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International Journal of Bioprinting Bottom-up and top-down VAT photopolimerization

effects. In this sense, musculoskeletal on-a-chip is a novel still required on various features of the musculoskeletal
and promising technology that can be used to evaluate on-a-chip model. For example, complex joint on-a-chip
the safety and effectiveness of drug and therapeutic systems must be able to recreate the joint cartilage and
development, enlightening the execution of clinical trials. the subchondral bone, synovial fluid, and associated
Considering the number of new cases diagnosed and the vascularized tissues to simulate transport of nutrients, in
direct and indirect costs associated with their treatment, the vivo loading, and inflammation [56-57] . Highly organized
economic impact of on-a-chip models on the biomedical muscle fibers are another example of the complex
field is very high since this new technology allows for microarchitectural engineering required to model
the screening of new, more effective drugs against these innervated tissues. Biological interfaces and ECM
diseases, and the application of personalized medicine gradients are essential for recreating mechanical and
can shorten the treatment times and reduce the different cellular functions and signaling. For example, migration of
problems associated with the use of generalized drugs. In immune cells from the bone marrow into the vasculature
this study, we present a multi-material musculoskeletal (the infiltration of platelets, neutrophils, macrophages),
model made using three different cell types incorporated in migration of various immune cells to sites of tissue injury,
a GelMA 3%/PEGDA 15%/LAP 0.1% bioink formulation. and cancer metastases underline the importance of
The concentration of PEGDA was kept at the lowest engineering vascular barriers [58,59] .
experimental value presented, in order to avoid cell toxicity
associated with higher PEGDA concentrations . Based Without new technologies contributing to the reduction
[36]
on the results of the mechanical tests, a sufficiently stiff of investment risks associated with new drug development,
bioink (between ~20 kPa and ~870 kPa) could be obtained these challenges will not be overcome, and new
with this bioink formulation (PEGDA/GelMA/LAP) applications will deviate from translational efforts. Recent
whose stiffness values are comparable to that reported for advances in 3D bioprinting have allowed the fabrication
vascular and muscle tissues [48-49] . of complex structures and tissues with controlled
[47]
architectures. As a result, there is growing interest in
Despite of the potential of organ-on-chip models in adopting these technologies in emerging areas that need a
imitating various tissues and organs [50,51] , musculoskeletal highly organized construct of biofabrication, such as tissue
on-a-chip platforms have been evolving slowly compared engineering and, in particular, more realistic modeling of
with on-a-chip platforms for other tissue types [52,53] . The the musculoskeletal tissue microenvironment [60,61] . Such
slow adoption of musculoskeletal on-a-chip platforms bioprinted musculoskeletal on-a-chip approaches are ideal
in studies of musculoskeletal pathologies can be due to the following advantages: (i) the use of the patient’s
associated with the conceptual and practical challenges cells; (ii) the small size of the system; (iii) the small amount
in modeling the different cell types, extracellular matrix of tissue required for analysis; (iv) short development time
(ECM) interactions and in vivo mechanical loadings; (1–2 weeks); (v) low-cost manufacturing; (vi) scalability
the lack of innervation and vascularization; and the for high-throughput screening (HTS) testing; and (vii) the
effective recapitulation of complex soft-to-hard tissue decrease in the use of experimental animals.
interfaces. 3D collagen scaffolds have been reported
as a candidate model; however, they typically include 5. Conclusion
a single cell type and fail to closely recapitulate the
heterogeneity of the musculoskeletal tissue [54] . The major In this work, we developed a dual bottom-up and top-
challenges associated with mimicking the physiology down bioprinter, which was demonstrated to be a versatile
of the musculoskeletal on-a-chip have been identified, and powerful tool for 3D bioprinting soft and hard
including incorporation of biological barriers and biomaterials, independently or simultaneously. The new
simulation of joint compartments and heterogeneous bioprinter also allowed to manufacture of high-resolution
tissue interfaces. Overcoming these challenges will tissue models, showing potential for the biofabrication of
revolutionize musculoskeletal research by enabling 3D multi-material and tissue interface structures.
physiologically relevant, predictive models of human Such biofabrication workstation offers several
tissues and joint diseases to accelerate and de-risk innovations. First, a dual-printer configuration allows for
therapeutic discovery and translation to the clinic [55] . greater control of the mechanical and physical properties,
Additionally, to address the challenges of creating such as density, viscosity, or permeability. Second, having
(clinically relevant) disease model on-a-chip with control over the complete process, it was possible to bioprint
the associated biomarkers that can recapitulate the multi-material tissue structures using different hydrogels,
dynamic nature of tissue and chronic pathologies in the allowing for greater precision in achieving tissue interface
musculoskeletal system, new engineering innovations are constructs and hard scaffolds that can be incorporated into

Volume 10 Issue 2 (2023) 540 doi: 10.36922/ijb.1017