Tuesday, June 11, 2019
Cell-derived (CDM) matrix scaffolds provide a 3-dimensional (3D) matrix material that recapitulates a native, human extracellular matrix (ECM) microenvironment. CDMs are a heterogeneous source of ECM proteins with a composition dependent on the cell source and its phenotype. CDMs have several applications, such as for development of cell culture substrates to study stromal cell propagation and differentiation, cell or drug delivery vehicles, and regenerative biomaterials. Although CDMs are versatile and exhibit advantageous structure and activity, their use has been hindered due to the prolonged culture time required for ECM deposition and maturation in vitro. Macromolecular crowding (MMC) has been shown to promote ECM deposition and organization by limiting the diffusion of ECM precursor proteins and allowing the accumulation of matrix at the cell layer. A commonly used crowder that has been shown to increase ECM deposition in vitro is Ficoll, and was used in this study as a positive control. Hyaluronic acid (HA), a natural crowding macromolecule expressed at high levels during fetal development, has been shown to play a role in ECM production, organization, and assembly in vivo. However, HA has not been reported as a crowder molecule in cell-based systems for driving ECM deposition and assembly, or for the development of CDM scaffolds. Thus, the focus of this study was to evaluate the effect of HA as a macromolecule for promoting in vitro deposition of ECM proteins important for tissue regeneration and angiogenesis, as well as for development of CDMs to support exogenous delivery of antimicrobial peptides.
Marsha Rolle, PhD, Associate Professor, Biomedical Engineering, WPI (Thesis Advisor)
Jeannine Coburn, PhD, Assistant Professor, Biomedical Engineering, WPI (Chair)
Kristen Billiar, PhD, Professor, Biomedical Engineering, WPI
Tanja Dominko, PhD, Associate Professor, Biology and Biotechnology, WPI
Michael Zimber, PhD, Director of Applied Research, Histogen INC
Department of Biomedical Enginnering