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Conventional tissue engineering approaches have primarily focused on promoting interface healing by stimulating regeneration in either the tendon or bone. However, these methods often fall short of achieving optimal therapeutic outcomes due to their neglect of balancing bone homeostasis and remodeling the microstructure at the osteoporotic tendon\u2010to\u2010bone interface. Herein, a series of site\u2010specific functional modifications are carried out on teriparatide to develop recombinant human parathyroid hormone (R\u2010PTH). A biomimetic microstructured reconstruction scaffold (BMRP) is constructed using a decalcified mussel shell scaffold, pre\u2010gel, and R\u2010PTH. The BMRP mimics the microstructures of the native tendon\u2010to\u2010bone interface and restores the original structure of the interface tissue by repairing injured cells, balancing bone homeostasis, and remodeling the microstructure of the osteoporotic tendon\u2010to\u2010bone interface. In an osteoporotic rotator cuff tear model, BMRP is in\u00a0situ implanted at the injured site, resulting in structural reconstruction and functional recovery. The BMRP demonstrates excellent repair effects, representing a novel therapeutical alternative for treating osteoporotic tendon\u2010to\u2010bone injury potential for clinical application.<\/jats:p>","DOI":"10.1002\/advs.202500144","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T04:30:52Z","timestamp":1742185852000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Biomimetic Microstructured Scaffold with Release of Re\u2010Modified Teriparatide for Osteoporotic Tendon\u2010to\u2010Bone Regeneration via Balancing Bone Homeostasis"],"prefix":"10.1002","volume":"12","author":[{"given":"Chengzhong","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Orthopaedics\u2010Spine Surgery Nanfang Hospital Southern Medical University  1838 North Guangzhou Ave Guangzhou 510515 P. R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gen","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics\u2010Spine Surgery Nanfang Hospital Southern Medical University  1838 North Guangzhou Ave Guangzhou 510515 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering School of Basic Medical Sciences Southern Medical University  Guangzhou 510515 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Stomatology Nanfang Hospital Southern Medical University  Guangzhou 510515 P. R. 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