Design and Development of a resorbable Bone Adhesive

描述（由申请人提供）：骨科小型骨和关节器械市场规模为18亿美元，增长率为8.9%。小骨和关节问题占骨科医生办公室就诊的51%和外科手术的24%。小骨的固定（即，桡骨远端骨折）由于难以使用螺钉和骨针而变得复杂，由于关节内错位和骨不连而导致的并发症发生率高达62%（Weber 1986）。骨粘合剂和骨水泥目前不用于这些手术中的许多手术中，因为它们是由粘合骨但不允许骨再生的化合物制成的。理想的骨修复粘合剂应促进而不是阻碍成骨细胞活性（Drobnic 2006），并应在骨自然愈合的时间范围内再吸收。该项目的长期目标是创造一种可吸收的小骨粘合剂，以满足手术对坚固的可吸收粘合剂的需求，以在内固定过程中粘合小骨碎片。拟议的I期研究项目的假设是，Cohera专有的生物相容性聚氨酯组织粘合剂可以设计成一种粘性配方，便于输送，具有适当的强度特征，可有效粘合小骨折。为了验证这一假设，将实现以下具体目标：1）优化未固化骨粘合剂的物理特性。简而言之，粘合剂的物理特性（例如粘度、固化时间和固化期间的放热温度）必须被设计成生产可以通过在手术室环境中注射以小体积递送同时满足既定性能要求的粘合剂。2)优化固化骨粘合剂的物理特性。将对根据具体目标1开发的候选制剂进行拉伸强度、杨氏模量和孔径检测。目标特征被定制为提供骨再生的环境，同时在愈合期间保持强度。在项目的第二阶段，将在体内测试骨粘合剂，以证明其在小骨折复位和固定方面的有效性。本研究项目将包括1）最终确定产品质量标准，2）在可接受的小骨修复动物模型中进行有效性试验，3）确定体内吸收率，以及4）评价缺损处的骨再生。积极的结果将导致在人类中进行研究，以向FDA提供数据，支持上市前批准（PMA）。.目前可用的骨粘合剂和粘固剂可以将骨表面粘合在一起，但不会随着时间的推移而再吸收并将伤口转变为自然愈合的骨。当骨水泥最终与骨分离时，这导致骨不连的发生率很高。该项目的长期目标是创造一种可吸收的小骨粘合剂，满足手术对骨固定方法的需求，允许骨再生，同时在愈合期间保持强度。

DESCRIPTION (provided by applicant): The orthopedic small bone and joint device market is 1.8 billion with an 8.9% growth. Small bone and joint problems account for 51% of office visits to orthopedic surgeons and 24% of surgical procedures. Fixation of small bones (i.e., distal radial fractures) is complicated by the difficulty in using screws and pins, and complication rates due to intra-articular misalignment and non-unions is as high as 62% (Weber 1986). Bone adhesives and cements are currently not used in many of these procedures because they are made from chemical compounds that bond bone but do not permit bone regrowth. An ideal adhesive for bone repair should promote rather than retard osteoblastic activity (Drobnic 2006), and should resorb in the timeframe of naturally healing bone. The long-term goal of this project is to create a resorbable small bone adhesive which would satisfy the surgical need for a strong, resorbable adhesive to adhere small bone fragments during internal fixation. The hypothesis of the proposed Phase I research project is that Cohera's proprietary biocompatible polyurethane tissue adhesive can be engineered into a viscous formulation for ease of delivery, with an appropriate strength profile that will be effective in bonding small bone fractures. To test this hypothesis, the following specific aims will be accomplished: 1) Optimize the physical characteristics of uncured bone adhesive. In brief, the physical characteristics of the adhesive (such as viscosity, cure time and exothermic temperature during cure) must be engineered to produce an adhesive that can be delivered in small volumes by injection in an operating room environment while meeting established performance requirements. 2) Optimize the physical characteristics of cured bone adhesive. The candidate formulations developed under Specific Aim 1 will be tested for tensile strength, Young's modulus, and pore diameter. The target characteristics are tailored to provide an environment for bone regrowth while maintaining strength during healing. During Phase II of the project, the bone adhesive will be tested in vivo to demonstrate efficacy in reduction and fixation of small bone fractures. This research project will include 1) finalizing the product specifications, 2) performing efficacy testing in an accepted animal model for small bone repair, 3) establishing resorption rates in vivo, and 4) evaluating bone regrowth in the defect. Positive outcomes will lead to studies in humans to provide data to the FDA in support of a Pre-market Approval (PMA). . Currently available bone adhesives and cements may bond bone surfaces together, but do not resorb over time and transition the wound to natural healed bone. This leads to a high rate of non-unions when cement eventually separates from the bone. The long-term goal of this project is to create a resorbable, small bone adhesive which would satisfy the surgical need for a method of bone fixation that permits bone regrowth while maintaining strength during healing.