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International Journal of Bioprinting dECM bioink for in vitro disease modeling
nerve bundle, the CNSdECM can support neurons more body. The vascular conduits and contractile tissues are
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as they grow and secret new ECMs, as opposed to Matrigel, interconnected with high complexity and heterogeneity. The
which is degradable and not able to maintain the structural vascular network delivers oxygen, nutrients, metabolites,
integrity. Moreover, 3D bioprinting-based models have the and blood. Arteries transport oxygen-rich blood from the
advantage of realizing the engineered design of the tissue heart to other organs, whereas veins deliver metabolites
analog, which is similar to the native tissue structure. to organs and tissues such as kidney and liver. Capillaries
Conventional methods are limited to building 2D are also involved in substance transport, mediated by
structures and structures naturally generated from cellular diffusion through thin endothelia. The heart acts as a
differentiation. The 3D bioprinting structure in adherence pump to induce blood flow. Thus, any disruptions to the
with the engineer’s design, which is intended to enhance structural integrity and functions of cardiovascular tissue
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the physiological resemblance to native tissues, is feasible. place an obstacle to substance circulation in the body.
However, the current nervous system models require One of the most prominent conditions associated with
improvement with regard to precise control of neuronal CVDs is atherosclerosis, which occurs as a result of plaque
direction and maturation. The technical limitations can be formation in the arterial walls due to high cholesterol and
overcome by applying various 3D bioprinting methods and triglyceride levels. The development of atherosclerosis is
incorporating nervous tissue-specific dECMs and specific also closely related to the alterations in hemodynamics,
components of the dECM. 85,148 For example, the BBB—a which can be affected by changes in vascular geometry.
brain-specific vascular structure—plays an essential role in Numerous experimental cardiac tissue models are
the CNS as an innate barrier with selective permeability available for clarifying the mechanisms behind cardiac
to prevent penetration of foreign material. Owing to the diseases. Generally constructed on Transwell inserts,
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tightly impregnable layer of endothelial cells in the BBB, traditional in vitro 2D vessel models, which belong
most drug molecules as well as pathological factors cannot to the category of cardiac tissue models, allow for the
penetrate into the neural tissue. Thus, it is necessary to observation of material penetration from one side to
develop BBB-incorporated neural tissue models (i.e., other side in the endothelial layer. These models have
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neurovascular unit models), which can be utilized in contributed to our understanding of transport through
studies for deciphering the penetration mechanism, and the endothelium. Additionally, 2D cardiac models have
to identify a proper strategy for transporting drugs to the been used to investigate cardiac myocyte behavior in
brain. For this, a vascular structure can be added to the in cellular models. However, the limited geometry of the
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vitro neural model via 3D bioprinting. 3D bioprinting has models constrains their usefulness in the delineation of
potential for building various tubular structures for vessels vascular and cardiac physiology, which are related to the
and adapting different cell types for reconstructing complex geometry and mechanical properties of cardiac tissue.
organ systems. Thus, 3D-bioprinted neurovascular unit Furthermore, the hemodynamic mechanism in vessels
models, integrating the BBB and neural tissues, should has not been sufficiently elucidated from the viewpoint of
be constructed to aid elucidation of the crosstalk between biomechanical-therapeutic interplay. Thus, the mimicking
neural cells and BBB. potential of conventional microfluidic vascular models is
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Furthermore, additional bioreaction can support limited to the recapitulation of various vascular geometries,
the recapitulation of the complex structure of central which is not feasible for clarifying CVD mechanism. To
nervous tissue, such as the aligned neural network. The overcome this limitation, recapitulation of 3D geometry
directionally controlled neural network is important for has attracted attention. For example, Gao et al. suggested
elucidating neural signal transduction in the CNS. In the use of vascular tissue-derived dECM (VdECM)-based
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addition, 3D-bioprinted neural models incorporated with arteries in atherosclerosis modeling (Figure 3C). The
electrical sensors and reactors, such as microelectrode VdECM has shown favorable effects on the angiogenesis
arrays, can widen the applicability of in vitro models in the and proliferation of endothelial cells by supporting the
context of healthy and pathological signal transduction in expression of cell–ECM attachment factors (e.g., vascular
the CNS. 151 endothelial [VE]-cadherin, integrin beta-1), as reported in
various studies. By capitalizing on these vascular-related
4.2. Cardiovascular tissue-derived decellularized advantages, Gao et al. developed a vessel structure using
extracellular matrix triple coaxial printing with VdECM. To simulate the
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Cardiovascular disease (CVD) is a chronic and difficult-to- heterogeneity of the arterial structure, smooth muscles cells
cure illness with the highest mortality rate in the world. 152,153 (SMCs) and endothelial cells (ECs) were employed in the
The cardiovascular system consists of the heart, arteries, triple coaxial printing. The geometry of the three-layered
veins, and capillaries that circulate blood throughout the artery is adjustable; modifications can give rise to regular,
Volume 10 Issue 2 (2024) 145 doi: 10.36922/ijb.1970

