The Ruptured Achilles Tendon Elongates for 6 Months After Surgical Repair Regardless of Early or Late Weightbearing in Combination With Ankle Mobilization: A Randomized Clinical Trial.

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Abstract

[Indexed for MEDLINE] 14. Sci Transl Med. 2025 Dec 10;17(828):eado6948. doi: 10.1126/scitranslmed.ado6948. Epub 2025 Dec 10. A bioinspired mineralized collagen scaffold promotes enthesis healing and activates Gli1 expression in preclinical models. Zhang T(1)(2), Lei T(1)(2), Han J(1)(2), Chen Y(3), Nie Y(2)(4)(5), Zhang R(1)(2)(5), Cai H(1)(2), Guo Z(2)(4)(5), Yan R(1)(2)(5), Li Z(6), Xu Y(1)(2), Zhang X(2)(5), Xu H(7), Chen J(7), Liao Y(1)(2), He Q(1)(2), Zhang H(3), Chen J(8), Zhu S(9), Guo J(7), Liu Y(7), Pan H(10), Chen J(7), Yin W(7), Ouyang H(1)(2)(5), Shen W(1)(2), Yin Z(4)(5), Tang R(10)(11), Chen X(1)(2)(5)(12). Author information: (1)Department of Sports Medicine & Orthopedic Surgery, Second Affiliated Hospital and Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China. (2)Zhejiang Key Laboratory of Motor System Disease Precision Research and Therapy, Hangzhou City, Zhejiang, China. (3)Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China. (4)Sir Run Run Shaw Hospital and Liangzhu Laboratory, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China. (5)Dr. Li Dak Sum-Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China. (6)PET Center, Department of Nuclear Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. (7)School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China. (8)Department of Clinical Medicine, School of Medicine, Hangzhou City University, Hangzhou, Zhejiang 310058, China. (9)Department of Biomedical Sciences, Ohio Musculoskeletal and Neurological Institute (OMNI), Diabetes Institute (DI), Ohio University, Athens, OH 45701, USA. (10)Department of Chemistry & Institute of Fundamental and Transdisciplinary Research, Zhejiang University, Hangzhou, Zhejiang 310058, China. (11)Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China. (12)State Key Laboratory of Transvascular Implantation Devices, Hangzhou, Zhejiang 310058, China. The enthesis, a fibrocartilaginous tissue connecting tendon or ligament to bone, is critical for joint movement but lacks regenerative capacity after injury. Current clinical treatments for enthesis healing remain limited. Here, with a resolution of 2 to 3 nanometers, we found that mineral particles form a continuous cross-fibrillar phase with a discontinuous distribution in the fibrocartilage layer. Building on this finding, we developed a series of bioinspired mineralized collagen matrices, characterized by both intra- and extrafibrillar localization of crystallites, with a tunable mass percentage of inorganic content as scaffolds for enthesis repair. Our results revealed that mineralized collagen with controlled inorganic content (33% mineral content) facilitated fibrocartilage healing across multiple animal enthesis injury models, including mice, rats, rabbits, and goats. In direct comparisons with other biomaterials in a rabbit model, the bioinspired mineralized collagen resulted in 82% fibrocartilage width recovery, more than two times the healing observed with other materials. Treatment with the bioinspired mineralized collagen scaffold produced joint healing with an ability to sustain a higher maximum load in both rat and rabbit models, with the animals able to walk normally. The goat model exhibited an improvement in jumping ability. Mechanistically, we found that the bioinspired mineralized collagen modulated Hedgehog signaling intensity in a mineralization-dependent manner, which in turn up-regulated Gli1 expression. This modulation regulated the differentiation of mesenchymal progenitor cells and promoted fibrocartilage healing. Overall, we demonstrate that a bioinspired mineralized collagen scaffold effectively promotes enthesis injury repair, demonstrating potential for clinical translation. DOI: 10.1126/scitranslmed.ado6948