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制成的，用于将碎贝壳和沙粒粘在一起。天然胶由几种具有简单重复序列和大量二价金属离子的蛋白质组成。胶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.）定量关联粘合剂有效性（粘合强度、凝固/固化动力学、可输送性和降解性的卷积）与配方变量和输送方法。这将通过微观和宏观尺度上的机械测试来完成。2.）通过对仿生共聚物的结构和化学性质进行微调，优化合成骨粘合剂。这将通过使用受控聚合技术来合成模拟共聚物来实现。3.）第三章明确确定模拟粘合剂和潜在分解产物在体外和活体动物模型中的生物相容性。这将在使用多种相关细胞系的直接接触细胞培养实验中以及通过对动物中粘合剂修复的骨折进行长期分析来实现。将在体外和体内评价粘合剂降解和再吸收速率。 公共卫生相关性：一种可注射的低粘度骨粘合剂将通过促进小骨碎片的更准确对齐来改善广泛骨科创伤患者人群的临床结局。在骨愈合过程中更好的对线可以降低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.