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These scaffolds provide essential structural support and promote new bone formation by mimicking the native extracellular matrix (ECM). The rational design of an ideal scaffold requires careful balancing of biomaterial properties with biomechanical performance. Natural polymers have gained considerable attention in this context due to their inherent bioactivity, biocompatibility, and tunable mechanical properties. Their key advantage lies in their ability to replicate the complex architecture and function of bone ECM, thereby facilitating cellular interactions and tissue ingrowth. Recent progress in the processing and assembly of natural polymers has enabled innovative scaffold designs, including hydrogels as well as fibrous and porous architectures. These advances allow for the fabrication of scaffolds with precisely tailored features, such as optimal stiffness, controlled pore sizes, and surface topographies conducive to cell adhesion and differentiation. Furthermore, degradation kinetics can be adjusted to match the rate of new tissue formation. This review provides a comprehensive examination of the role of natural polymers in BTE. It critically discusses state-of-the-art fabrication techniques and highlights the critical physicochemical and biological properties that determine scaffold performance. By consolidating these key aspects, the review aims to identify current challenges and outline future directions for the development of natural polymer-based scaffolds. Ultimately, this work seeks to offer practical guidance for the rational design and translational advancement of these materials in bone regeneration.<\/jats:p>","DOI":"10.1021\/acsbiomaterials.6c00767","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T15:01:46Z","timestamp":1790953306000},"page":"5769-5801","source":"Crossref","is-referenced-by-count":1,"title":["Natural Polymer-Based Scaffolds for Bone Tissue Engineering: A Review of Materials, Function, and Translation"],"prefix":"10.1021","volume":"12","author":[{"given":"Ziyun","family":"Huang","sequence":"first","affiliation":[{"name":"Chongqing University , , ,","place":["Chongqing, China, 400044"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huilin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Chongqing University , , ,","place":["Chongqing, China, 400044"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4476-6019","authenticated-orcid":true,"given":"Zengzilu","family":"Xia","sequence":"additional","affiliation":[{"name":"Chongqing University , , ,","place":["Chongqing, China, 400044"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxi","family":"Wang","sequence":"additional","affiliation":[{"name":"Chongqing University , , ,","place":["Chongqing, China, 400044"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9029-680X","authenticated-orcid":true,"given":"Kaiyong","family":"Cai","sequence":"additional","affiliation":[{"name":"Chongqing University , , ,","place":["Chongqing, China, 400044"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,2]]},"reference":[{"key":"2026110907074457600_cit1","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.bioactmat.2025.08.007","article-title":"Nano MgO loaded thermosensitive HPCH@HA hydrogel accelerates in situ bone repair through osteoimmunomodulation while enhancing angiogenesis and osteogenesis","volume":"54","author":"Ni","year":"2025","journal-title":"Bioact. 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