Dissolvable hydrogel-based wound dressings for in vivo applications
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Controlled hydrogel dissolution allows for: 1) atraumatic material removal after it served its function, 2) site-specific delivery of encapsulated therapeutics (e.g., proteins, small molecules), and 3) a tailored administration of an agent with high efficiency. Dissolution of covalently crosslinked hydrogels has been accomplished by incorporating cleavable moieties that undergo ester hydrolysis or enzymatic degradation. Recently, thiol-disulfide exchange, retro Michal-type reactions, retro Diels-Alder reactions, and thiol-thioester exchange chemistries have gained attention, as they provide a responsive synthetic handle for engineering hydrogel dissolution rates. We synthesized, characterized and tested in vivo two on-demand dissolvable dendritic thioester hydrogel dressings for second-degree burn care and hemorrhage control. The hydrogels are composed of lysine-based dendrons and PEG-based crosslinkers, which were prepared in high yields. In context of hemorrhage, there is an unmet clinical need for an on-demand dissolvable sealant for non-compressible hemorrhage or areas of body not amenable to treatment with a torniquet. In a model of in vivo hemorrhage control of intra-abdominal wounds, our hydrogel reduced blood loss by 33% in severe hepatic hemorrhage and by 22% in aortic injury, as compared to untreated controls. There is an unmet clinical need for a second-degree burn dressing that can be removed atraumatically and serve as a barrier to bacterial infection. When our hydrogel was used as a dressing, local and systemic bacterial proliferation after wound contamination was significantly lower than in the untreated group. The total bacterial burden of the burn wound in the positive controls was significantly higher than in the hydrogel group and the negative controls (1.39x10E8 ± 8.30x10E7 CFU/g v. 4.04x10E3 ± 3.99x10E3 CFU/g v. 6.88x10E2 ± 6.38x10E2 respectively; P = 0.009). Also, the total systemic bacterial burden in the positive controls was significantly higher than the hydrogel group and the negative controls (9x10E2 ± 7.76x10E7 CFU/g v. 5x10E1 ± 0 CFU/g v. 5x10E1 ± 0 CFU/g, respectively; P = 0.031). A unique feature of both hydrogel systems is their capability to be dissolved on-demand via thiol-thioester exchange reaction with a biocompatible solution following its initial application – thus the wound area can be re-exposed to allow for definitive surgical care.