2. Academic Validation
  3. Engineering a stem cell-embedded bilayer hydrogel with biomimetic collagen mineralization for tendon-bone interface healing

Engineering a stem cell-embedded bilayer hydrogel with biomimetic collagen mineralization for tendon-bone interface healing

  • Bioact Mater. 2025 Mar 10:49:207-217. doi: 10.1016/j.bioactmat.2025.03.001.
Tingyun Lei 1 2,  Tao Zhang 1,  Tianshun Fang 3,  Jie Han 3,  Chunyi Gu 4,  Youguo Liao 5,  Yang Fei 1 2,  Junchao Luo 1 3,  Huanhuan Liu 6 7,  Yan Wu 1,  Weiliang Shen 1 2,  Xiao Chen 1,  Zi Yin 8 9,  Junjuan Wang 4
Affiliations

Affiliations

  • 1 Department of Sports Medicine & Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
  • 2 Binjiang Institute of Zhejiang University, Hangzhou, Zhejiang Province, China.
  • 3 Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, China.
  • 4 School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou, Zhejiang Province, China.
  • 5 Department of Burns and Wound Care Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 6 Ohio Musculoskeletal and Neurological Institute (OMNI), Ohio University, Athens, OH, USA.
  • 7 Department of Biomedical Sciences, Ohio University Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA.
  • 8 Department of Orthopedic Surgery of Sir Run Run Shaw Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, China.
  • 9 Institute of Cell Biology, Zhejiang University, Hangzhou, China.
PMID: 40130078 DOI: 10.1016/j.bioactmat.2025.03.001
Abstract

The tendon-bone interface effectively transfers mechanical stress for movement, yet its regeneration presents significant clinical challenges due to its hierarchical structure and composition. Biomimetic strategies that replicate the distinctive characteristics have demonstrated potential for enhancing the healing process. However, there remains a challenge in developing a composite that replicates the nanostructure of the tendon-bone interface and embeds living cells. Here, we engineered a nanoscale biomimetic bilayer hydrogel embedded with tendon stem cells for tendon-bone interface healing. Specifically, the biomimetic hydrogel incorporates intra- and extrafibrillar mineralized collagen fibrils as well as non-mineralized collagen fibrils resembling the tendon-bone interface at the nanoscale. Furthermore, biomimetic mineralization with the presence of cells realizes living tendon-bone-like tissue constructs. In the in vivo patella-patellar tendon-interface injury model, the tendon stem cell-laden biomimetic hydrogel promoted tendon-bone interface regeneration, demonstrated by increased fibrocartilage formation, improved motor function, and enhanced biomechanical outcomes. This study highlights the potential of the stem cell-laden biomimetic hydrogel as an effective strategy for tendon-bone interface regeneration, offering a novel approach to engineering complex tissue interfaces.

Keywords

Biomimetic mineralization; Hydrogel; Tendon stem cell; Tendon-bone interface.

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