Tendon and tendon-bone interface (TBI) injuries—commonly affecting the rotator cuff, Achilles tendon, and anterior cruciate ligament—remain a persistent challenge in orthopedic practice. These injuries often heal with disorganized scar tissue rather than regenerating the native hierarchical structure, leading to compromised mechanical function and high re-tear rates. Autografts and allografts remain standard care but carry inherent drawbacks: donor site complications, limited graft availability, and failure to recapitulate the graded mineralization and collagen organization of a healthy enthesis.
Silk fibroin (SF), a natural fibrous protein derived primarily from Bombyx mori silkworm cocoons, has emerged as a compelling biomaterial platform for addressing these gaps. In their review, corresponding authors Dr. Xiao Chen and Dr. Zi Yin, along with first authors Dr. Ziang Guan and Dr. Sicheng Zhou from the Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cells and Regenerative Medicine at Zhejiang University School of Medicine, China, detail how SF's unique combination of high tensile strength (300–740 MPa), tunable biodegradability, and low immunogenicity makes it suited for musculoskeletal tissue engineering. Their review was published online in the Chinese Medical Journal on August 24, 2026.
The review systematically examines the structural hierarchy of silk from amino acid sequences through β-sheet nanocrystallites to nanofibril networks, and explains how each level contributes to the material's mechanical performance. The authors catalog the fabrication of regenerated SF into five principal scaffold formats: particles and films, hydrogels, sponges, polymeric fibers, and emerging hybrid constructs. Each format is evaluated against the specific mechanical and biological demands of tendon and TBI repair. For example, electrospun SF nanofibers can be aligned to mimic the anisotropic collagen architecture of native tendon, while gradient-mineralized scaffolds recapitulate the spatial transition from soft tendon to mineralized bone at the enthesis.
Beyond structural mimicry, the review highlights bioactive functionalization strategies—incorporating stem cells, growth factors (TGF-β, BMP-2, CTGF), and osteoinductive nanoparticles into SF scaffolds—to actively guide tissue regeneration. The authors also survey silk-based applications in adjacent fields, including skin wound healing, peripheral nerve repair, myocardial infarction treatment, and osteosarcoma therapy, underscoring the versatility of the material platform.
Despite rapid progress, the authors caution that significant hurdles remain. Few silk-based products have entered clinical trials; the exceptional mechanical properties of native silk fibers are not yet fully recovered in regenerated SF scaffolds; and the integration of multiple gradient types (physical, chemical, and biological) into single constructs remains technically demanding. Looking forward, the review envisions smart silk-based scaffolds incorporating sensors for non-invasive monitoring of graft strain and machine learning-driven material screening to accelerate the discovery of optimized formulations. "Silk-based materials have shown great application potential in tendon and TBI regeneration due to their excellent biocompatibility, tunable mechanical properties, and controllable biodegradability," the authors conclude.
Reference
Title of original paper: Silk-based materials: Emerging for tendon/tendon-bone regeneration
Journal: Chinese Medical Journal
DOI: https://doi.org/10.1097/CM9.0000000000004175
About Dr. Xiao Chen from Zhejiang University School of Medicine, China
Dr. Xiao Chen is a faculty member at the Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Zhejiang University School of Medicine. His research focuses on musculoskeletal tissue engineering, with an emphasis on biomaterial-based strategies for tendon and osteochondral regeneration. Dr. Chen and his collaborators have published extensively on silk fibroin scaffolds, stem cell-mediated repair, and the design of gradient biomaterials that recapitulate the native tendon-bone interface. His work integrates materials science, cell biology, and translational orthopedics to develop next-generation regenerative therapies.
Funding information
This work was supported by grants from the NSFC grants (No. 32271406，No. 32471211), and the Key R&D Program of Zhejiang (No. 2024C03077).
