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Bladder pain syndrome (BPS) and overactive bladder (OAB) affect approximately 1 in 100 women and 1 in 10 people, respectively. While these conditions affect a significant portion of the population, long-term symptom relief is challenging and commonly requires multiple invasive treatments. For example, BPS treatment with glycosaminoglycan (GAG) replenishment therapy requires multiple inter-bladder injections over six months for treatment efficacy to be realized. To reduce the treatment burden on patients and improve treatment efficacy in a single procedure, we developed a tissue interfacing crosslinked hydrogel to act as a GAG replenishment scaffold. Highly extensible hydrogels with minimal hysteresis were formulated to mimic the properties of the bladder and be stable in simulated urine. When applied to porcine bladder tissue, both ex vivo and in vivo, the hydrogel coatings were observed to evenly integrated into the urothelium even when repeatedly extended and minimally effect the mechanical properties of the bladder. Further, the incorporation and retention of GAGs into the network was investigated. Collectively, these results demonstrate the potential for tissue integrating tissues to act as not only a new modality for the treatment of bladder diseases, but through adaptation, the augmentation and treatment of various tissues.