BPG is committed to discovery and dissemination of knowledge
Minireviews Open Access
Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.
World J Orthop. Oct 18, 2026; 17(10): 126840
Published online Oct 18, 2026. doi: 10.5312/wjo.126840
Bioprinting-based approaches for tendon reconstruction: A decade of advancement
Mohammed Sarbaz Shakir, Division of Surgery and Interventional Sciences, University College of London, London WC1E 6BT, United Kingdom
ORCID number: Mohammed Sarbaz Shakir (0000-0002-0313-9134).
Author contributions: Shakir MS solely conceived, researched, drafted, revised, and approved the final version of this manuscript, and is accountable for all aspects of the work.
AI contribution statement: AI tools, specifically Grammarly (Grammarly Inc., current web version), were used solely for grammar checking, language polishing, and formatting assistance. No AI tool was used to design the review, select or interpret the cited literature, generate references, or formulate conclusions. All AI-assisted content was critically reviewed and revised by the author, who takes full responsibility for the accuracy, originality, and integrity of the manuscript.
Conflict-of-interest statement: The author declares that there are no conflicts of interest to disclose in relation to this manuscript.
Corresponding author: Mohammed Sarbaz Shakir, Division of Surgery and Interventional Sciences, University College of London, Gower Street, London WC1E 6BT, United Kingdom. mohammed.shakir.24@ucl.ac.uk
Received: August 14, 2026
Revised: August 26, 2026
Accepted: September 20, 2026
Published online: October 18, 2026
Processing time: 63 Days and 5.5 Hours

Abstract

Tendon injuries remain difficult to manage because tendon tissue is relatively hypocellular and hypovascular and has limited regenerative capacity. Autograft and allograft reconstruction is constrained by donor-site morbidity, graft availability, variable biological incorporation, and incomplete restoration of native structure and mechanical function. Three-dimensional bioprinting, defined here as additive fabrication in which living cells are deposited within or alongside biomaterials, enables patient-specific constructs that aim to more closely approximate the hierarchical architecture of native tendon. Over the past decade, extrusion-, inkjet-, and laser-assisted platforms, together with collagen-, gelatin-, fibrin-, and extracellular matrix derived bioinks and synthetic polymer reinforcement, have improved construct properties. Tendon-specific preclinical studies, particularly rotator cuff tendon-to-bone models, report improved histological organisation and higher failure load or stiffness relative to repair-only controls, although the incremental contribution of printed cells has been inconsistent. Vascularisation, mechanical durability under cyclic loading, reproducible scale-up, and regulatory classification remain unresolved. Stimulus-responsive and self-healing bioinks, multi-material printing, vascular co-printing, and computational optimisation are promising but largely lack tendon-specific in vivo validation. This narrative review appraises a decade of progress, distinguishes cell-laden bioprinting from acellular additive manufacturing, and outlines the translational barriers preceding clinical adoption.

Key Words: Three-dimensional bioprinting; Tendon reconstruction; Tissue engineering; Bioink; Regenerative medicine; Tendon scaffold; Mesenchymal stem cells; Musculoskeletal reconstruction

Core Tip: Three-dimensional bioprinting offers a patient-specific alternative to autografts and allografts for tendon reconstruction, using layered deposition of bioinks, cells, and growth factors to recreate the hierarchical architecture of native tendon. This review summarises a decade of progress in bioink formulation, printing hardware, and biological integration, and outlines the remaining barriers to clinical translation, principally vascularisation of thick constructs, regulatory approval, cost, and the training of surgical teams to work with this technology.



INTRODUCTION

Tendon injuries, whether traumatic or degenerative in origin, are common musculoskeletal disorders and remain difficult to treat because of the low cellularity and vascularity of tendon tissue[1]. Tendons transmit load between muscle and bone and are essential to musculoskeletal function, but their limited intrinsic capacity for regeneration means that healing often favours disorganised scar formation rather than restoration of native fibrillar architecture, particularly in chronic disease[1].

For substantial tendon defects or failed primary repair, graft-based reconstruction may be required, but autografts and allografts have recognised limitations, including donor-site morbidity, graft availability, biological incorporation, and incomplete restoration of native mechanical function[2]. These limitations continue to motivate the development of tissue-engineered alternatives.

In this review, three-dimensional (3D) bioprinting denotes additive fabrication in which living cells are deposited within or alongside biomaterials during the printing process itself. It is distinguished throughout from acellular additive manufacturing, in which a scaffold is printed first and cells, if used at all, are seeded onto it afterwards. The distinction is not semantic: Printing live cells constrains bioink viscosity, shear stress at the nozzle, crosslinking chemistry, and sterility, and it changes how a construct is classified by regulators[3,4]. Studies are therefore identified below according to whether cells were printed within the bioink, deposited spatially by another route, or seeded after fabrication.

