Bioprinting-based approaches for tendon reconstruction: A decade of advancement

Table 1 Tendon-specific preclinical studies of printed constructs

Ref.	Species and model	Construct composition and fabrication	Cell source and integration method	Comparator	Main outcome and follow-up
Jiang et al[19]	Rabbit; rotator cuff tendon-to-bone reconstruction	Multilayered zonal construct; 3D bioprinting combined with melt electrowriting	Autologous ADMSCs pre-differentiated along tenogenic, chondrogenic and osteogenic lineages, printed within the bioink	Acellular printed scaffold; repair without construct	At 12 weeks, enthesis mechanical properties improved vs repair without construct; ADMSC incorporation conferred no detectable further gain. Superior histological score and collagen organisation vs acellular scaffold
Chae et al[14]	Rat; chronic rotator cuff tear	Graded tendon-bone interface patch; tendon- and bone-specific decellularized ECM bioinks	Stem cells encapsulated and printed within the bioink	Repair without patch	Accelerated and enhanced tendon-bone interface healing; high cell viability and zonal-specific differentiation of encapsulated cells
Chae et al[20]	Rat; rotator cuff repair	Gradient multi-tissue construct; compositional gradient dECM bioinks	MSCs printed within the bioink in a gradient arrangement	Tear; repair-only; native tendon control	At 12 weeks, ultimate load to failure, elastic modulus and ultimate stress higher than repair-only; graded interface regeneration and improved shoulder locomotion
Kim et al[21]	Rabbit; rotator cuff tear	Multi-layered gradient core-shell construct (aligned tendon, graded interface, reinforced bone); tendon- and bone-specific dECM bioinks with hydroxyapatite and TGF-β/PVA	Human adipose stem cells printed within the bioink via core-shell nozzle	Tear; repair; non-graded printed construct; native control	At 8 weeks, highest maximum load and stiffness of all groups; significantly greater than tear and repair, but below native tissue (n = 4)
Zhang et al[22]	Rabbit; unrepairable massive rotator cuff tear (bridging)	3D-printed polycaprolactone scaffold loaded with tendon stem cell-derived exosomes and type I collagen	No living printed cells; cell-free exosome payload	Autologous fascia lata graft	Tendinous tissue regeneration at bridging site; histological and biomechanical properties not significantly different from autologous fascia lata repair
Kaneda et al[23]	Rat; Achilles tendon defect	Microgrooved polycaprolactone scaffold extruded through a patterned nozzle	iPSC-derived MSCs overexpressing scleraxis, seeded after scaffold fabrication	Microgrooved scaffold only; suture-only repair	Improved gait, biomechanical properties and tissue architecture vs scaffold-only and suture-only repair
Jiang et al[12]	In vitro; subcutaneous implantation for biocompatibility only (no tendon defect model)	3D-printed PLGA framework (layer-by-layer or tri-layered) combined with collagen-fibrin hydrogels	Human ADMSCs within cell-laden hydrogel combined with an acellularly printed framework	Single-layered printed PLGA scaffold	Uniaxial tensile properties of both multilayered constructs improved vs single-layered PLGA; supported ADMSC growth, proliferation and tenogenic differentiation; biocompatible at 2 weeks subcutaneously

Outcomes are stated as the endpoint measured and its direction relative to the stated comparator, with the follow-up interval given where reported; absolute values are available in the cited primary sources. ADMSCs: Adipose-derived mesenchymal stem cells; dECM: Decellularized extracellular matrix; ECM: Extracellular matrix; iPSC: Induced pluripotent stem cell; MSCs: Mesenchymal stem cells; PLGA: Poly(lactic-co-glycolic acid); PVA: Poly(vinyl alcohol); TGF-β: Transforming growth factor-β; 3D: Three-dimensional.

Table 2 Principal advances and remaining challenges in tendon bioprinting

Aspect	Advancement	Impact
Bioprinting techniques	Extrusion, laser-assisted, and inkjet approaches with improving control of spatial deposition	Supports fabrication of organised tendon-like and interface constructs
Bioink development	Collagen-, gelatin-, fibrin-, and ECM-derived bioinks combined with synthetic reinforcement	Balances biological activity with structural stability
Biological integration	Cell-laden and tissue-specific bioinks; ADMSCs and MSCs printed within the bioink; distinguished from constructs seeded after fabrication	Supports zonal organisation and tendon-bone interface regeneration in preclinical models
Preclinical evidence	Rabbit and rat tendon-to-bone models using multilayered or gradient constructs (Table 1)	Improved histological organisation and mechanical performance vs repair-only controls; relative contribution of architecture, bioink and cells not yet separated; human efficacy unestablished
Technical challenges	Vascularisation, in vitro mechanical properties, in vivo durability under cyclic loading, reproducibility, scale-up	Research focuses on vascular strategies, robust composite constructs, and reproducible workflows
Clinical and regulatory	Classification as device vs cell-based advanced therapy; potency, sterility and cell-source governance; RMAT and ATMP pathways; cost-effectiveness	Translational barriers distinct from technical ones; no bioprinted tendon construct has yet reached clinical evaluation

ADMSCs: Adipose-derived mesenchymal stem cells; ATMP: Advanced Therapy Medicinal Product; ECM: Extracellular matrix; MSCs: Mesenchymal stem cells; RMAT: Regenerative medicine advanced therapy.