Abstract

Biofabrication has emerged as an attractive strategy to personalise medical care and provide new treatments for common organ damage or diseases. While it has made impactful headway in e.g., skin grafting, drug testing and cancer research purposes, its application to treat musculoskeletal tissue disorders in a clinical setting remains scarce. Albeit with several in vitro breakthroughs over the past decade, standard musculoskeletal treatments are still limited to palliative care or surgical interventions with limited long-term effects and biological functionality. To better understand this lack of translation, it is important to study connections between basic science challenges and developments with translational hurdles and evolving frameworks for this fully disruptive technology that is biofabrication. This review paper thus looks closely at the processing stage of biofabrication, specifically at the bioinks suitable for musculoskeletal tissue fabrication and their trends of usage. This includes underlying composite bioink strategies to address the shortfalls of sole biomaterials. We also review recent advances made to overcome long-standing challenges in the field of biofabrication, namely bioprinting of low-viscosity bioinks, controlled delivery of growth factors, and the fabrication of spatially graded biological and structural scaffolds to help biofabricate more clinically relevant constructs. We further explore the clinical application of biofabricated musculoskeletal structures, regulatory pathways, and challenges for clinical translation, while identifying the opportunities that currently lie closest to clinical translation. In this article, we consider the next era of biofabrication and the overarching challenges that need to be addressed to reach clinical relevance.

Highlights

  • The musculoskeletal system, consisting of different types of bones, muscles, ligaments and tendons, is one of the key systems in the human body

  • We mainly explore neitysynthetic in cellular structural properties, it becomes that forcomposite a successful tissue enandand natural bioinks before discussing theclear underlying bioink strategies gineering approach, the fabrication technique needs to recapitulate the compositional, meto address the shortfalls of sole biomaterials

  • It is clear that many biomaterials have become well characterised and validated so that their advantageous properties can be harnessed across several platforms

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Summary

Introduction

The musculoskeletal system, consisting of different types of bones, muscles, ligaments and tendons, is one of the key systems in the human body. Advances in additivenamely manufacturing have of overcome long-standing challenges in the field of biofabrication, the bioprinting opened new possibilities to fabricate structures with synergistic biological and mechanical low-viscosity bioinks, controlled delivery of growth factors, and the fabrication of spatially properties can mimic natural scaffolds tissue structures. Extrusion-based bioprinting is operationally more adoptable with respect to printing multiple biomaterials and cell types and it has opened new ways to fabricate complex tissues and organs [37] This technique has been used widely to create hybrid and composite structures in order to have both hydrogels and synthetic polymers in one structure; hydrogel creates a cell-friendly environment used for drug-delivery purposes and growth factor/cell incorporation, while a synthetic polymer is used to enhance the mechanical properties due to the poor mechanical characteristics of hydrogels. Has steadily moved from single component bioink formulations to more complex more complex multicomponent structures (D)

Designing Musculoskeletal Bioinks
Synthetic Materials
Natural Materials
Composite Materials
Functional Properties and Clinical Challenges of Musculoskeletal Bioinks
Low-Viscosity Bioinks
Controlled Delivery of Growth Factors and Cells
Hierarchical Structures
Challenges
Regulatory Classifications and Governing Bodies
Translational Pathways
Sterilisation
In Vitro Evaluation
In Vivo Evaluation
Premarket Evaluation
Clinical Trials
Other Considerations
Current Examples of Clinical Applications
Findings
Conclusions and Future Perspectives
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