Bioprinting enables the precise, sequential deposition of biomaterials, cells, and bioactive molecules into constructs tailored to an individual patient’s anatomy[3,4]. Where cells are incorporated during printing, the intention is to enhance biological integration and support tissue regeneration rather than to provide a purely structural graft[5].

Despite this promise, substantial obstacles remain. Two distinct mechanical problems are often conflated. The first is in vitro performance before implantation: Printed constructs must possess sufficient tensile strength and stiffness at the point of surgery to tolerate fixation and early loading. The second is in vivo durability during healing, where the construct must resist cyclic loading and progressive degradation while host tissue remodels. Reported in vitro properties do not reliably predict in vivo durability, and fatigue behaviour under physiological cyclic loading has rarely been characterised in tendon constructs[2,6] (Figure 1). Vascularisation of clinically sized constructs is a further limitation and is considered separately below.

Figure 1
Figure 1 Schematic representation of a hierarchically organised bioprinted tendon construct. A: Parallel collagen fibre bundles; B: Co-printed vascular channel network shown within the construct; C: Seeded cells.

This review traces the historical development of tendon bioprinting, summarises its current applications, appraises the tendon-specific preclinical evidence, and considers the clinical, economic, and regulatory factors that will shape its future adoption[2].

LITERATURE SEARCH STRATEGY

This is a narrative rather than a systematic review, and no formal risk-of-bias assessment or quantitative synthesis was undertaken. PubMed/MEDLINE, Scopus, and Web of Science were searched from database inception, with the search last updated in August 2026. The “decade” referred to in the title is defined as the ten-year period from January 2015 to December 2025, with the search extended to August 2026 in order to capture the most recent literature. Representative search terms combined bioprinting concepts (“3D bioprinting”, “bioprinting”, “bioink”, “additive manufacturing”, “3D printing”) with tissue-specific terms (“tendon”, “enthesis”, “tendon-to-bone”, “tendon-bone interface”, “rotator cuff”, “Achilles”), using Boolean operators and truncation. Reference lists of retrieved articles were hand-searched.

The inclusion focus for primary evidence was studies of printed constructs evaluated in tendon, enthesis, or tendon-to-bone models, whether in vitro or in vivo. Foundational and historical sources predating 2015 are cited where they establish the origins of the technology, and general biomaterials and biofabrication papers are cited only to support forward-looking discussion in the Future prospects section; these are identified as such in the text so that readers can distinguish tendon-specific evidence from evidence extrapolated from other tissues. English-language publications were included. Because selection was purposive rather than exhaustive, the possibility that relevant studies were not captured cannot be excluded.

HISTORICAL BACKGROUND

The conceptual foundation of bioprinting lies in Hull's 1986 development of stereolithography, an additive manufacturing process originally designed for industrial prototyping[7]. Its precision and scalability made it an attractive candidate for biomedical adaptation, and in the early 2000s researchers applied 3D printing principles to the fabrication of biological scaffolds capable of supporting tissue growth[8].

Early efforts concentrated on relatively simple, non-load-bearing tissues such as skin and cartilage. Alginate-based hydrogels featured prominently because of their capacity to approximate the extracellular matrix (ECM) and support cell proliferation[9]. Much of this early work involved acellular printed scaffolds that were seeded after fabrication; genuinely cell-laden printing became routine later. Subsequent advances in laser-assisted and extrusion-based printing improved the precision and scalability with which more complex architectures could be produced[10,11].

By the 2010s, the field had advanced sufficiently to address musculoskeletal tissues such as bone and tendon, which present a considerably greater fabrication challenge owing to their hierarchical, load-bearing structure. Collagen-, gelatin-, fibrin-, and ECM-derived bioinks became increasingly important because they provide biological cues that can be combined with mechanically stronger printed frameworks[12-14]. These materials span both categories: Some were printed acellularly and seeded subsequently[12], whereas others were formulated as cell-laden bioinks and extruded with encapsulated cells[13,14]. Concurrently, work on co-printed vascular networks demonstrated approaches to improving nutrient transfer in tissue-engineered constructs of clinically relevant size, although this work was conducted in soft-tissue rather than tendon models[15].

Bioprinting is now an established component of the regenerative medicine toolkit, and its evolution illustrates the importance of sustained collaboration between engineers, materials scientists, and clinicians in overcoming the technical barriers specific to musculoskeletal tissue[16].

