Fidelity of Biodegradable Patches Fabricated by a Custom-developed low-cost 3D Bioprinter

There is high demand in the medical field for biodegradable patches for a variety of applications such as wound healing. To keep the cost of the patches low, they would need to be fabricated using a high throughput, rapid method. Three-dimensional (3D) bioprinting is a promising technology that would make it possible to fabricate custom patches in such a high throughput, low-cost manner. Current commercial bioprinting systems tradeoff between resolution and throughput, and are inaccessible to researchers due to their high costs, ranging from $10k to over $200k. Patch fidelity to the original design is an important aspect of the manufacturing process, ultimately influencing their functionality. A patch must be fabricated as close to its Computer-Aided-Design (CAD) model as possible, maintain its form for a certain period of time on the target tissue, then biodegrade. Deformation during the manufacturing, or biodegradation processes can limit the patch’s performance. Fidelity on a 3D bioprinted biodegradable patch is analyzed in three dimensions: shape, mechanical and chemical fidelity. The former is concerned about preserving the shape of the printed filament and the accuracy of the patch structure. Mechanical fidelity is measures how well the patch preserves its structure under mechanical loads, such as those found once implanted in a body. Lastly, chemical fidelity is the ability of a patch to preserve its properties when exposed to chemicals such as body fluids and blood, such as during the degradation process. Assessing the fidelity and quantitatively characterization of a patch’s properties are crucial for material development. This thesis focuses on developing a custom-made, low-cost and high-throughput hybrid printer for manufacturing 3D biodegradable patches, and providing thorough fidelity analysis of said patches through controlled experiments mimicking native tissue conditions. First, a low-cost hybrid bioprinter with an inkjet and an extrusion print head was developed and implemented with the heads capable of printing gelatin methacryloyl and alginate respectively. The geometric accuracy of the printer was characterized. The printing and crosslinking parameters were then optimized to maximize the cell viability. Next, two novel shape fidelity experimental analysis techniques were developed, along with a mathematical model in supportive of one of the methods. These techniques are readily accessible and replicable, enabling rapid optimization of custom bioink formulations, accelerating the development processes. Finally, 3D bioprinted biodegradable patches were analyzed for shape, mechanical and chemical fidelity to improve their functionality. These patches are bioprinted using two custom hydrogels made of hybridized alginate and cellulose nanocrystal (CNC), or alginate and TEMPO oxidized cellulose nanofibril (TCNF). Both formulations were ionically crosslinkable using calcium chloride. These hydrogels were rheologically characterized, and printing parameters using an extrusion printing head were tuned to optimize shape fidelity. Mechanical fidelity of patches was assessed by cycling loading experiments, emulating the stresses caused by human tissue motion. 3D bioprinted patches were exposed to a solution mimicking body fluid to characterize biodegradability of the patches. Biocompatibility of the hydrogels were tested by cell viability analysis.