Biomimetic Constructs for Achilles Tendon Regeneration and their Translation to Human Medicine

Abstract Background: Achilles tendon injuries are among the most common lower-body tendon injuries, often resulting fromoveruse and repetitive motion. Current treatments, ranging from conservative therapies to biological grafts, have drawbacks, including limited regenerative capacity and the risk of graft rejection. To overcome these challenges, tissue engineering shows growing promise for Achilles tendon regeneration, with ongoing research focused on developing biomimetic constructs that utilize various materials and biologics. Since every tendon has unique biomechanical and physiological characteristics, it is crucial to conduct individualized evaluations through detailed research and to address key considerations for clinical translation. Methods: This review focuses explicitly on advances in Achilles tendon tissue engineering for human medicine, assessing constructs made from natural, synthetic, and composite materials with/without biologics and discussing their clinical translation. Studies were searched in the PubMed database and Google Scholar, using the most relevant keywords, such as “Achilles tissue engineering”, “Achilles biomimetic constructs”, “Biomaterials for Achilles tendon”, and “Clinical translation”. Results: Biomimetic constructs developed from various polymers and their combinations, when integrated with stem cells, demonstrate promising potential to reconstruct tissue microenvironments in vitro and to facilitate tissue repair and biomechanical functions in vivo. Carefully developing each element, including appropriate material structures, is essential for optimizing cell responses, biomechanical properties, and tissue repair in the Achilles tendon. Although the in vitro and in vivo advances reviewed in the paper contribute to clinical research, further studies with reproducible, long-term outcomes are needed to make the constructs clinically applicable in human medicine. Conclusion: Achilles tissue engineering continues to progress, driven by a deeper understanding of the injuries and the integration of regenerative tools. Furthermore, clinical considerations, such as long-term in vivo follow-up to assess biocompatibility and functional recovery, will be critical to achieving clinical outcomes. Graphical Abstract