Challenges and limitations
Despite the significant progress and many breakthroughs, bioprinting
technology still facing several serious challenges that delay
translating bioprinting structures to viable and functional tissues. The
greatest challenge is the ability to print an intra-organ vascular
hierarchical network, from arteries and veins down to capillaries,
without which tissues will not be able to survive. In vivo, a
vasculature network is required for tissues to grow beyond 100-200 µm
[Carmeliet and Jain, 200] as this is the diffusion limit of oxygen
[Malda et al 2004]. The fabrication of large tissue segments with a
high volumetric oxygen-consumption rate such as cardiac and liver
tissues would require adequate oxygen supply to prevent a shortage in
nutrient and tissue necrosis. Fabricating of blood capillaries is
currently restricted due to the current limitation of 3D printing
resolution, which is ~20 µm, while blood capillary can
be as small as 3 µm. Several promising solutions are being exploited to
create vascularized human tissue, for instance, by incorporating
angiogenic growth factors into bioinks to induce vasculature growth
after printing [Rouwkema et al 2008 and Kneser et al 2006]. Another
approach used a microfluidic device to induce vasculogenesis
[Zervantonakis, I.K. et al. 2012], however, the used hydrogels do
not support cell-cell interactions and affect phenotypic stability
[Ozbolat, 2015]. Owing to the complexity and small size of the
vasculature network, developing functional vasculature in a timely
manner to support the bioprinted tissue still not achievable to date.
Biomaterials play a primary role in 3d bioprinting for supporting the
structural and functional features of the printed tissue as well as
maintaining the structural integrity and biocompatibility during tissue
printing and maturation. Current available printable materials, however,
are not capable of fully mimicking the native ECM compositions to
support the cellular structure. Therefore, it is crucial to develop new
printable biomaterials that can be printed together with live cells and
possesses adequate mechanical properties for cell handling. Cell
sourcing is another great challenge as tissue printing requires a large
number of cells. Stem cell source would be the most promising choice as
bioprinting would be able to influence stem cell differentiation at
multiple stages of the process.