Challenges

Although the idea of building tissues and organs has long been envisioned, bioprinting is still a very new process. While the concept seems possible, its full potential has yet to be fully demonstrated. Despite much progress and a number of breakthroughs in this area, researchers have met many challenges. There are many design considerations, only a few are discussed below, to factor in the design and development of the process and bioprinting devices. Utilizing emerging technologies and advances (in all fields) and optimizing the current state-of-the-art process and tools will progress bioprinting further.

As already noted, an organ blueprint should not only provide an accurate representation of the desired tissue, but also factor in dynamic events such as tissue fusion, compaction and retraction and constant remodeling. However, designing a bioprint to consider post-processing fusion, remodeling, retraction and compaction after printing and solidification is a challenging task. To resolve this, one modification to the blueprint would require it to be larger and slightly shaped differently from the final desired tissue structure. The CAD drawing may also need to include coefficients that estimate these remodeling factors. Furthermore, to accurately capture and simulate dynamic tissue self-assembly and post-processing remodeling, computer simulations must be improved in order to be utilized in the organ printing process. However, novel software and blueprints may lead to more effective solutions.

There are also challenges to improving and optimizing the biofabrication process. Currently, biopaper is characterized as a bioprocessible biomimetic hydrogel that have been generally used as matrices or scaffolds for bioprinting. Ideally, biopaper must be capable of rapid solidification, be dispensible, functional with growth factors, non-toxic to enable high cell viability (biocompatible), stimuli-sensitive and cross-linkable, capable of tissue fusion, hydrophilic and able to maintain shape, biodegradable and low cost. Thus far, naturally derived hydrogels such as collagen have been used. Improvements in the biomaterials used as bioinks and biopaper are needed before real clinical application potential can be realized. It is necessary to optimize bioinks such as their deformation and fluidic (rheological) and surface properties.

While studies have demonstrated the potential of dispensing and depositing single cells, more difficulty lies in developing a standardized scalable fabrication method for the robotic delivery of cell aggregates or tissue spheroids. Following that, biocartridge designs must also be modified. There are important challenges in designing and fabricating a bioprinter that is biologically "friendly" with rapid prototyping capabilities. Possible solutions that may address and answer these challenges include the use of temporary, removable porous needles. These type of needles may provide temporary mechanical support and perfusion of the printed scaffold essential in the post-processing step. In addition, enhancing the ability to develop vascular systems, these needles may enable the automatic printing of vascular-like tubular structures from self-assembling cell aggregates or fused vascular spheroids.

It is not enough to be able to print an organ. It is necessary for the printed tissue construct to undergo post-conditioning to acquire properties similar to native tissue. Bioreactors used in classical tissue engineering research differ from the ideal bioreactor for bioprinting. The bioreactor must meet a number of challenges including continuous perfusion, enabling accelerated tissue maturation and functionality for intravascular perfusion initiation, maintaining cell viability and vascularization, and dynamic biomechanical conditioning. Ideally, all components in the biofabrication process should be smoothly integrated to allow for easy transitioning of the tissue construct from the printed state (in a wet environment) to the post-conditioning state (transfer to bioreactor). The use of modern software and manufacutring device and process improvements with the aid of robotic biofabrication equipment may lead to revolutionary changes in this area.
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