Design and Development of a resorbable Bone Adhesive

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.