Introduction

The complex swath of blood vessels in the body carry oxygen and nutrients to the body's tissues and eliminate waste products. Getting a handle on the architecture of arteries is key to studying many disease states such as cardiovascular disease, cancer and regeneration of tissue. The classical approach to the study of vascular networks can go only so far, as it doesn't always accurately describe the complexity of three-dimensional (3D) structures. But 3D printing has now allowed us to create intricate vascular micro-models in a way that's never been possible before, and which will reveal something new about vascular biology, and enable the design of advanced medical treatments. In this paper, we cover the theory, uses and prospects of complex vascular micro-model 3D printing.

Figure 1. Vascular network formation on the 3D cell printed vascular platform (VP).( Chen EP, et al.; 2021)

The Need for Vascular Micro-models

It has never been easy to study vasculature in vitro because blood vessels are, as a rule, complex and fragile. Even conventional methods (such as 2D cell cultures and animal models) are usually unable to approximate the real 3D structures and physiology of the human vasculature. This difference can be misinterpreted in predicting the anatomy of blood vessels within the human body and therefore prevent the formulation of effective medicines for vascular diseases.

Intricate micro-models of the vascular system that are 3D printed fill this gap by giving a more accurate model of vascular architecture. These can model the vascular structure in a hierarchical fashion, from massive arteries to small capillaries, and be adapted to mimic disease states or patients' vascular anatomy.

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3D Printing Physiology Vascular Micro-models Principles 3D Printing Basics

Adding to this, 3D printing or additive manufacturing is the deposition of materials in layers to form 3D structures according to digital models. 3D printing vascular micro-models typically has a few main steps:

1. Design and Modeling

CAD programs make a digital image of the vascular architecture first. This can be a medical image-based model, derived from computed tomography (CT) or magnetic resonance imaging (MRI) scans, or it can be made to simulate vascular states.

2. Material Selection

It's important to choose the right materials when preparing functional vascular models. Hydrogels, biocompatible polymers and living cell-based bioinks are all used. These materials have to replicate the mechanical and biological features of natural blood vessels and promote cell growth and proliferation.

3. 3D Printing Process

The 3D bioprinter prints the digital replica, and sinters the material of choice layer by layer to construct the vascular organ. With more advanced 3D bioprinters, one can control the layers of a single material precisely to build multi-layered vascular structures.

4. Post-Processing and Maturation

The vascular template might need some post-printing crosslinking or curing to make it more mechanically stable. The model is also generally grown in bioreactors to allow the cells to grow and mature so that printed blood vessels have functional functions, just like real blood vessels.

3D Printing Uses in Vascular Research and Healthcare

The possibility of 3D printing elaborate micro-models of vascular structures is transformative for fundamental science and clinical use. These are just a few of the areas where these models are really impacting:

.1 Disease Modeling and Drug Testing

Vascular conditions like atherosclerosis and aneurysms are hard to research by classical methods. These diseases are reproducible in a laboratory setting using 3D-printed vascular models, which researchers can use to study disease progression and trial new therapies. These models can also be used to test vascular-targeted drugs' efficacy and safety, eliminating animal models and accelerating drug development.

2. Tissue Engineering and Regenerative Medicine

Developing active vascular systems is a huge challenge in tissue engineering and regenerative medicine. Vessel models 3D-printed can be added to tissue designed for the same purposes to supply a blood flow, thus maintaining tissue function and life. This could change the face of organ transplantation by allowing us to build bioengineered organs with their own blood supply, eliminating transplant rejection and immunosuppressive drugs.

3. Personalized Medicine

Vascular models can be built from medical images of patients for individual treatment planning and surgery training. Surgeons could, for instance, 3D-print models for complex vascular procedures or to place stents and grafts as specific as the anatomy of each patient. This individualised intervention can aid in a better outcome of surgery and fewer complications.

4. Cancer Research

The expansion and spread of tumours depends heavily on new blood vessels (angiogenesis). You can also model vascular systems 3D-printed to observe how tumors work with the blood vessels, and learn how cancer cells hijack the vascular network to feed themselves. We can even use these models to investigate anti-angiogenic drugs, designed to starve tumours by suppressing blood vessel formation.

Challenges and Future Directions

While vascular micro-models can be 3D printed in a very advanced manner, there are still some obstacles:

• Material Limitations: The pursuit of materials that accurately resemble the mechanical and biological aspects of the natural blood vessels is not a walk in the park. Biomaterials science has to improve for more multifunctional bioinks.
• Vascular Complexity: To replicate the full extent of the vascular network, from the branching paths to blood vessel diameters, prints have to be extremely detailed. There is still room for 3D printing to advance even more in both quality and resolution.
• Functional Compatibility: 3D-printed vascular systems must be fully integrated and function within living tissue to make them work is a huge challenge. This kind of research on optimizing the interaction between printed vessels and host tissue is fundamental to the success of tissue-engineered systems.

As for the future, 3D printing in combination with other technology, like microfluidics and digital imaging, could expand vascular models. By using 3D printing and microfluidics, for instance, dynamic models of blood circulation and shear stress can be created, giving more physiologically based experimental conditions to study vascular biology.

Conclusion

Complex vascular micro-model 3D printing has been a game changer for vascular research and medicine. With precise, customizable models of the vascular system, this technology is changing how we study vascular disease, create new cures, and transform tissue engineering. The road is not over yet, but advancements in 3D printing, biomaterials and tissue engineering promise to circumvent it, making way for more advanced and functional vascular models. This technology will only improve over time and the impact on vascular research and clinical practice will likely be immense, providing hope for patients suffering from vascular disorders and deepening our understanding of one of the most important systems of the body.

Reference

1. Chen EP, et al.; 3D Bioprinting of Vascularized Tissues for in vitro and in vivo Applications. Front Bioeng Biotechnol. 2021, 9:664188.