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International Journal of Bioprinting Printed organoids for medicine

tissues that can self-assemble into cell aggregates and sprouting. These constructs promote osteogenic
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organoids in response to physiological and induced differentiation and support fracture repair mechanisms.
signals. 11,12 They also help in evaluating the effectiveness However, challenges persist in replicating the
of pharmacological treatments aimed at improving bone hierarchical mechanical properties of native hard tissues,
density and reducing fracture risk.
particularly in achieving stiffness values that match
Bioprinting has been instrumental in engineering hard those of human bones (10–30 GPa) while maintaining
tissue, where the fabrication of a bone extracellular matrix cell viability. Innovations in nozzle-free bioprinting
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(ECM) analog has been achieved to properly mimic the techniques, which eliminate shear stress on encapsulated
3D-mineralized ECM components. This approach enables cells, have improved organoid post-printing viability
precise spatial control over osteogenic cell populations, (>95%) and preserved multicellular polarization. 25,26 De
thereby inducing specific cell fates and functions 13,14 and Leeuw et al. found that elevated cellular density increases
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facilitating the maturation of bone organoids. Bioprinting the rates of mineralization and enhances the mechanical
enables precise manipulation of biophysical properties, stiffness of 3D-bioprinted patient-derived bone organoids
including organoid size, cell number, and conformation, when exposed to dynamic loading conditions. The present
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with modifications in organoid conformation substantially research on bone organoids is in its early developmental
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increasing secreted yield per initial cell number. Rooted phase. These organoids currently emulate only limited
in synthetic biology, recent advancements in light-based aspects of bone tissue functionality. Beyond the standard
3D printing of DNA hydrogels offer promising potential functionalities and essential characteristics of organoids,
to revolutionize current ECM-assembling approaches. bone organoids must replicate both the micro- and macro-
These hydrogels offer key advantages, including resistance architectures of bone tissue. They should also offer sufficient
to enzymatic degradation, programmability, precise mechanical support and incorporate a bone marrow
structural control, and desirable mechanical properties. 17 microenvironment capable of hematopoietic activity.
Recent advances in bioink design, including gelatin Furthermore, bone organoids are expected to produce
methacrylate/alginate methacrylate/hydroxyapatite immune cells and establish functional interactions with
(GelMA/AlgMA/HAP) composites, have facilitated the the nervous, immune, lymphatic, and vascular systems.
creation of self-mineralizing scaffolds that support long- These attributes will facilitate the ability of bone organoids
term maturation of bone organoids. Utilizing cutting- to more accurately replicate the physiological functions of
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edge 3D bioprinting technology and bone matrix-inspired native bone tissue. Other directions include integrating
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bioink formulations, researchers have developed a platform patient-specific stem cells, osteogenesis under compressive
for generating bone organoids from bone marrow- stimulation, and computational modeling to optimize
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derived mesenchymal stem cells. This method involves printed scaffold porosity and load-bearing capacity for
combining bone marrow-derived mesenchymal stem cells clinical translation. 10,29–31
with hydrogels to create bioinks, which are then employed
in light-curing 3D bioprinting to produce bone organoids 2.2. 3D reconstruction of biomimetic
(Figure 2A). Upon implantation into an animal model, cardiovascular organoids
these organoids exhibited spontaneous mineralization and A 3D culture system for cardiomyocytes can replicate
maturation processes, leading to the formation of fully physiological and dynamic conditions effectively for
developed and vascularized bone tissue (Figure 2B). 20,21 cardiovascular assessment. 32,33 The 3D system addresses
Li et al. added hydroxyapatite nanowires to osteoblast limitations seen in 2D monolayer setups, such as
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precursor cell spheroids, providing numerous material inadequate spreading size, excitation-contraction
exchange channels for internal cells by interpenetrating coupling (T-tubules), mature calcium ion channels for
them into cell spheroids. The incorporation of nanowires active force stimuli, and efficient energy conversion
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enhanced the osteogenic phenotype and effectively through oxidative metabolism. Cardiomyocytes and
improved the biological activity of core cells in spheroids, other cardiac cells are cultured within solid biomaterials
which can potentially be used as building blocks for (like scaffolds or hydrogels) in this microenvironment to
the construction of large, high-density biomimetic enhance cardiac tissue formation and simulate the heart’s
tissues and organoids using 3D bioprinting technology physiological conditions. 35,36 The geometric morphology of
(Figure 2C). Fang et al. successfully printed highly cardiomyocytes, myofibril expression, and junction protein
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vascularized bone organoid tissues using a granular formation differ significantly between 3D and 2D cell
aggregate-pre-vascularized bioink and found that the cultures. Furthermore, 3D culture offers cardiomyocytes
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pre-vascularized mesenchymal spheroids developed an protection against drug-induced mechanical stress and
interconnected vascular network through angiogenic apoptosis. Recently, organoids have been developed
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Volume 11 Issue 4 (2025) 69 doi: 10.36922/IJB025190184