Bioprinted multilayered tissues for facial reconstruction
Facial reconstruction can benefit people whose features have been physically altered through accident, disease or violence. The procedure usually involves grafts of highly complex tissues, which are challenging to produce even for experts in engineering. One of the main problems is having enough blood supply. Most tissues in the human body rely on complex hierarchical vascular structures to nourish cells and remove waste. Transplants must have sufficient arteries, veins and capillaries to achieve the necessary exchange of gases and nutrients for the tissue to be accepted by the body and survive. “The challenges are to create multiscale vasculature totally integrating the tissue and feeding the tissue,” explains Shulamit Levenberg(opens in new window), a professor at the Technion – Israel Institute of Technology. “Without the vascularisation, the tissue will not get oxygen and nutrients, and the cells will die,” she adds. While facial elements including bone, skin and muscle have been successfully demonstrated, so far no composite soft tissues of facial layers have been created. In the VesselNet(opens in new window) project, which was funded by the European Research Council(opens in new window), Levenberg and her colleagues worked to further optimise a procedure which overcomes the challenges with facial composite tissue. The approach creates the vascular network in vitro before transplantation, allowing thicker tissues which are more likely to prove successful in transplantation.
Bioprinting composite tissue
Through the project, the team developed their technique which involves bioprinting the tissue in a way that before transplantation, it already has blood vessels. This includes large vessels to connect to arteries and veins, and a small capillary network that is connected to the large vessels. The goals of the project were to create an in vitro functional vascular network, engineer thick composite tissues and integrate these tissues to reconstruct a facial defect.
Developing a multilayered vascular system
The researchers successfully bioprinted multilayered soft tissue and bone tissue with multiscale vasculature, which works under continuous flow conditions. The results from the project were published in a series of peer-reviewed journals. The new multilayered vascular system uses various polymers shaped like blood vessels and arranged in a hierarchical way. Living tissues with capillaries were created within a human collagen bioink, and the capillaries get connected to vessel sprouts coming out from the large vessels. The structure of the system allows for continuous blood flow throughout the tissue. They were then able to use these tissues in animal models to repair large defects in bone, muscle and fat tissue. “We conducted experiments in small animals and large animals – as preclinical studies,” notes Levenberg, VesselNet project coordinator. The VesselNet approach could one day lead towards tailored, lab-grown tissues that could solve patient-specific problems.
Advancing reconstructive surgery
The thick composite tissues created through VesselNet could have major impacts on reconstructive surgery. The process and product will also improve our understanding of the mechanisms of tissue organisation itself. The team now hopes to develop the research further, and is seeking a grant to move towards clinical trials. The eventual goal is to repair large defects in tissues in humans following injury, trauma or surgeries removing cancerous tissue. “We are continuing to optimise the procedures including new printing methods and improved bioreactors for growing the tissue, and hope to move to clinical trials as soon as possible,” says Levenberg.
