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，以开发一种用于骨科医学的新型粘合剂，特别是具有多个骨碎片的关节骨折。这种粘合剂是模仿海洋管虫分泌的一种天然水下粘合剂，将贝壳碎片和沙粒粘合在一起。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。胶蛋白的主要特征将被复制到廉价、易于制造的合成聚合物中。目标是：1.)将粘接效果(粘结强度、固化/固化动力学、交付能力和降解性的卷积)与配方变量和交付方法定量关联。这将通过在微观和宏观尺度上进行机械测试来实现。2.)通过微调模拟共聚物的结构和化学性质，优化合成骨粘剂。这将通过使用受控聚合技术来合成模拟共聚物来实现。3.)在体外和活体动物模型中，确定模拟粘附剂和潜在的分解产物的生物相容性。这将在与多个相关细胞系的直接接触细胞培养实验中完成，并通过对粘连修复的动物骨折进行长期分析来完成。粘附剂的降解和吸收的速度将在体外和体内进行评估。 公共卫生相关性：一种可注射、低粘度的骨粘合剂将通过促进更准确的小骨碎片对齐，改善广大骨科创伤患者的临床结果。在骨骼愈合过程中，更好的对准降低了创伤后关节炎的风险。

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.