CURRENT APPLICATIONS

Over the past decade, progress in tendon bioprinting has been driven by parallel advances in bioink formulation, printing method, and biological integration. Extrusion-based printing is well suited to higher-viscosity bioinks and composite constructs[17,18], while inkjet and laser-assisted platforms can offer higher spatial resolution for selected applications[10,18]. The choice of platform reflects a balance between cell viability, material viscosity, resolution, construct size, and mechanical requirements.

Collagen-, gelatin-, fibrin-, and ECM-derived hydrogels are commonly combined with mechanically stronger synthetic frameworks such as polycaprolactone or poly(lactic-co-glycolic acid) to balance biological activity with structural stability[12-14].

Tendon-specific preclinical evidence

Six studies provide the core tendon-specific preclinical evidence and are summarised in Table 1. Jiang et al[19] combined 3D bioprinting with melt electrowriting to produce zonal constructs in which autologous adipose-derived mesenchymal stem cells (ADMSCs), pre-differentiated along tenogenic, chondrogenic, and osteogenic lineages, were printed within the bioink. In a rabbit rotator cuff reconstruction model assessed at 12 weeks, the multilayered constructs improved the mechanical properties of the enthesis relative to repair without a construct, and the cell-laden group showed a superior histological score and improved collagen organisation compared with acellular scaffolds. The authors reported that incorporating autologous ADMSCs made a limited additional contribution to biomechanical performance at 12 weeks. It should be emphasised that this is a statement about an effect that was not detected in a small-sample animal study rather than a demonstration that printed cells confer no mechanical benefit; the study was not powered as an equivalence trial, and a later time point or larger sample might yield a different result.

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 reconstructionMultilayered zonal construct; 3D bioprinting combined with melt electrowritingAutologous ADMSCs pre-differentiated along tenogenic, chondrogenic and osteogenic lineages, printed within the bioinkAcellular printed scaffold; repair without constructAt 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 tearGraded tendon-bone interface patch; tendon- and bone-specific decellularized ECM bioinksStem cells encapsulated and printed within the bioinkRepair without patchAccelerated and enhanced tendon-bone interface healing; high cell viability and zonal-specific differentiation of encapsulated cells
Chae et al[20]Rat; rotator cuff repairGradient multi-tissue construct; compositional gradient dECM bioinksMSCs printed within the bioink in a gradient arrangementTear; repair-only; native tendon controlAt 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 tearMulti-layered gradient core-shell construct (aligned tendon, graded interface, reinforced bone); tendon- and bone-specific dECM bioinks with hydroxyapatite and TGF-β/PVAHuman adipose stem cells printed within the bioink via core-shell nozzleTear; repair; non-graded printed construct; native controlAt 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 collagenNo living printed cells; cell-free exosome payloadAutologous fascia lata graftTendinous tissue regeneration at bridging site; histological and biomechanical properties not significantly different from autologous fascia lata repair
Kaneda et al[23]Rat; Achilles tendon defectMicrogrooved polycaprolactone scaffold extruded through a patterned nozzleiPSC-derived MSCs overexpressing scleraxis, seeded after scaffold fabricationMicrogrooved scaffold only; suture-only repairImproved 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 hydrogelsHuman ADMSCs within cell-laden hydrogel combined with an acellularly printed frameworkSingle-layered printed PLGA scaffoldUniaxial tensile properties of both multilayered constructs improved vs single-layered PLGA; supported ADMSC growth, proliferation and tenogenic differentiation; biocompatible at 2 weeks subcutaneously

Chae et al[14] cell-printed tendon- and bone-specific decellularized ECM bioinks into a graded tendon-bone interface patch and evaluated it in a chronic rotator cuff model, reporting zonal differentiation of encapsulated stem cells and improved interface regeneration. In a subsequent study, Chae et al[20] implanted gradient multi-tissue constructs in a rat rotator cuff model and reported graded interface tissue regeneration and improved shoulder locomotion at 12 weeks, with ultimate failure load, elastic modulus, and ultimate stress all measured against repair-only and native controls. Jiang et al[12] took a hybrid approach, combining an acellularly printed polylactic-co-glycolic acid framework with cell-laden collagen-fibrin hydrogels containing human adipose-derived mesenchymal stem cells. Both multilayered configurations showed improved uniaxial tensile properties relative to a single-layered printed scaffold, and the hydrogel supported stem cell growth, proliferation and tenogenic differentiation. It is worth noting that this study did not include a tendon defect model: In vivo assessment was limited to two-week subcutaneous implantation to establish biocompatibility, so the construct’s performance under load in a tendon environment remains untested.

