Tendons enable locomotion through the transfer of muscular force across skeletal segments and actively stabilise joints. Their unique structure and organisation provide an efficient and effective system to minimise energy expenditure associated with movement. Strikingly, given their key role, they display a poor capacity for repair beyond late adolescence, and little or no capacity for regeneration to full function following injury. This stark position is furthered by the observation that ~30% of musculoskeletal referrals result from damaged tendons. This translates into an annual socioeconomic burden in excess of €150 Bn for the USA and EU alone.

This poor repair capability, coupled with both high frequency of injuries and cost, positions tendon repair at the forefront of stem cell-driven regenerative medicine approaches. Severe challenges remain widespread in the translation of fundamental bioscience into clinical applications within the field. These challenges include the lack of widely accepted tendon differentiation models, producing difficulties in the development of in vitro models, an essential necessity for progress in this area. Furthermore, the field continues to lack robust animal models with both comparative anatomy and fidelity of repair mechanisms. Crucially, tendon repair requires a complex collaboration of multiple cell types providing structural, immunological, neurological, and vasculature contributions. Advanced 3D models providing key signalling and mechanical cues are therefore required to further our understanding of this crucial musculoskeletal tissue.

This Special Issue is led by complementary international expertise. We will seek to establish a perspective on the state-of-the-art in stem cell-based solutions to understanding tendon biology, developing tendon repair solutions through controlled differentiation, presenting existing clinical approaches, and characterising hybrid system approaches incorporating stem cells, biomechanical forces, and biomaterial chemistry-driven solutions in the creation of future therapeutic approaches.

Potential topics include but are not limited to the following:

• Stem cell-driven models of tendon differentiation
• Tendon stem cells
• Tendon tissue engineering strategies
• The application of 3D system dynamic culture for ex vivo tendon models
• Additive manufacturing approaches
• Synthetic extracellular matrix generation
• Incorporation of biomimetic materials into tendon repair strategies
• Micro and nanotechnology approaches to repair and drug delivery
• Controlled immunomodulation in tendon repair
• In vivo models of tendon repair