SBIR Phase I: Peptide-modified Hyaluronic Acid Biopolymers for Soft Tissue Augmentation, Protection and Rejuvenation

This Small Business Innovation Research (SBIR) Phase I will focus on development of novel biopolymers obtained by covalently attaching peptide side chains to hyaluronic acid (HA) backbone polymer chains through carefully controlled chemistry. The resulting material can be used for soft tissue augmentation, protection, and rejuvenation. The work will rely on a combined experimental and molecular modeling approach. In this novel approach, the synthesized polypeptide-HA polymer is an in-situ gelling biomaterial that self-assembles into a physical gel inside the body driven by hydrophobic attractions between the peptide side chains. Molecular modeling will guide the synthesis of polypeptide-HA polymers that form gels with desired mechanical and osmotic properties. The physical crosslinks in the gel can be reversibly broken down by high shear forces in the injection needle, allowing use of a narrow gauge injection needle that reduces patient pain and allows for formation of stiffer, more resilient gels. The innovative biopolymer is likely to outperform currently used biomaterials because of in-situ gelling, better control of and accessibility to a wider range of gel properties and the side chains can be used to carry molecules with biological functionality. The broader impact/commercial potential of this project will be a new material that can meet requirements for an ideal HA-containing dermal filler. These requirements include a material that is pain-free and easy-to-inject into the body, in vivo survivability for at least one year, absence of immunogenic or allergic reactions, enhanced water retention, tunable mechanical properties, attachment of functional molecules, and low cost. Such a material will significantly enhance capabilities for soft tissue augmentation over existing HA-based materials and will be in large demand. The properties of the novel biopolymer can be tuned for other important and growing biomedical applications such as viscosupplementation for arthritic joints and ocular antioxidant protection. The proposed combined experimental and molecular modeling approach will also provide a unique fundamental understanding of the interplay between molecular characteristics (composition and architecture) and macroscopic properties (mechanical and transport properties) of gels and solutions comprised of these molecules. The proposed molecular simulation guided material design approach is a state-of-the-art technology that can be extended for development of other complex materials.