More recent work has extended these approaches and, importantly, has used different cell-integration strategies. Kim et al[21] used a core-shell nozzle system to bioprint a multi-layered construct comprising aligned tendon tissue, a gradient tendon-bone interface and a mechanically reinforced bone region, using tendon- and bone-specific decellularized ECM bioinks supplemented with hydroxyapatite and transforming growth factor-β/poly(vinyl alcohol), with human adipose stem cells printed within the bioink. In a rabbit rotator cuff tear model at eight weeks, the biologically graded constructs achieved the highest maximum load and stiffness of the groups tested, significantly exceeding both untreated tear and conventional repair, although values remained below those of native uninjured tissue. Zhang et al[22] took a different approach, loading tendon stem cell-derived exosomes and type I collagen into a 3D-printed polycaprolactone scaffold — a cell-free biological payload rather than living printed cells — to bridge unrepairable massive rotator cuff tears in a rabbit model; the construct produced tendinous tissue regeneration at the bridging site with histological and biomechanical properties that did not differ significantly from repair using autologous fascia lata. Kaneda et al[23] seeded induced pluripotent stem cell-derived mesenchymal stem cells overexpressing scleraxis onto microgrooved polycaprolactone scaffolds extruded through a patterned nozzle, and reported improved gait, biomechanical properties and tissue architecture in a rat Achilles defect model relative to scaffold-only and suture-only repair; here the cells were seeded after fabrication rather than printed. Liu et al[24] have reviewed the extent to which bioprinted scaffolds recapitulate hierarchical muscle-to-bone interfaces.

Read together, these studies consistently show that printed architecture improves histological organisation and mechanical performance relative to repair-only controls. What they do not yet establish is how much of that benefit is attributable to the printed geometry, the bioink composition, or the added cells, because the comparators differ between studies and few designs isolate the cellular contribution. Table 1 sets out the model, construct, cell-integration route, comparator, follow-up, and mechanical endpoint for each so that these variables can be compared directly.

VASCULARISATION OF BIOPRINTED TENDON CONSTRUCTS

Vascularisation is discussed here in a single place rather than distributed across sections, because the requirement is easily overstated for tendon specifically. Native tendon midsubstance is relatively hypovascular, and its cells tolerate a low-oxygen environment; the enthesis and the peritendinous tissues are comparatively better perfused. It does not follow that a bioprinted tendon construct needs a dense vascular network throughout, and the vascular requirements of the midsubstance and the tendon-to-bone interface may differ substantially.

The engineering problem is nonetheless real for constructs of clinically relevant thickness, where diffusion alone cannot sustain encapsulated cells during the interval between printing and host integration. Two strategies dominate. The first is perfusion bioreactor preconditioning, in which constructs are matured under flow before implantation. The second is co-printing of sacrificial or endothelialised channels seeded with endothelial cells and angiogenic cues, an approach demonstrated convincingly in soft-tissue constructs by Kolesky et al[15] but not, to date, validated in a tendon or enthesis model in vivo. Claims about vascular co-printing in tendon reconstruction should therefore be read as extrapolation from other tissues rather than as tendon-specific evidence.

FUTURE PROSPECTS

The trajectory of tendon bioprinting over the next decade will likely be shaped by three converging trends: Smarter bioinks, more capable printing hardware, and closer integration of computational design. Because several of the supporting studies in this section concern complex-tissue engineering generally rather than tendon, the current level of evidence is stated explicitly for each strategy, and claims are kept conditional where tendon-specific validation is absent.

Stimulus-responsive (“smart”) bioinks that adapt to mechanical load, temperature, or pH represent an important area of biomaterials research and may improve physiological integration and functional performance[25]. Evidence level: Conceptual proposal for tendon; supporting work derives from other tissues. A related development is the emergence of self-healing hydrogels designed to repair micro-damage within a scaffold, which may be relevant to repeatedly loaded tissues such as tendon[26]. Evidence level: Evidence from other tissues; no tendon-specific in vivo validation.

On the hardware side, multi-material bioprinters permit the deposition of different materials within a single construct, creating opportunities to reproduce the spatial heterogeneity of tendon and tendon-bone interfaces[27]. Evidence level: Tendon-specific in vivo evidence exists for gradient and multilayered constructs[14,19,20], although not for the full range of multi-material platforms. Continued work on vascularisation is likely to remain a central engineering challenge[15]; evidence level for vascular co-printing in tendon: Extrapolated from other tissues.

