New nanoengineered bioinks accelerate functional blood vessel bioprinting

bioprinted blood vessels model human disease

Date: 19th August 2021

3D bioprinting holds much promise for regenerative medicine, addressing the urgent need for tissues and organs suitable for transplantation, but its use extends beyond that for example tissue modelling for research, drug discovery and toxicology.  A major limitation for bioprinting has been supporting the formation of complex-shaped arrangements and the retention of shape for these bioprinted constructs.  The inclusion of blood-vessel like structures which support cell or tissue viability is particularly challenging, and current bioinks lack the necessary properties to achieve this.  Now, researchers have developed a new class of nanoengineered hydrogel-based cell-laden bioinks to 3D print multicellular blood vessels which recapitulates both the physical and chemical microenvironments of native human vasculature.

3D bioprinting is an emerging additive manufacturing technique to fabricate constructs for human disease modelling and ultimately for organ or tissue replacements to treat disease and injury. However, current cell-laden bioinks lack sufficient biocompatibility, printability, and structural stability needed to translate this technology to preclinical and clinical trials. One such area of research with high clinical burden but slowing drug advancement is cardiovascular research.  Vascular disease such as aneurysms, peripheral artery disease and clots inside blood vessels account for over 30% of global deaths.  However, the translation of potential therapeutics into approved methods has been lacking in part due to discrepancies between in vitro modelling and the in vivo environment.

Now, researchers at Texas A&M University, US, led by Akhilesh Gaharwar and Abhishek Jain, have designed a 3D-bioprinted model of a blood vessel that mimics the native vascular function and disease response using a new nanoengineered bioink.

The team developed the new class of nanoengineered hydrogel-based cell-laden bioinks to overcome the shortcomings of the current bioinks.  The nanocomposite bioink had a unique but remarkable property that regardless of cell density, it still remained highly printable, and could protect the encapulsated cells against the high shear forces that occur during the bioprinting process. By investigating the interactions between individual constituents and their components the team were able to derive and optimise an ideal bioink composition for 3D bioprinting, which allowed for example enhanced tissue remodelling, and prevented significant fluid-uptake which would alter the geometric shape.

The researchers used the bioink to print 3D cylindrical blood vessels, consisting of living co-cultures of endothelial cells and vascular smooth muscle cells. These vessels were anatomically accurate, multicellular blood vessels which provided the opportunity to model vascular function and pathophysiology.

Using the bioprinted vessels the team were able to recapitulate thromboinflammatory responses which have only been observed in advanced in vitro preclinical models or in vivo.  Moreover, the cells in the vessels were stable and maintained a healthy phenotype for nearly one-month post-fabrication.

Conclusions and future applications

The team here have designed a blood vessel model that mimics its state of health and disease using a new class of nanoengineered bioinks, paving the way for cardiovascular drug advancements with better precision.

It is hoped that these 3D-bioprinted vessels will provide a potential new tool to understand vascular disease pathophysiology and will be a valuable new asset to assess therapeutics, toxins or other chemicals in preclinical trials. Such technology should advance and improve the translatability for use in vascular medicine.

From a regeneration perspective the ability to vascularise bioprinted organs and tissues will be a crucial milestone, and this technology is likely to help close this current gap.

Biofabrication is an emerging and fast-growing field of research that continues to develop ground breaking innovations.  A key area for its success will be the continued development of new biomaterials or bioinks for 3D printing, such as we have seen here and with other innovations such as self-healing gels that allow the bioprinting of complex biological tissue. Interestingly, self-healing materials such as elastomers are also being investigated to treat aneurysms, as they have tunable properties. 3D bioprinted models of such vessels may provide a good testbed for this type of technology.

The ultimate goal in the development of new bioink materials and the engineering of novel bioink formulations is to meet the ideal mechanical, rheological and biological properties found in nature, and it is hoped that the advancements made here by Gaharwar and Jain will be a step towards that goal and will expand the bioprinting tool box.

For more information please see the press release from Texas A&M University


Gold, K.A., Saha, B., Rajeeva Pandian, N.K., Walther, B.K., Palma, J.A., Jo, J., Cooke, J.P., Jain, A., and Gaharwar, A.K. 3D Bioprinted Multicellular Vascular Models. Advanced Healthcare Materials n/a, 2101141.