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While the focus has often been on restoring organogenesis stem cells, there is limited investigations of reverting the environmental niche to support this approach. The guiding principle of \u201cNature selects the fittest to survive\u201d drives the intricate dynamic changes in cellular events within the niche environment, especially through immune surveillance. The extracellular matrix (ECM) serves as the \u201cself\u2010associated molecular patterns\u201d of the niche, containing extensive data on cell\u2010niche reaction data and acting as the active tuner of immune surveillance. In this study, hyaluronic acid (HA) is identified as a unique component of the ECM in cranial osteo\u2010organogenesis. Mechanistically, HA activates the Cluster of Differentiation 44 (CD44)\u2010Mitogen\u2010Activated Protein Kinase (MAPK)\/Extracellular Signal\u2010Regulated Kinase (ERK)\u2010Ets Variant 1\/5 (ETV1\/5)\u2010 Mannose Receptor C\u2010Type 1 (MRC1) axis in macrophages, establishing a distinct immune surveillance during osteo\u2010organogenesis. Furthermore, HA is utilized as a novel engineered material for an \u201cOsteo\u2010organogenesis niche\u201d, restoring immune surveillance and synergistically regulating stem cells to achieve re\u2010osteo\u2010organogenesis in cranial defects of rats. Taken together, the study unveils a previously unknown strategy for leveraging re\u2010organogenesis by utilizing \u201corganogenesis niche\u201d ECM engineered materials to manipulate immune surveillance, thereby comprehensively regulating stem cells and other tissue cells effectively for re\u2010organogenesis.<\/jats:p>","DOI":"10.1002\/adhm.202403122","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T06:08:44Z","timestamp":1729663724000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["\u201cOsteo\u2010Organogenesis Niche\u201d Hyaluronic Acid Engineered Materials Directing Re\u2010Osteo\u2010Organogenesis via Manipulating Macrophage CD44\u2010MAPK\/ERK\u2010ETV1\/5\u2010MRC1 Axis"],"prefix":"10.1002","volume":"13","author":[{"given":"Zongpu","family":"Han","sequence":"first","affiliation":[{"name":"Hospital of Stomatology Guanghua School of Stomatology Sun Yat\u2010sen 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