Integrated 'Shield-Spear' Biological Patch for Fibrosis-Free Bladder Reconstruction.

Abstract

Bladder reconstruction without fibrosis remains a global challenge. Current bladder defect treatments primarily focus on repair at the level of vascularization, failing to balance healing and excessive collagen deposition, and neglecting the exacerbation of fibrosis due to neural dysregulation. In this study, an integrated 'shield-spear' patch composed of an anionic 'shield' hydrogel (HAD) and neuro-targeted 'spear' engineered extracellular vesicles (S100Aptamer-EVs) using Schiff base chemistry and Michael addition reactions is engineered. This novel approach represents the first attempt to synergistically balance the contradiction between fibrosis and wound healing through the 'shield-spear' strategy, achieving extensive bladder reconstruction without fibrosis. In a large animal model of beagles, the outer layer of the 'shield-spear' patch acts as an anionic shield, neutralizing scavenger receptors and selectively capturing GATA6peritoneal macrophages to suppress collagen overexpression. The inner layer enables the unidirectional release of S100AptEVs, targeting the activation of Schwann cells to express the brain-derived neurotrophic factor neuroprotective factor, downregulating the TGFβ/Smad fibrosis pathway, thereby collaboratively inhibiting neurogenic fibrosis and activating Cadherin signaling to promote wound healing. The integrated 'shield-spear' patch facilitated surgical manipulation in large animals and provides a promising approach for tissue-engineered bladder reconstruction without fibrosis.