This application describes the synthesis, characterization, and evaluation of a hydrogel dressing that dissolves and can be easily removed from the wound surface of a patient with second degree burns with no further trauma. Burns are one of the most common and devastating forms of trauma. Each year, more than 300,000 people die from fire-related burn injuries and millions suffer from burn-related disabilities and disfigurements with psychological, social, and economic effects on both the survivors and their families. Dressing removal is reported to be the time of most pain (after the burn itself) and opioids continue to be the mainstay of treatment for the burn patient. The duration of a burn dressing change in a typical injury requiring ICU/OR level care is often at least 60 minutes with induction of general anesthesia, which can extend to more than three hours depending on the case. At present, all clinically approved available dressings adhere to the wound surface so that each change of dressing leads to traumatization of newly formed tissues on the outer layer of the body's surface, delayed healing, and great personal suffering for the injured patient. The application describes a thiol- terminated dendron and a bifunctional NHS-activated PEG that react with each other to form a thioester-linked hydrogel dressing that can be subsequently dissolved by exposure of an aqueous thiol solution via a thiol- thiolester exchange mechanism. The proposed experiments will test the hypothesis that a hydrogel- based, dissolvable burn dressing will provide a barrier to infection, promote wound healing, and be easily removable on demand. Importantly, it presents preliminary data demonstrating the synthesis, characterization, and performance of a dissolvable hydrogel dressing prototype.
The specific aims of this four- year application are:
Aim 1 : Synthesize and characterize a series of hydrogel burn dressings;
Aim 2 : Determine the in vitro toxicity and biocompatibility, as well as in vivo compatibility after subcutaneous implantation of the dissolvable dressing;
and Aim 3 : Evaluate the efficacy of the dissolvable dressing in vivo.
Burns are one of the most common and devastating forms of trauma with more than 300,000 people dying each year from fire-related burn injuries and millions suffering from burn-related disabilities and disfigurements. Successful design, synthesis and characterization of a novel dissolvable hydrogel dressing for the treatment of second degree burns will result in: 1) a dissolvable hydrogel dressing; 2) the development of structure-activity relationships and design requirements for such a dressing; 3) performance evaluation in two relevant in vivo models; and 4) collection of robust data for analysis, discussion, and further hypothesis generation.
|Konieczynska, Marlena D; Grinstaff, Mark W (2017) On-Demand Dissolution of Chemically Cross-Linked Hydrogels. Acc Chem Res 50:151-160|
|Konieczynska, Marlena D; Villa-Camacho, Juan C; Ghobril, Cynthia et al. (2016) On-Demand Dissolution of a Dendritic Hydrogel-based Dressing for Second-Degree Burn Wounds through Thiol-Thioester Exchange Reaction. Angew Chem Int Ed Engl 55:9984-7|
|Ghobril, Cynthia; Rodriguez, Edward K; Nazarian, Ara et al. (2016) Recent Advances in Dendritic Macromonomers for Hydrogel Formation and Their Medical Applications. Biomacromolecules 17:1235-52|