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However, there is very limited breakthrough in achieving favorable bone regeneration due to the harsh osteogenic microenvironment after bone injury, especially the avascular and hypoxic conditions. Inspired by the bone developmental mode of endochondral ossification, a novel strategy is proposed for tolerant and rapid endochondral bone regeneration using framework\u2010enhanced 3D biomineralized matrix hydrogels. First, it is meticulously designed 3D biomimetic hydrogels with both hypoxic and osteoinductive microenvironment, and then integrated 3D\u2010printed polycaprolactone framework to improve their mechanical strength and structural fidelity. The inherent hypoxic 3D matrix microenvironment effectively activates bone marrow mesenchymal stem cells self\u2010regulation for early\u2010stage chondrogenesis via TGF\u03b2\/Smad signaling pathway due to the obstacle of aerobic respiration. Meanwhile, the strong biomineralized microenvironment, created by a hybrid formulation of native\u2010constitute osteogenic inorganic salts, can synergistically regulate both bone mineralization and osteoclastic differentiation, and thus accelerate the late\u2010stage bone maturation. Furthermore, both in vivo ectopic osteogenesis and in situ skull defect repair successfully verified the high efficiency and mechanical maintenance of endochondral bone regeneration mode, which offers a promising treatment for craniofacial bone defect repair.<\/jats:p>","DOI":"10.1002\/advs.202305580","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T15:02:38Z","timestamp":1703170958000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Tolerant and Rapid Endochondral Bone Regeneration Using Framework\u2010Enhanced 3D Biomineralized Matrix Hydrogels"],"prefix":"10.1002","volume":"11","author":[{"given":"Baoshuai","family":"Bai","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory of Tissue Engineering Department of Plastic and Reconstructive Surgery of Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 200011 P. R. 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