Biomimetic multilayer scaffolds with prolonged retention of stem cells-recruiting and angiogenic peptides for promoting bladder regeneration

The complications of enterocystoplasy have challenged traditional bladder reconstruction methods. Tissue engineering scaffolds, involving stem cells implantation and vascularization strategies, emerge as promising alternatives. However, their applications are hindered by issues regarding the source of stem cells and the rapid loss of bioactive factors in a urinary environment. Here, a multilayer biomimetic scaffold consisting of polycaprolactone (PCL) nanofibrous mats and oxidized dextran/carboxymethyl chitosan hydrogel has been synthesized. Bone marrow homing peptide (BMHP) and vascular endothelial growth factor-mimicking peptide (VP) were incorporated into the hydrogel to recruit endogenous stem cells and promote vascularization, respectively. The results indicated that PCL mats not only reinforced the mechanical properties of composite scaffolds but also prolonged the retention of peptides via the hydrophobic surface. In vivo experiments demonstrated that BMHP and VP had crosstalk effects, amplifying their functions to accelerate bladder regeneration, enhance contractility of smooth muscle cells, inhibit fibrosis, and improve innervation. Overall, the novel functionalized scaffolds are potentially viable for urologic tissue reconstruction.