Bone Adhesive Modeled After the Sandcastle Glue of P. Californica

描述（由申请人提供）：提出了一种仿生策略来开发一类用于骨科医学的新型粘合剂，特别是具有多骨碎片的关节骨折。这种粘合剂模仿了一种天然的水下粘合剂，这种粘合剂是由一种海洋管虫分泌的，可以将破碎的贝壳和沙粒粘合在一起。这种天然胶由几种具有简单重复序列的蛋白质和大量的二价金属离子组成。胶水蛋白的关键特征将被廉价、易于制造的合成聚合物复制。目标是：1)定量地将粘合剂的有效性（粘合强度、凝固/固化动力学、可交付性和可降解性的卷积）与配方变量和交付方法联系起来。这将通过微观和宏观尺度上的力学测试来完成。2)。通过对模拟共聚物的结构和化学性质进行微调，优化合成骨胶粘剂。这将通过控制聚合技术合成模拟共聚物来实现。3)。在体外和活体动物模型中明确确定模拟粘合剂和潜在分解产物的生物相容性。这将在多个相关细胞系的直接接触细胞培养实验中完成，并通过对动物黏附修复骨折的长期分析来完成。黏合剂降解和再吸收的速率将在体外和体内进行评估。

DESCRIPTION (provided by applicant): A biomimetic strategy is proposed to develop a new class of adhesives for orthopedic medicine, particularly joint fractures with multiple bone fragments. The adhesive is modeled after a natural underwater adhesive secreted by a marine tubeworm to glue together broken bits of seashells and sand grains. The natural glue is comprised of several proteins with simple repetitive sequences and significant quantities of divalent metal ions. The key features of the glue proteins will be copied with inexpensive, easy to manufacture synthetic polymers. The objectives are: 1.) To quantitatively correlate adhesive effectiveness (a convolution of bond strength, setting/curing kinetics, deliverability, and degradability) with formulation variables and delivery methods. This will be accomplished by mechanical testing on the micro and macro scales. 2.) To optimize the synthetic bone adhesive by fine tuning the structures and chemical properties of the mimetic copolymers. This will be accomplished by using controlled polymerization techniques to synthesize the mimetic copolymers. 3.) To definitively establish the biocompatibility of the mimetic adhesive and potential breakdown products both in vitro and in a living animal model. This will be accomplished in direct contact cell culture experiments with multiple relevant cell lines and by long term analysis of adhesive repaired bone fractures in the animal. Rates of adhesive degradation and resorption will be evaluated both in vitro and in vivo. PUBLIC HEALTH RELEVANCE: An injectable, low-viscosity bone adhesive would improve the clinical outcome for a broad population of orthopedic trauma patients by facilitating more accurate alignment of small bone fragments. Better alignment during bone healing decreases the risk of post- traumatic arthritis.