UC San Diego

Tissue engineering encompasses a wide variety of goals, including but not limited to the repair, improvement, or replacement of whole tissues or organs, as well as in vitro investigations of native physiology and functionality. The incorporation of three-dimensional (3D) printing as a biomanufacturing technique in recent years has greatly contributed to the field of tissue engineering, granting enhanced capability in fabricating bioartificial constructs that can be used across a myriad of applications, including inducing endogenous regeneration, recapitulating existing pathophysiology, or investigating drug-tissue interactions. Among the varieties of 3D printing paradigms, light-based 3D bioprinting techniques, such as Digital Light Processing (DLP)-based modalities, have significantly advanced fabrication speed, resolution, and biomanufacturing capability by enabling fabrication options that would be challenging to implement using more traditional extrusion-based techniques. In this work, we investigate the use of DLP-based 3D printing as both a supportive and direct manufacturing platform in the context of tissue engineering and microphysiological systems.

First, a review of extrusion and light-based 3D printing approaches in the manufacturing of functional biomedical microdevices is addressed. The differences between various 3D printing paradigms, their advantages and disadvantages, and several showcases of their capabilities are discussed. Next, the utilization of DLP 3D printing as a dual-purpose microfluidic and in situ tissue scaffold fabrication technique for the purpose of dynamic cell culture microenvironment control is discussed. A passive micromixer was developed and evaluated for its mixing efficiency, and DLP 3D printing was used to fabricate tissue scaffolds inside the enclosed microfluidic device. Next, in situ DLP 3D printing into well-plates in the context of high throughput pharmaceutical compound screening is investigated. 3D bioprinted liver-based tissue scaffolds were fabricated at high throughput rates. The speed and dimensional accuracy of printing, cell viability, functional chemotherapeutic assays, and multi-cellular 3D bioprinting were investigated. Finally, a combination of DLP 3D printing and microfluidics is utilized in the development of a novel Placenta-on-a-Chip microphysiological system. A ‘hybrid’ open/closed 3D microfluidic device was fabricated, utilizing multiple primary human cell sources to generate a tri-coculture in vitro model. Tri-coculture viability, barrier integrity, and transfer rates of solutes-of-interest were investigated. In summary, these explorations of Digital Light Processing (DLP)-based 3D printing as a biomanufacturing platform for the creation of microphysiological systems provide significant scientific and translational advancement in the fields of 3D cell culture, microphysiological systems, and pharmaceutical drug discovery.