A functional universal sandwich biomimetic scaffold with both repair effect and drug delivery system effectively facilitates bladder regeneration

Bladder reconstruction is one of the most challenging issues for urological surgery. Currently available scaffolds have limitations such as inefficient smooth muscle regeneration, graft contracture, and stone formation. Here, inspired by the native bladder, we have designed a functional universal sandwich biomimetic scaffold (PSP) with both repair effect and drug delivery system utilizing a membrane-hydrogel-membrane structure. The hydrogel and responsive microspheres acted as a dual-controlled release system for succinate (SA), an effective small molecule which can block the occurrence and growth of crystal. The double-sided membrane was made from a novel decellularized matrix-based procyanidin-crosslinked small intestine submucosa (PC–SIS) material, which has shown a great promise for bladder smooth muscle regeneration. While the luminal side of the membrane was modified with a femtosecond laser micro-machining system for the release of SA. In vitro assays showed that the scaffolds have superior biocompatibility and anti-calcification properties. Animal studies shown that the PSP scaffolds could facilitate early epithelial reconstruction and reduce the risk for stones by regulating immunological, osteogenic, and ion transport processes. Toward the end of treatment, the volume of regenerated bladder and compliance of the PSP group were much greater compared with those sandwich hydrogel. The multifunctional universal sandwich biomimetic scaffolds therefore can provide a promising strategy for the reconstruction of urinary bladders.