Repairing injured tendon or ligament attachments to bones (enthesis) remains costly and challenging. Despite superb surgical management, the disorganized enthesis newly formed after surgery accounts for high recurrence rates after operations. Tissue engineering offers efficient alternatives to promote healing and regeneration of the specialized enthesis tissue. Load-transmitting functions thus can be restored with appropriate biomaterials and engineering strategies. Interestingly, recent studies have focused more on microstructure especially the arrangement of fibers since Rossetti successfully demonstrated the variability of fiber underspecific external force. In this review, we provide an important update on the current strategies for scaffold-based tissue engineering of enthesis when natural structure and properties are equally emphasized. We firstly described compositions, structures and features of natural enthesis with their special mechanical properties highlighted. Stimuli for growth, development and healing of enthesis widely used in popular strategies are systematically summarized. We discuss the fabrication of engineering scaffolds from the aspects of biomaterials, techniques and design strategies and comprehensively evaluate the advantages and disadvantages of each strategy. At last, this review pinpoints the remaining challenges and research directions to make breakthroughs in further studies.

Introduction: Polyetheretherketone (PEEK) has good biosafety and chemical stability for bone repair. However, PEEK is biologically inert and cannot promote bone apposition. This study investigated whether graphene-modified PEEK (G-PEEK) could improve cell adhesion and osteogenic differentiation. Methods: G-PEEK was prepared by melted blending and was characterized. In vitro, the biocompatibility of G-PPEK and the ability to promote cell adhesion and osteogenic differentiation in rabbit bone marrow mesenchymal stem cells (rBMSCs) were examined using live and dead cell double staining, the cell counting kit-8 (CCK-8) assay, immunofluorescence and quantitative real-time PCR (qRT‒PCR). An in vivo rabbit extra-articular graft-to-bone healing model was established. At 4 and 12 weeks after surgery, CT analysis and histological evaluation were performed. Results: In vitro, G-PEEK significantly improved the adhesion and proliferation of rBMSCs, with good biocompatibility. In vivo, G-PEEK promoted new bone formation at the site of the bone defect. Conclusion: G-PEEK showed excellent osteogenesis performance, which promises new applications in implant materials.