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

该小型企业创新研究（SBIR）第一阶段将专注于开发新型生物聚合物，该生物聚合物通过仔细控制的化学反应将肽侧链共价连接到透明质酸（HA）主链聚合物链上。 所得材料可用于软组织增强、保护和再生。 这项工作将依赖于实验和分子建模相结合的方法。 在这种新方法中，合成的多肽-HA聚合物是一种原位凝胶化生物材料，其在肽侧链之间的疏水吸引力的驱动下在体内自组装成物理凝胶。分子建模将指导多肽-HA聚合物的合成，所述聚合物形成具有所需机械和渗透性质的凝胶。凝胶中的物理交联可以通过注射针中的高剪切力可逆地分解，从而允许使用窄规格注射针，其减少患者疼痛并允许形成更硬、更有弹性的凝胶。这种创新的生物聚合物可能优于目前使用的生物材料，因为它具有原位胶凝、更好地控制和获得更广泛的凝胶特性，并且侧链可用于携带具有生物功能的分子。 该项目更广泛的影响/商业潜力将是一种新材料，可以满足理想的含HA皮肤填充物的要求。 这些要求包括无痛且易于注射到体内的材料、至少一年的体内存活性、没有免疫原性或过敏反应、增强的保水性、可调的机械性能、功能分子的附着以及低成本。与现有的HA基材料相比，这种材料将显着增强软组织增强的能力，并且需求量很大。 这种新型生物聚合物的特性可以被调整用于其他重要的和不断增长的生物医学应用，如关节炎关节的粘弹性补充和眼部抗氧化保护。所提出的结合实验和分子建模的方法也将提供一个独特的基本理解的分子特性（组成和架构）和宏观性质（机械和运输性能）的凝胶和解决方案组成的这些分子之间的相互作用。所提出的分子模拟引导的材料设计方法是一种最先进的技术，可以扩展到其他复杂材料的开发。

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.