quality of life for burn patients in the future.
Institutes and company involved in this project: Pathology and Molecular Cell Biology and Immunology (MCBI) Amsterdam UMC, Association of Dutch Burns Centers (ADBC) and Pharming.