Computational design and data-driven optimisation are increasingly used to refine scaffold geometry, material distribution, and anticipated mechanical behaviour before printing. Finite element analysis permits the predicted stress and strain distribution within a candidate scaffold to be simulated under physiological loading, so that stress concentrations at suture points or at the tendon-to-bone transition can be identified and the design revised before fabrication. Topology optimisation goes further, iteratively redistributing material to achieve a target stiffness or compliance gradient at minimum material volume, which is directly relevant to reproducing the graded mechanical transition of the enthesis. Algorithm-assisted printing has been used to construct anisotropic biomimetic tissues in which fibre orientation is computationally specified[28], and machine learning approaches to print-parameter selection and in vivo model design have recently been reviewed in the tendon context[6]. Evidence level: Tendon-specific in vitro and computational work exists, but no tendon construct designed by topology optimisation has yet been validated in vivo.

Tendon-specific validation of any of these strategies would require, at minimum: Demonstration of cell viability within the construct beyond the immediate post-printing period; confirmation that any printed vascular patterning persists and anastomoses with host vessels; characterisation of fatigue behaviour under physiological cyclic loading rather than single-pull-to-failure testing alone; and evidence that the regional mechanical gradient of the tendon-to-bone interface is preserved rather than averaged across the construct. Until such data exist, the strategies above should be regarded as plausible directions rather than established techniques[29].

Translating these advances into routine practice will require progress in scalable manufacturing, reproducible quality control, cost-effectiveness, and regulatory pathways. For complex cell-containing constructs, classification, sterility, potency, manufacturing standards, and long-term safety remain important translational considerations[2]. Continued interdisciplinary collaboration among clinicians, bioengineers, materials scientists, and regulators will be necessary before bioprinted tendon constructs can move from experimental studies to routine care (Figure 2).

Figure 2
Figure 2 Workflow for patient-specific three-dimensional bioprinting of tendon constructs. A: Patient imaging; B: Digital modelling and design; C: Biofabrication; D: Construct maturation; E: Surgical implantation. The timeline is not drawn to scale and will vary according to construct complexity and maturation requirements.
CLINICAL AND ECONOMIC IMPLICATIONS

For patients, a potential advantage of bioprinted tendon reconstruction is reduced reliance on donor tissue, thereby avoiding donor-site morbidity and some limitations of graft supply. Bioprinted constructs can also be tailored to an individual defect and designed to approximate aspects of native tendon architecture[2,13]. However, whether this degree of customisation produces better clinical outcomes or faster recovery in humans has not yet been established.

From a health-economic perspective, bioprinting requires substantial upfront investment in equipment, materials, quality assurance, and specialist expertise. A meaningful cost comparison against current practice is not yet possible, because no bioprinted tendon construct has reached routine clinical use and no costed manufacturing pathway has been published. What can be said is where the cost structures differ. Autograft carries no material cost but incurs additional operating time and the downstream costs of donor-site morbidity. Allograft and commercially available acellular dermal or synthetic patches carry a per-unit procurement cost and the overheads of tissue banking. A patient-specific bioprinted construct would instead carry the costs of imaging and digital modelling, bioink and cell sourcing, printing, a period of controlled maturation, and release testing — with cell sourcing and quality control likely to dominate, as they do for other autologous cell-based products. Whether the total exceeds current graft costs is unknown and will depend heavily on whether manufacturing can be centralised.

If bioprinted constructs do prove costly, the rational place to introduce them first is in indications where current outcomes are poor and the cost of failure is high. Massive and revision rotator cuff tears are the clearest example: Retear rates after repair of massive tears remain substantial, revision surgery is expensive, and the functional consequences of failure are significant. In such settings a more expensive construct that reduced retear could plausibly be cost-effective, whereas in routine primary repair with good expected outcomes the economic case would be far weaker. Formal cost-effectiveness analysis will require clinical outcome data that do not yet exist.

Several practical barriers remain before this pathway becomes routine. Regulatory classification is among the most consequential. A printed acellular scaffold may be regulated as a device, whereas the same scaffold printed with living autologous cells is likely to be treated as a cell-based advanced therapy, with correspondingly greater requirements for potency assays, sterility assurance, cell-source governance, comparability between batches, and long-term follow-up. In the United States, products of this kind may be eligible for the Food and Drug Administration’s Regenerative Medicine Advanced Therapy (RMAT) designation, which is available to regenerative medicine therapies intended to treat a serious condition where preliminary clinical evidence indicates potential to address an unmet need; RMAT confers intensified interaction with the agency and eligibility for accelerated approval pathways. The threshold, however, is preliminary clinical evidence — which no bioprinted tendon construct currently has. In the European Union, an equivalent construct would fall within the Advanced Therapy Medicinal Product framework, with its own manufacturing and authorisation requirements. Reproducible manufacturing, sterility, and quality control will be prerequisites under either regime[2].Questions surrounding intellectual property in proprietary bioinks and printing hardware may also influence accessibility and implementation.

