Engineered Vascular Entities
Evolving 3D Printed Blood Vessels
A 3D bioprinting process is being used to create blood vessels that closely replicate human vasculature. This framework that facilitates the printing of complex, multilayered vascular networks was engineered by the Harvard Wyss Institute. Constructed from the basis of their first SWIFT method, researchers launched the co-SWIFT method which improved overall functionality. While this technology is groundbreaking and opens many doors for the future of drug testing, individualized designs and other pivotal developments, some challenges such as long-term viability, scaling, and integration of these vessels are still being resolved.
Bioprinting research and tissue engineering attempts kicked off in the early 2000s, but without adequate technology and knowledge, this was to minimal avail. In 2010, sacrificial printing developed the first structures for tissue engineering on a small scale. At this time, 3D printing technologies could not accurately mimic the material properties within the complexity of blood vessels. In the mid 2010s, the debut of SWIFT (Sacrificial Writing into Functional Tissues) was accompanied by advancements in tissue creation, specifically 3D printing of functional vascularized tissues. Sacrificial materials, those that can be retracted after printing, were used to form channels within the printed tissues, further allowing those channels to be filled with substances and leading to the replication of the human vascular network. In the early 2020s, Co-SWIFT a secondary, more improved method of SWIFT evolved. The primary advancement of this new technology is the coaxial printhead design used to print branched, multilayered vascular structures. (Stankey et al., 2024) Co-SWIFT allows for the creation of sophisticated tissues that are embedded with smooth muscle and endothelial cells. Furthermore, specialized bioinks which contain living cells and the development of a precise bioprinting platform that warranted accurate deposition of those bioinks has contributed to the development of 3D printed blood vessels.
Prior to Co-SWIFT, the hierarchical structure of human blood vessels was not able to be properly replicated with traditional tissue engineering. Researchers effectively reconstructed the architecture of human blood vessels, which have an inner layer of endothelial cells and an outer layer of smooth muscle cells, through printing branched vascular networks with multiple layers. Co-SWIFT’s technology created vessels that mirror real blood flow, grant proper nutrient and oxygen distribution, transport fluids, contract and dilate - all while remaining perfusable. The incredibly realistic biomechanical properties of these vessels does not stop there, they can also withstand blood pressure and demonstrate elasticity, in turn leading to the prevention of ruptures, collapse and blockages. Breakthroughs in the utility of bioinks has dramatically assisted in the framework of 3D printed blood vessels. Bioinks are synthesized to emulate the extracellular matrix (ECM) of natural tissues. A collaboration of decellularized ECM, synthetic polymers (polyethylene glycol, Pluronic F127, methacrylated gelatin), and natural hydrogels (collagen, fibrin, gelatin) is used to diversify the elasticity, durability and stiffness of printed vascular structures. The differentiating properties of bioinks correlate to each layer of printed blood vessels and their integration with circumferential tissues. (Brownell, 2024) Printed vessels are composed of flexible capillaries (endothelial layer) using soft bioinks, veins (smooth muscle layer) containing a combination of soft/stiff bioinks, and arteries (connective tissue layer) constructed of stiff bioinks. Cell migration is promoted by soft bioinks whereas bioinks that are too stiff inhibit cell growth. Additional efficacious breakthroughs include the ability to keep large tissue volumes alive ex vivo while maintaining proper nutrient and oxygen distribution, improved longevity of tissues, and potential scalability.
The advancement of 3D printed blood vessels is adaptable, which positively impacts the developments of 3D printed organs and vessels for specific tissues or organs in individuals, allowing for remarkable personalized treatments. Pharmaceutical companies, medical researchers, hospitals, and organ transplantation programs can use this technology to explore diseases, assist blood transfusions, and test new drugs, therapies, and vaccines. The use of autologous cells assists in optimizing personalized surgical methods, treatments and drugs, in turn reducing the risk of immune rejection in terms of organ transplants. If used appropriately this patient-centered approach has an enormous impact on medical care. Pharmacogenomics is also impacted regarding more accurate doses, prevention of negative side effects, utilization of combination mechanisms, and an overall improvement of safety and effectiveness of drugs. In vitro testing displays a patient’s vascular system and can be done to determine metabolization of drugs, toxicity, and bioavailability. Since this advancement is adaptable, the tie in of pharmacogenomics has the potential to develop a personalized long-term plan, not just for a patient, but also for their offspring. When looking at 3D printed blood vessels from an ethical perspective, the need for animal testing is decreased, clinical trials are safer, organ harvesting would decrease and transparency within healthcare would increase. Cost-effectiveness is impacted from the decrease of preclinical testing costs, a reduction of large clinical trials, and more reliable organ transplants. Moreover, further development of smart, shear-thinning, self-healing, and patient-specific bioinks which display positive changes regarding responses to blood flow, repairing micro-damage, and reductions in immune rejections are additional advantageous impacts.
Operational boundaries and theoretical cellular barriers with respect to bioinks, vascularization, biopsies, and tissue survivability are among the impediments revolving around 3D printed vascular systems. Some technical complexities include compatibility of bioinks, proper perfusion and nutrient distribution, geometric structure in regards to topographical organization, and adaptive capacity and cultivation of 3D printed vessels. Biological constraints subsume negative immune reactions, complications in attempts to recreate the ECM leading to fast tracked degradation of printed tissues and deferred maturation. The flux into clinical uses from bioprinting in a lab is another challenge of this technology. Since this is a relatively new development, protocols and regulations are not firmly written out and researchers have yet to determine long-term effects. Additional apprehensions around bioengineering ethics, costs of bioprinters and bioinks, patents, future accessibility and scalability also arise with this product.
Pertaining to the disciplines of regenerative medicine and tissue engineering, the latent capacity of 3D printed blood vessels developed by the Harvard Wyss institute denote a revolutionary leap forward. Though challenges are scattered across economic, technical, biological, and regulatory fields, 3D bioprinting still holds a massive potential to transform medicine, healthcare, drug testing and more. Establishing regulatory scaffolds and protocols, improving biocompatibility of bioinks, and enhancing the development of bioprinting technology will contribute to proper evolution of 3D printed vascular models. In encapsulation, this technology carries a weight of transformative advancement along with a need to embody adept handling of scientific impediments.
References
Brownell, L. (2024, August 7). 3D-printed blood vessels bring artificial organs closer to Reality.
https://wyss.harvard.edu/news/3d-printed-blood-vessels-bring-artificial-organs-closer-to-reality/
Choi, J., Lee, E. J., Jang, W. B., & Kwon, S.-M. (2023, October 8). Development of
biocompatible 3D-printed artificial blood vessels through multidimensional approaches.
Pub Med Journal of functional biomaterials. https://pubmed.ncbi.nlm.nih.gov/37888162/
Biocompare. (2024, August 7). Harvard team develops method to 3D print blood vessels .
Charuchandra, S. (2024, September 11). 3D printing creates human-like blood vessels in heart
tissue. https://www.advancedsciencenews.com/3d-printing-creates-human-like-blood-vessels-in-heart-tissue/
Chavez, E. (2024, August 23). 3D-printed blood vessels? Harvard’s one step closer to artificial
Stankey, P. P., Kroll, K. T., Ainscough, A. J., Reynolds, D. S., Elamine, A., Fichtenkort, B. T.,
Uzel, S. G. M., & Lewis, J. A. (2024). Embedding biomimetic vascular networks via
coaxial sacrificial writing into functional tissue. Wiley Advanced Materials.
