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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 \u2018shield\u2010spear\u2019 patch composed of an anionic \u2018shield\u2019 hydrogel (HAD) and neuro\u2010targeted \u2018spear\u2019 engineered extracellular vesicles (S100Aptamer\u2010EVs) 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 \u2018shield\u2010spear\u2019 strategy, achieving extensive bladder reconstruction without fibrosis. In a large animal model of beagles, the outer layer of the \u2018shield\u2010spear\u2019 patch acts as an anionic shield, neutralizing scavenger receptors and selectively capturing GATA6\n                    <jats:sup>+<\/jats:sup>\n                    peritoneal macrophages to suppress collagen overexpression. The inner layer enables the unidirectional release of S100AptEVs, targeting the activation of Schwann cells to express the brain\u2010derived neurotrophic factor neuroprotective factor, downregulating the TGF\u03b2\/Smad fibrosis pathway, thereby collaboratively inhibiting neurogenic fibrosis and activating Cadherin signaling to promote wound healing. The integrated \u2018shield\u2010spear\u2019 patch facilitated surgical manipulation in large animals and provides a promising approach for tissue\u2010engineered bladder reconstruction without fibrosis.\n                  <\/jats:p>","DOI":"10.1002\/advs.202503975","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T12:42:06Z","timestamp":1755088926000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Integrated \u2018Shield\u2010Spear\u2019 Biological Patch for Fibrosis\u2010Free Bladder Reconstruction"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6838-3042","authenticated-orcid":false,"given":"Xiaoqi","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Urology and Andrology Ren Ji Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 200001 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