Long-term outcome data on immunogenicity, degradation, mechanical durability, and host integration are still needed. Surgical and bioengineering teams will also require dedicated training and validated workflows to integrate this technology safely into clinical practice. These considerations reinforce the current distinction between promising preclinical evidence and established clinical treatment (Table 2).

Table 2 Principal advances and remaining challenges in tendon bioprinting.
Aspect
Advancement
Impact
Bioprinting techniquesExtrusion, laser-assisted, and inkjet approaches with improving control of spatial depositionSupports fabrication of organised tendon-like and interface constructs
Bioink developmentCollagen-, gelatin-, fibrin-, and ECM-derived bioinks combined with synthetic reinforcementBalances biological activity with structural stability
Biological integrationCell-laden and tissue-specific bioinks; ADMSCs and MSCs printed within the bioink; distinguished from constructs seeded after fabricationSupports zonal organisation and tendon-bone interface regeneration in preclinical models
Preclinical evidenceRabbit 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 challengesVascularisation, in vitro mechanical properties, in vivo durability under cyclic loading, reproducibility, scale-upResearch focuses on vascular strategies, robust composite constructs, and reproducible workflows
Clinical and regulatoryClassification as device vs cell-based advanced therapy; potency, sterility and cell-source governance; RMAT and ATMP pathways; cost-effectivenessTranslational barriers distinct from technical ones; no bioprinted tendon construct has yet reached clinical evaluation
CONCLUSION

Over the past decade, 3D bioprinting has developed from a conceptual extension of additive manufacturing into a promising experimental strategy for tendon reconstruction. Advances in bioink chemistry, printing hardware, composite scaffold design, and the incorporation of living cells during printing — as distinct from seeding cells onto pre-printed scaffolds — have enabled constructs that more closely approximate the spatial organisation and functional requirements of native tendon and tendon-bone interfaces.

The next phase of development, encompassing advanced and self-healing bioinks, multi-material printing, vascularisation strategies, and computationally guided scaffold optimisation, must be matched by progress in mechanical durability, reproducible scale-up, regulatory pathways, and cost-effectiveness. Most of these emerging strategies currently rest on evidence from other tissues rather than tendon-specific in vivo validation, and should be described as such. Current evidence remains predominantly preclinical; well-designed translational studies and eventual human clinical evaluation will be necessary to establish safety, durability, and meaningful patient benefit before bioprinted tendon reconstruction can become routine practice.

