Matrix Metalloproteinase-Responsive Degradable Hydrogel-Based Bioprinted Multilayer Liver Models with Enhanced Hepatic Metabolic Functions for Drug Screening

Student’s name: Emma Berman Home Institution: University of California, Berkeley NNCI Site: SDNI @ UC San Diego REU Principal Investigator: Dr. Shaochen Chen – Department of Nanoengineering, UC San Diego REU Mentor: Ting-Yu Lu - Department of Nanoengineering, UC San Diego Abstract: 3D bioprinting has emerged as an intriguing approach for producing complex in vitro models. The goal of this project is to continue refining the digital light processing (DLP) printing method and enable the development of a 3D biomimetic liver model that recapitulates the native liver architecture. Specifically, we aim to incorporate stiffness tuning, degradability, and multi-layer printing into our liver model. We will assess the effects of non-degradable and degradable peptides in our hydrogel to control its degradability, which is crucial as cell spreading relies on matrix degradation via hydrolysis or proteolysis through cell-secreted matrix metalloproteinases (MMPs). Additionally, the hydrogel stiffness, ranging from 3-7 KPa, can be achieved by varying UV light intensity and exposure time, ensuring that the compressive moduli of the hydrogel matrices mimic those of reported liver tissue. We will present a 3D hydrogel-based co-culture model that embeds hiPSC-derived hepatocytes (hiPSC-HPCs), a major liver cell type, with human umbilical vein endothelial cells (HUVECs) as supporting cells. The endothelial extracellular matrix assists hepatocyte maturation, improving hepatic metabolic functions. This bioprinted, biodegradable, multi-layer liver model holds promise as a tool for early personalized drug screening and liver pathophysiology studies in vitro.