2, Radiological Sciences, Uniformed Services University of Health Sciences, Bethesda, Maryland, United States
Despite the expanding use of 3D bioprinting and a growing number of commercially available 3D bioprinters, there has been limited effort to develop a universal cell and tissue culture platform that enables the plethora of new approaches made possible with 3D printing. Traditional cell culture formats like the well-plate and transwell insert are routinely employed as the receiving container for bioprinted tissues but they present challenges when it comes to perfusion, harvesting, transfer of the printed tissues and accessibly to other tools and instruments. The ability to fabricate tissues in “freeform” is one of the advantages of 3D bioprinting, yet tissues remain confined to the receiving substrate, or lack a method of registration with other devices. The U.S. Naval Research Laboratory has developed “framed biopapers” as a novel and potentially universal format for 3D printing, handling, stacking and transferring tissues with registration between layers and devices.
In its most basic application, a single framed biopaper may be used as the base substrate for freeform 3D bioprinting. In this way, the framed biopaper provides a method to handle the 3D printed construct and easily releases the tissue construct through dematerialization of the biodegradable biopaper. Additionally, the frames of the biopaper provide for a registration mechanism for transfer from one bioprinting or biofabrication tool to another, as well as to bioreactors and analytical instruments, such as a microscope or plate reader. Furthermore, framed biopapers enable an asynchronous layer-by-layer fabrication approach whereby sheet-like layers are printed to individual biopapers and allowed to mature independently before stacking. This allows for specific application of growth factors or stimulus and the construction of complex heterotypic tissues, especially those with a laminar architecture. Finally, we envision that the frame of the biopaper may even be used as a surgical guide for implantation of tissue constructs, precision engineered to fit into a defect/void with alignment of implant and native vasculature and other tissue architecture for more rapid suture, anastomosis and integration into the body.