Designing Bundlemer-Based Biomaterials for Therapeutic Applications

Hierarchically structured biomaterials are key components of the extracellular matrix, playing important roles in joint compression and lubrication. These biomaterials can be used for therapeutic applications, but their complex, hierarchical architectures have limited the development of scalable synthesis approaches using natural building blocks. “Bundlemers” are computationally designed biomaterial building blocks composed of four peptides assembled into a cylindrical, coiled-coil structure displaying reactive handles on the surface. Recently, our group has developed a platform for the scalable recombinant synthesis of bundlemers and has integrated non-natural and genetically encoded click chemistries to create bundlemer-based nanostructures. We have used these chemistries to modify bundlemers for the formation of higher-ordered structures, which then display pendant groups for conjugation of biofunctional moieties. To prepare these materials for use as injectable lubricants and therapeutic delivery vehicles, our current work is assessing their assembly kinetics and stability under relevant physiological, storage, and processing conditions (assessed with spectroscopy and microscopy techniques) and to enhance their stability under physiological conditions.