Three-dimensional bioprinting and tendon repair: application advances and future directions

Abstract

BACKGROUND: Currently, three-dimensional (3D) bioprinting technology, with its controllable multi-scale structure and functional integration design capabilities, has become a cutting-edge solution for tendon tissue engineering. OBJECTIVE: To systematically summarize the latest research progress of 3D bioprinting technology in tendon repair. METHODS: Using the keywords “3D printing, bioink, myotendinous junction, tendon repair, tendon-bone junction, bionic scaffold,” literature searches were conducted in the PubMed and Web of Science databases, as well as in the China National Knowledge Infrastructure (CNKI) with the same keywords. Articles with weak relevance to the topic were excluded, and 109 articles were ultimately included for review. RESULTS AND CONCLUSION: 3D bioprinting technology, through multi-material integration and controllable biomimetic structural design, effectively reproduces the multi-level structure of tendons. Mainstream technologies (such as melt electrowriting, extrusion-based printing, etc.) play differentiated advantages in fiber alignment, interface simulation, and dynamic regulation, constructing mechanical transition layers at the muscle-tendon interface and four-zone gradient structures at the tendon-bone interface. Functionalized bioink innovations (immunomodulatory materials, cross-species oxygen-supplying scaffolds, etc.) and multi-technology synergy (aligned fiber deposition + photocuring reinforcement) enhance scaffold bioactivity and mechanical-biological coupling. In the full healing cycle (support in the inflammatory phase, guidance in the proliferative phase, regulation in the remodeling phase), precise intervention from molecular to macroscopic levels is achieved, optimizing collagen alignment and repair mechanical properties. Differentiated repair strategies (multi-material gradients, aligned fibers, gradient scaffolds) for the muscle-tendon interface, tendon body, and tendon-bone interface have made progress. Despite challenges such as resolution-efficiency contradictions and insufficient material matching, 3D printing technology still provides new strategies for tendon repair from structural biomimicry to functional regeneration. In the future, the integration of intelligent materials (photothermal/piezoelectric) and multimodal technologies (4D printing, organoids) is expected to promote dynamic functional regeneration and provide technical references for interface repair.

1. Introduction

Tendons, as core mechanical transmission structures connecting muscle to bone, directly influence the precision and stability of limb movement. Natural tendons exhibit excellent tensile properties through highly aligned multi-level collagen fibers (from nano-fibrils to macroscopic fiber bundles), and rely on the elastic transition at the myotendinous junction and the four-zone gradient structure at the tendon-bone interface (collagen type transitions from type I to type II and type X, with progressive mineralization) to achieve soft-to-hard tissue mechanical adaptation, ensuring efficient transmission of movement loads. However, the low cell density, avascular nature, and defective regenerative microenvironment (e.g., stem cell deficiency, inflammatory imbalance) severely limit tendon regeneration capacity—clinical functional recovery rates are only 60%-70%, and the risk of re-injury is significantly increased. Moreover, the myotendinous and tendon-bone interfaces often form fibrous scars due to mechanical mismatch, further exacerbating functional impairment.

Traditional repair techniques such as suturing and autograft/allograft transplantation can restore anatomical continuity but fail to reconstruct the biomimetic mechanical transmission pathway of tendons: suturing is prone to re-rupture due to stress concentration, while transplantation faces issues of limited donor availability, immune rejection, and poor interface integration, all of which cannot effectively address the heterogeneous repair challenges at the myotendinous and tendon-bone interfaces. In recent years, 3D printing technology, with its unique advantages of multi-material integration, controllable structural biomimicry, and dynamic biological regulation, has provided breakthrough strategies for tendon repair. By integrating patient imaging data with computer-aided design, 3D printing can precisely construct mechanical transition layers at the myotendinous junction and four-zone gradient structures at the tendon-bone interface. Combined with functionalized bioink innovations (e.g., immunomodulatory materials, cross-species oxygen-supplying scaffolds) and multi-technology synergy (e.g., extrusion-based aligned fiber deposition with photocuring reinforcement), it enables full-cycle intervention from inflammatory phase support, proliferative phase guidance, to remodeling phase regulation, significantly optimizing collagen alignment and repair mechanical properties. Although 3D printing technology has shown significant potential, it still faces technical bottlenecks and clinical translation challenges: mainstream technologies exhibit resolution-efficiency contradictions, shear forces easily cause cell damage, and material degradation does not match mechanical requirements. Additionally, research is mostly laboratory-based, lacking long-term safety data, and the synergistic study of complex biological processes such as neurovascular regeneration is insufficient.