Collagen Mimetic Structures for Novel Biomaterials

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The area of collagen research has developed into an important focus for biomaterials technology. The search for robust and diverse collagen-based biomaterials has expanded into areas of drug delivery systems, ocular devices, wound healing therapies and artificial organs. In the Goodman laboratories, synthetic and biophysical strategies have been developed to design and investigate the properties of triple helical collagen mimetic structures as candidate biomaterials. %%%As an expansion of early work with n-isobutylglycine (Nleu) incorporated into the collagen trimeric building blocks Gly-Pro-Nleu and Gly-Nleu_Pro, fluorinated residues fluoroproline or N-(hexafluoro)isobutylglycine will now be incorporated into tripeptide building blocks. Their effects on triple-helical stability will be investigated by a series of biophysical measurements. The biophysical analysis includes temperature-dependent optical rotation measurements, circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy, molecular modeling, as well as studies of the thermodynamics of triple helix folding and hydrations. Biological profiles will be assessed by collaborators at Integra Life Sciences and the group of Andrea Tenner at the University of California, Irvine. In addition to novel building blocks, templates have been employed to enhance the stability of triple helices. Tris(hydroxymethyl)aminomethane (TRIS) has been successfully derivatized to create collagen mimetic arrays. The additional amine functional group provides a point of attachment to surfaces and other reactive molecules. The TRIS-terminated collagen structures will be utilized to create ditemplated molecules in which the collagen peptide chains are anchored at both the N- and C-termini. Ditemplated collagen units can be linked together in a chain as precursors for the formation of nanostructures (rod-like polymers). In line with template research, orthogonally protected scaffolds will be introduced in order to assemble heterotrimeric collagen structures to which unique biologically relevant peptide chains can be attached. This design will result in collagen mimetics that elicit specific biological responses to mimic natural collagen proteins such as collagen type I or the defense collagen protein C1q.