Mechanically Matched PGT Hydrogel Enables Functional Bladder Augmentation and Reconstruction without Fibrosis
Tao Yang, Jiale He, Minghai Ma, Kaibo Mi, Yutong Chen, Min Wang, Hang Liu, Yanjia Liu, Nan Zhang, Dawei Luo, Mengzhao Zhang, Lei Wang, Jinhai FanAbstract
Background: The clinical translation of engineered bladder scaffolds often faces challenges due to a mechanical mismatch with native tissue, which can lead to complications such as urine leakage, graft fibrosis, reduced compliance, and rupture. This study aims to overcome these limitations by developing a biomimetic hydrogel with viscoelastic properties that precisely match those of the natural bladder. Methods: A novel hydrogel (PGT) was synthesized by combining acrylated polycaprolactone/polyethylene glycol triblock polymer (PCECD) with gelatin methacryloyl (GelMA), followed by hydrogen-bond crosslinking using tannic acid (TA). Nine PGT formulations with varying concentrations and PCECD/GelMA ratios were fabricated. Their mechanical properties were systematically characterized. Biocompatibility was assessed in vitro using urothelial cells, and functional efficacy was evaluated in vivo using a rabbit model of augmentation cystoplasty. Methods: A novel hydrogel (PGT) was synthesized by combining acrylated polycaprolactone/polyethylene glycol triblock polymer (PCECD) with gelatin methacryloyl (GelMA), followed by hydrogen-bond crosslinking using tannic acid (TA). Nine PGT formulations with varying concentrations and PCECD/GelMA ratios were fabricated. Their mechanical properties were systematically characterized. Biocompatibility was assessed in vitro using urothelial cells, and functional efficacy was evaluated in vivo using a rabbit model of augmentation cystoplasty. Results: A specific formulation (10% concentration, PCECD:GelMA ratio of 1:1) demonstrated mechanical properties closely matched to the native bladder and exhibited excellent cytocompatibility in vitro. In the rabbit model, implantation of the optimized PGT hydrogel significantly improved bladder capacity and compliance compared to controls. Histological analysis revealed rapid epithelialization, with complete urothelial regeneration achieved within one month. Critically, the repaired tissue showed no evident fibrosis, indicating successful avoidance of this common pathological outcome. Conclusions: We successfully developed a mechanically biomimetic PGT hydrogel that supports functional bladder reconstruction. These findings underscore the pivotal role of precise mechanical compatibility in bladder tissue engineering, promoting regenerative healing while preventing fibrosis. This study provides a promising material strategy and a clear direction for future research toward effective clinical bladder augmentation.