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

这项小型企业创新研究(SBIR)第一阶段将专注于开发新型生物聚合物，这些聚合物是通过严格控制化学作用将多肽侧链共价连接到透明质酸(HA)主干聚合物链上而获得的。合成的材料可用于软组织增强、保护和年轻化。这项工作将依赖于实验和分子建模相结合的方法。在这种新的方法中，合成的多肽-HA聚合物是一种原位凝胶生物材料，在多肽侧链之间的疏水吸引的驱动下，在体内自组装成物理凝胶。分子模拟将指导多肽-羟基磷灰石聚合物的合成，形成具有所需机械和渗透性能的凝胶。凝胶中的物理交联物可以被注射针中的高剪切力可逆地分解，从而允许使用窄口径注射针来减轻患者的痛苦，并允许形成更坚硬、更有弹性的凝胶。这种创新的生物聚合物可能会超过目前使用的生物材料，因为它具有原位凝胶性，更好地控制和获得更广泛的凝胶特性，并且侧链可以用于携带具有生物功能的分子。该项目更广泛的影响/商业潜力将是一种能够满足理想的含有HA的真皮填充物的要求的新材料。这些要求包括无痛且易于注射到体内的材料，体内存活至少一年，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材料相比，这种材料将显著增强软组织增强的能力，并将有很大的需求。这种新型生物聚合物的性能可以调整为其他重要的和不断增长的生物医学应用，如关节炎关节的粘性补充和眼睛抗氧化保护。所提出的实验和分子建模相结合的方法还将提供对分子特征(组成和结构)与凝胶和由这些分子组成的溶液的宏观属性(机械和传输属性)之间的相互作用的独特的基本理解。所提出的分子模拟引导材料设计方法是一种最先进的技术，可以推广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.