The project aims delivery of drug-loaded hydrogels by a handheld device with a co-axial nozzle (like a common syringe). The project aims at design and optimization of the process. It involves measurement of the mechanical properties of hydrogels, studying cell behavior, design criteria for developing a handheld device, preparation techniques of hydrogels, generating experimental designs and printing different types of hydrogels with handheld devices.

Soft-tissue sarcoma (STS) is a group of aggressive tumors that grow in non-adherent conditions and are highly invasive and resistant to chemotherapy. The low effectiveness of chemotherapy demands proper pre-clinical STS models to evaluate anti-cancer drugs. However, there is a lack of in vitro models recapitulating tumor microenvironment (TME) within STS. Therefore, there is a critical need for better organotypic drug screening platforms to improve systematic therapies, reduce fabrication time, and identify predictive factors for response to chemotherapy drugs. The long-term goal of this research is to design and develop a bioprinted vascularized STS tumor spheroid-on-a-chip that will lead to possibilities for cost-effective drug discovery and personalized medicine. We have shown that multimaterial bioprinting has allowed us to tailor the mechanical properties of ECM mimicking hydrogel and positioning biologics on desired locations. This further will allow us to recapitulate the TME of soft tissue tumors and monitor cell behavior. Our published data and new preliminary data support the relevance of this model provide the basis for our hypothesis that the construction of an in vitro model can mimic the cellular composition and the ECM properties of tumor tissue for its in vivo counterparts. The immadiate goal of the proposed studies is to provide a proof-of-concept of bioprinted tumor-on-a-chip to meet the clinical need for rapid and inexpensive 3D in vitro soft tissue tumor models and drug screening platforms. Two specific aims are proposed 1) validating the biomimicry of our bioprinted tumor model and 2) measuring the specific cell markers in this organotypic tumor model. At the completion of the aims, we expect that this novel hydrogel microfluidic platform will provide a valuable tool for invasion with sarcoma spheroids used for drug discovery and development.

Current high-throughput screening (HTS) applies two-dimension (2D) standard well plate which requires complex handling equipment and automated system. Microfluidic cellular platform resolves the issues and as well provides reduced sample quantity and integration of cells. Conventional microfluidic device requires sequential integration of layer for complex structures making the fabrication process difficult and labor intensive. We intend to apply a patented (Patent Pending) multi-material 3D bioprinter to print hydrogel-based microfluidic platform to fabricate organ-on-a-chip and microfluidic device tool for high-throughput screening. The proposed work employs novel biofabrication method and hydrogel engineering to create a tool for developing effective therapeutics. The technology available allows rapid and continuous fabrication of microfluidic device which do not require post processing. The approach will allow us to fabricate organ specific microfluidic chip along with accessories such as electrodes within the device that may allow high-throughput detection of molecules. The hydrogel microfluidic chip a fluid-saturated solid network will ideally provide a proper cell-friendly environment and other biomimetic features. Additionally, these microfluidic platforms are anticipated to provide rapid analysis of numerous chemicals, biochemicals, or pharmacological tests in parallel in a real time setup.