References
1.  Sharma P, Maffulli N. Tendon injury and tendinopathy: healing and repair. J Bone Joint Surg Am. 2005;87:187-202.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 417]  [Cited by in RCA: 524]  [Article Influence: 25.0]  [Reference Citation Analysis (1)]
2.  Rosset J, Olaniyanu E, Stein K, Almeida ND, França R. Exploring the Frontier of 3D Bioprinting for Tendon Regeneration: A Review. Eng. 2024;5:1838-1849.  [PubMed]  [DOI]  [Full Text]
3.  Murphy SV, Atala A. 3D bioprinting of tissues and organs. Nat Biotechnol. 2014;32:773-785.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 3943]  [Cited by in RCA: 3947]  [Article Influence: 358.8]  [Reference Citation Analysis (5)]
4.  Zhu W, Ma X, Gou M, Mei D, Zhang K, Chen S. 3D printing of functional biomaterials for tissue engineering. Curr Opin Biotechnol. 2016;40:103-112.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 472]  [Cited by in RCA: 482]  [Article Influence: 48.2]  [Reference Citation Analysis (1)]
5.  Bai X, Yang Y, Chu J, Deng Y, Li M, Yang H. 3D bioprinting patient-specific grafts for tendon/ligament repair in motion: emerging trends and challenges. Front Bioeng Biotechnol. 2025;13:1643430.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Full Text (PDF)]  [Cited by in Crossref: 7]  [Cited by in RCA: 4]  [Article Influence: 4.0]  [Reference Citation Analysis (0)]
6.  Lin X, Zhang Z, Zhou T, Li J, Jin Q, Li Y, Guan Y, Xia Y, Zhou X, Fan L. The Role of Computed Tomography and Artificial Intelligence in Evaluating the Comorbidities of Chronic Obstructive Pulmonary Disease: A One-Stop CT Scanning for Lung Cancer Screening. Int J Chron Obstruct Pulmon Dis. 2025;20:1395-1406.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Full Text (PDF)]  [Cited by in Crossref: 1]  [Cited by in RCA: 2]  [Article Influence: 2.0]  [Reference Citation Analysis (0)]
7.  Melchels FP, Feijen J, Grijpma DW. A review on stereolithography and its applications in biomedical engineering. Biomaterials. 2010;31:6121-6130.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 1430]  [Cited by in RCA: 985]  [Article Influence: 61.6]  [Reference Citation Analysis (0)]
8.  Mironov V, Boland T, Trusk T, Forgacs G, Markwald RR. Organ printing: computer-aided jet-based 3D tissue engineering. Trends Biotechnol. 2003;21:157-161.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 969]  [Cited by in RCA: 644]  [Article Influence: 28.0]  [Reference Citation Analysis (1)]
9.  Lee KY, Mooney DJ. Alginate: properties and biomedical applications. Prog Polym Sci. 2012;37:106-126.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Full Text (PDF)]  [Cited by in Crossref: 7096]  [Cited by in RCA: 4797]  [Article Influence: 342.6]  [Reference Citation Analysis (1)]
10.  Guillemot F, Souquet A, Catros S, Guillotin B, Lopez J, Faucon M, Pippenger B, Bareille R, Rémy M, Bellance S, Chabassier P, Fricain JC, Amédée J. High-throughput laser printing of cells and biomaterials for tissue engineering. Acta Biomater. 2010;6:2494-2500.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 316]  [Cited by in RCA: 230]  [Article Influence: 14.4]  [Reference Citation Analysis (0)]
11.  Wang K, Ho C, Zhang C, Wang B. A Review on the 3D Printing of Functional Structures for Medical Phantoms and Regenerated Tissue and Organ Applications. Engineering. 2017;3:653-662.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 138]  [Cited by in RCA: 62]  [Article Influence: 6.9]  [Reference Citation Analysis (1)]
12.  Jiang X, Wu S, Kuss M, Kong Y, Shi W, Streubel PN, Li T, Duan B. 3D printing of multilayered scaffolds for rotator cuff tendon regeneration. Bioact Mater. 2020;5:636-643.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Full Text (PDF)]  [Cited by in Crossref: 50]  [Cited by in RCA: 61]  [Article Influence: 10.2]  [Reference Citation Analysis (0)]
13.  Bertassoni LE, Cardoso JC, Manoharan V, Cristino AL, Bhise NS, Araujo WA, Zorlutuna P, Vrana NE, Ghaemmaghami AM, Dokmeci MR, Khademhosseini A. Direct-write bioprinting of cell-laden methacrylated gelatin hydrogels. Biofabrication. 2014;6:024105.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 491]  [Cited by in RCA: 410]  [Article Influence: 34.2]  [Reference Citation Analysis (0)]
14.  Chae S, Sun Y, Choi YJ, Ha DH, Jeon I, Cho DW. 3D cell-printing of tendon-bone interface using tissue-derived extracellular matrix bioinks for chronic rotator cuff repair. Biofabrication. 2021;13.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 22]  [Cited by in RCA: 62]  [Article Influence: 10.3]  [Reference Citation Analysis (0)]
15.  Kolesky DB, Truby RL, Gladman AS, Busbee TA, Homan KA, Lewis JA. 3D bioprinting of vascularized, heterogeneous cell-laden tissue constructs. Adv Mater. 2014;26:3124-3130.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 1530]  [Cited by in RCA: 1283]  [Article Influence: 106.9]  [Reference Citation Analysis (0)]
