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Human dental pulp provides an accessible, structurally well\u2010defined injury model with robust clinical responses, facilitating in situ investigations of inflammatory signaling and endogenous regeneration. Here, we integrated high\u2010resolution spatial transcriptomics with single\u2010cell RNA sequencing (scRNA\u2010seq) to chart its cellular ecosystem in health and caries. We resolved five major cell classes and four odontoblast progenitor subtypes, reconstructing their differentiation trajectories. Spatial mapping of immune cells combined with cell\u2013cell communication analysis revealed that macrophages promote progenitor migration and odontoblastic differentiation via platelet\u2010derived growth factor B (PDGFB) signaling. Inspired by this axis, we developed a hydrogel that amplifies macrophage PDGFB delivery via adeno\u2010associated virus (AAV) vectors, which promoted mineralization in vitro and accelerated reparative dentin formation in a direct pulp\u2010capping mouse model. Downstream analyses and pathway perturbation further confirmed the role of the PDGFB\u2013Wnt\u2013RUNX2 signaling axis in these progenitors. This study provides a spatially resolved single\u2010cell framework showing how immune cues direct stem\/progenitor fate to orchestrate regeneration, offering a targeted design paradigm for pulp regeneration biomaterials.<\/jats:p>","DOI":"10.1002\/adhm.71573","type":"journal-article","created":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T12:39:27Z","timestamp":1786883967000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spatial Transcriptomics\u2010Inspired Targeted Hydrogel for Dental Pulp Therapy via Strengthen Macrophage Communication"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9674-2599","authenticated-orcid":false,"given":"Mingmei","family":"Yang","sequence":"first","affiliation":[{"name":"Hospital of Stomatology Guanghua School of Stomatology Sun Yat\u2010Sen University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Stomatology  Guangzhou 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