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.