16.  Malda J, Visser J, Melchels FP, Jüngst T, Hennink WE, Dhert WJ, Groll J, Hutmacher DW. 25th anniversary article: Engineering hydrogels for biofabrication. Adv Mater. 2013;25:5011-5028.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 1341]  [Cited by in RCA: 1167]  [Article Influence: 89.8]  [Reference Citation Analysis (0)]
17.  Kang HW, Lee SJ, Ko IK, Kengla C, Yoo JJ, Atala A. A 3D bioprinting system to produce human-scale tissue constructs with structural integrity. Nat Biotechnol. 2016;34:312-319.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 1649]  [Cited by in RCA: 1634]  [Article Influence: 163.4]  [Reference Citation Analysis (12)]
18.  Hospodiuk M, Dey M, Sosnoski D, Ozbolat IT. The bioink: A comprehensive review on bioprintable materials. Biotechnol Adv. 2017;35:217-239.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 623]  [Cited by in RCA: 664]  [Article Influence: 73.8]  [Reference Citation Analysis (3)]
19.  Jiang X, Kong Y, Kuss M, Weisenburger J, Haider H, Harms R, Shi W, Liu B, Xue W, Dong J, Xie J, Streubel P, Duan B. 3D bioprinting of multilayered scaffolds with spatially differentiated ADMSCs for rotator cuff tendon-to-bone interface regeneration. Applied Materials Today. 2022;27:101510.  [PubMed]  [DOI]  [Full Text]
20.  Chae S, Yong U, Park W, Choi YM, Jeon IH, Kang H, Jang J, Choi HS, Cho DW. 3D cell-printing of gradient multi-tissue interfaces for rotator cuff regeneration. Bioact Mater. 2023;19:611-625.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Full Text (PDF)]  [Cited by in Crossref: 1]  [Cited by in RCA: 33]  [Article Influence: 11.0]  [Reference Citation Analysis (1)]
21.  Kim W, Kwon DR, Lee H, Lee J, Moon YS, Lee SC, Kim GH. 3D bioprinted multi-layered cell constructs with gradient core-shell interface for tendon-to-bone tissue regeneration. Bioact Mater. 2025;43:471-490.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Full Text (PDF)]  [Cited by in RCA: 14]  [Reference Citation Analysis (0)]
22.  Zhang X, Wu Y, Han K, Fang Z, Cho E, Hu Y, Huangfu X, Zhao J. 3-Dimensional Bioprinting of a Tendon Stem Cell-Derived Exosomes Loaded Scaffold to Bridge the Unrepairable Massive Rotator Cuff Tear. Am J Sports Med. 2024;52:2358-2371.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in RCA: 12]  [Reference Citation Analysis (0)]
23.  Kaneda G, Chan JL, Castaneda CM, Papalamprou A, Sheyn J, Shelest O, Huang D, Kluser N, Yu V, Ignacio GC, Gertych A, Yoshida R, Metzger MF, Tawackoli W, Vernengo A, Sheyn D. iPSC-derived tenocytes seeded on microgrooved 3D printed scaffolds for Achilles tendon regeneration. J Orthop Res. 2023;41:2205-2220.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 1]  [Cited by in RCA: 10]  [Article Influence: 3.3]  [Reference Citation Analysis (0)]
24.  Liu X, Cen Y, Zhang W, Tian K, Yuan F, Wang X. Trifecta of Tendon Regeneration: 3D Bioprinted Scaffolds Recapitulate Hierarchical Interfaces From Muscle-to-Bone. Adv Healthc Mater. 2026;15:e03063.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 1]  [Cited by in RCA: 3]  [Article Influence: 3.0]  [Reference Citation Analysis (1)]
25.  Dvir T, Timko BP, Kohane DS, Langer R. Nanotechnological strategies for engineering complex tissues. Nat Nanotechnol. 2011;6:13-22.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 1157]  [Cited by in RCA: 830]  [Article Influence: 55.3]  [Reference Citation Analysis (1)]
26.  Zhang YS, Khademhosseini A. Advances in engineering hydrogels. Science. 2017;356:eaaf3627.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 1886]  [Cited by in RCA: 1611]  [Article Influence: 179.0]  [Reference Citation Analysis (0)]
27.  Jung JW, Lee JS, Cho DW. Computer-aided multiple-head 3D printing system for printing of heterogeneous organ/tissue constructs. Sci Rep. 2016;6:21685.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Full Text (PDF)]  [Cited by in Crossref: 70]  [Cited by in RCA: 67]  [Article Influence: 6.7]  [Reference Citation Analysis (0)]
28.  Li C, Chen J, Jie T, Wu W, Wang K, Wang J, Deng L, Wang B, Cui W. Construction of Biomimetic Tissues with Anisotropic Structures via Stepwise Algorithm-Assisted Bioprinting. Small. 2022;18:e2204316.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 5]  [Cited by in RCA: 2]  [Article Influence: 0.5]  [Reference Citation Analysis (0)]
29.  Seol YJ, Kang HW, Lee SJ, Atala A, Yoo JJ. Bioprinting technology and its applications. Eur J Cardiothorac Surg. 2014;46:342-348.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 308]  [Cited by in RCA: 180]  [Article Influence: 15.0]  [Reference Citation Analysis (0)]
Footnotes

Peer review: Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Orthopedics

Country of origin: United Kingdom

Peer-review report’s classification

Scientific quality: Grade B, Grade B, Grade B

Novelty: Grade B, Grade B, Grade C

Creativity or innovation: Grade B, Grade B, Grade C

Scientific significance: Grade A, Grade B, Grade B

P-Reviewer: Fu L, Associate Professor, PhD, China; Wang K, PhD, Senior Research Fellow, Senior Researcher, United States S-Editor: Liu JH L-Editor: A P-Editor: Lei YY

Write to the Help Desk