“Biomimetic Materials in Tissue Engineering”
Tissue engineers have had to select between natural (i.e., collagen) and synthetic (i.e., polyglycolic acid) polymer scaffolds. Each has its advantages and also its issues. Ideally, one would want specific cell-material interactions like those between cells and extracellular matrix (ECM) proteins while also having control over material properties and ease of processing that come with synthetic polymers. Therefore, biomimetic derivatives of polyethylene glycol (PEG) currently are being studied as scaffolds. PEG-based materials are hydrophilic, biocompatible, and intrinsically resistant to protein adsorption and cell adhesion. Thus, PEG provides a “blank slate”, devoid of biological interactions, upon which the desired biofunctionality can be built. Aqueous solutions of acrylated PEG can be rapidly photopolymerized in direct contact with cells, allowing encapsulation. In designing biofunctional derivatives of PEG, we have analyzed the processes active in the ECM and attempted to adapt these to this synthetic material platform. Several goals have been set in the design of these biofunctional hydrogel materials. For example, we hoped to design synthetic polymers that would be degraded by the cellular proteases. To accomplish this, we have incorporated peptide sequences into the polymer backbone that are substrates for targeted proteolytic enzymes. We have achieved biodegradation in response to the targeted protease, while the materials are stable in the absence of proteolytic enzymes or when exposed to non-targeted enzymes. Furthermore, cells are able to mediate degradation of these materials via their protease release during cell migration. It is also desirable to mediate cell adhesion via specifically targeted adhesion receptors. Since PEG is cell non-adhesive, cell adhesion to these hydrogels occurs only through specifically incorporated adhesion ligands. These materials are easily modified with acrylate-terminated peptides to add cell adhesion ligands to the hydrogel network. When modified with a common adhesion peptide, RGDS, cell adhesion and spreading occurred in a dose-dependent fashion, while cell adhesion and spreading did not occur on materials without a peptide or with the scrambled control peptide, RDGS. Additionally, since the base PEG hydrogels are cell non-adhesive, if cell-selective adhesion ligands are selected, it is possible to generate cell-selective materials. It is also possible to modify these hydrogel materials with biomolecules, such as growth factors, that provide cues to cells to optimize tissue formation by enhancing cell growth or altering gene expression. We have also developed advanced 3D micropatterning technologies that allow us to spatially control the immobilization of peptides and proteins for further control over cell microenvironments, behavior and organization.
When: 1/12/12 4:00 PM
Where: 1005 GBSF