Friday, April 29, 2011 – 1:15pm
Reiss 261A
Silviya Zustiak

While great strides have been made in developing new biomaterials, tissue engineering efforts focused on nerve repair have been limited by a rudimentary understanding of how neurons interact with their three-dimensional (3D) environment. The objective of this work was to create degradable 3D hydrogel scaffolds with defined biological and mechanical properties, as well as tunable degradability that would allow the study of dynamic neuronal-matrix interactions.

The development of in vitro models that enable elucidation of the mechanisms of system performance is a recently emerging goal of tissue engineering. The design of 3D scaffolds in particular, is motivated by the need to develop model systems that better mimic native tissue as compared to conventional two-dimensional (2D) cell culture substrates. An ideal scaffold is degradable, porous, biocompatible, with mechanical properties to match those of the tissues of interest and with a suitable surface chemistry for cell attachment, proliferation, and differentiation. Although naturally derived materials are more versatile in providing complex biological cues, synthetic polymers are preferable for the design of in vitro models as they provide a wider range of properties, controllable degradation rates, and easier processing. Most importantly, their mechanical properties can be decoupled from their biological properties, a critical issue in interpreting cell responses.

Thus, we report the synthesis and characterization of novel hydrolytically degradable poly(ethylene glycol) (PEG) hydrogels composed of PEG-vinyl sulfone (PEG-VS) cross-linked with PEG-diester-dithiol. We present results from biophysical structure-function studies with a focus on: a) characterization of hydrogel porosity and stiffness with hydrogel degradation (degradation spanned from hours to days accompanied by a 20-fold change in hydrogel physical properties), b) characterization of solute diffusion in the hydrogels via bulk diffusion and Fluorescence Correlation Spectroscopy methods, c) addition of adhesive ligands to the hydrogel scaffolds to promote neuronal outgrowth (in some cases addition of ligands also lead to change in the hydrogel physical properteis), and d) investigation of neuronal response to these scaffolds by varying hydrogel properties (90% or higher viability was achieved with all hydrogel types).

This work unveils new fundamental quantitative relationships between scaffold structure and neuronal function and provides a foundation for ongoing work focusing on the design of scaffolds for directed neuronal response and advanced model systems for in vitro neurobiological studies.

Host: Daniel Blair