Biological tendon regeneration, are we almost there or is it still a stretch?

Tendon injuries are a major clinical challenge, affecting mil-lions worldwide and often resulting in impaired mobility,chronic pain, and high rates of re-injury. The adult tendon’spoor vascularity and low cellularity limit its regenerative capa-city, frequently leading to disorganized repair and fibrotic scarformation rather than functional tissue regeneration. Currenttherapeutic approaches, including orthobiologics andmesenchymal stromal/stem cells (MSCs), offer only modestbenefits due to issues such as donor variability, short-livedeffects, and poor reproducibility. Moreover, MSCs are oftendriven toward fibrotic or non-tenogenic lineages within theinjury microenvironment, further hindering effective repair.Recent advances in stem cell biology have enabled thegeneration of induced pluripotent stem cell (iPSC)-derivedtenocytes (iTenocytes), which show promise as a scalable, line-age-committed, and potentially hypoimmunogenic cellsource. These cells can be integrated with engineered bioma-terials, such as bioresorbable 3D-printed scaffolds, to enhancestructural support, guide tissue organization, and promotehost-mediated repair. Mimicking developmental signalingpathways has improved tenogenic differentiation, but chal-lenges remain in optimizing maturation stages and minimizingoff-target lineage formation. Moving forward, combiningiTenocytes with mechanically robust, cell-laden scaffolds andprecise biomechanical cues may enable scarless tendon regen-eration and full functional recovery, addressing a longstandingunmet clinical need in musculoskeletal medicine.