Improving the Redissolution Kinetics of Thermoresponsive Hydrogels for Biomedical Applications in Higher Temperatures

Stimuli-responsive materials that respond to specific triggers, such as thermoresponsive hydrogels, are in high demand for biomedical applications. Due to their biocompatibility and water content similar to tissue, they have been used as contact lenses, wound healing bioadhesives, and drug delivery platforms. Biocompatible thermoresponsive sealant (TRS) is of great interest in the wound management of those injuries that risk substantial impairment with delayed treatment, such as open globe ocular injuries. TRS exhibits non-adhesive behavior at cold temperatures and is easily deployed; however, it becomes viscous and adhesive at body temperature and is capable of sealing penetrating injuries. Fast and reversible phase transitions of TRS upon cooling are required for their application after storage in variable temperatures. The kinetics of redissolution of a thermally treated TRS is slower for high molecular weight materials.<br/><br/>Herein we present a unique strategy for significantly increasing the redissolution kinetics of thermoresponsive hydrogels via the utilization of a high surface area host material. As an example of any other injectable in-situ forming hydrogels, which have suitable mechanical strength but slow transition times, the increase in the redissolution kinetics of hydrophobically-modified poly(N–isopropyl acrylamide) (pNIPAM) in the presence of a high surface area, open cell foam host is demonstrated. The recovery measurements show enhanced recovery (74-99%) across a range of foam types and pore sizes when compared to samples stored without a host (9% recovery). Maximizing a host surface area with an open cell foam demonstrated the greatest increase (~ten-fold) in TRS recovery after storing the TRS solution at 50 ^○C and cooling for ten minutes. The rheological analysis revealed that the viscosity, storage, loss modulus, and mechanical strength are not significantly affected by storage over a foam host.<br/><br/><br/>This work is supported by the US Army Medical Research and Materiel Command under Contract No.W81XWH-16-C-0086, and partially was supported under Research Project Award MTEC-20-14-Ocular-006 as executed by Delivery Order No. W81XWH-21-9-0003.