Creating and Analyzing Artificial Tissues

Organ and tissue transplantation faces many obstacles. Not the least of these is the unwanted immunogenicity of the graft, which requires lifelong immunosuppressive therapy. This has side effects that can range from unpleasant to severe. To address this and other obstacles, one promising approach is decellularization–recellularization, in which biochemical approaches are used to tease cells out of tissues or organs, leaving behind the biological scaffold that is subsequently be repopulated with the recipient’s own cells.  This significantly reduces the need for immunosuppression and, while the technology is in its infancy, it is very promising. However, it shares a major stumbling block with regular transplantation, namely dependency on a donor pool that is heavily oversubscribed.

So, is there a good alternative strategy that bypasses the donor issue? I believe that synthetic tissue could fit the bill. It is another young but fast-developing concept that has already demonstrated significant clinical potential. Biocompatible materials can be formed into porous or fibrous scaffolds; these architectures provide a substrate for cell seeding, much like organs in the decellularization/
recellularization process.

One goal of this approach is to patch damaged and/or ageing tissues or organs. In early attempts, the biomaterials used prevented cell infiltration throughout the entire scaffold and the cells only grew in
two dimensions.

To solve this problem, I have been applying bio-electrospraying and cell electrospinning. These techniques combine living cells, essential biomolecules, and a viscous biopolymer to form true three-dimensional structures that mimic native tissues and organs. By making use of a high voltage across electrodes, bio-electrospraying draws a jet that undergoes breakup to form cell-laden droplets for pinpoint placement in three-dimensions; cell electrospinning creates a continuous cell-containing fiber that forms a scaffold. Both approaches mimic three-dimensional native tissues, allowing cells full access to nutrients.

We have performed in depth in vitro and in vivo studies of bio-electrospraying and cell electrospinning in mouse and rat models, and we are currently engaged in challenge trials in pigs and sheep. Many fully functional tissue types, such as skin, muscle, cardiac, and brain, have been generated in sheets or vessels. These contain multiple cell types and a whole host of biomolecules to enhance selected features, such as vascularization and wound healing.

Although the original focus of our bioplatform research was the construction of three-dimensional synthetic tissues for repair, replacement, or rejuvenation, it offers great potential in an analytical or diagnostic setting. In fact, we are investigating the potential of cell electrospinning/bio-electrospraying bioplatforms at a smaller scale for high-throughput applications. Tissues of a specific type – for example, cancer or otherwise disease-specific tissue – is fabricated at the millimeter scale in a 96-well format, enabling rapid screening of targeted small molecule therapies against experimental, clinical, or genetic criteria, for example, age-related and/or hereditary diseases.

The progression from in-vitro models (functional assays) to in-vivo systems that more closely mimic disease is an exciting one and will provide fundamental analytical insight into many aspects and therapeutic targets that were previously beyond study. The analysis of three-dimensional tissues in massively parallel studies will provide insights on disease progression and translational implications (for example, wound healing). And by using genome sequencing and subsequently identified at-risk organ biopsies, patient-specific tissue arrays could be created for drug screening or even discovery with a view towards personalized medicine.