A Pilot Clinical Study for a Novel Bioresorbable Bone Adhesive to Evidence Improved Cranial Flap Fixation Based on Radiographic Imaging and Patient Reported Outcomes

Project Abstract In 2018 approximately 210,000 people in the U.S. underwent a craniotomy requiring cranial flap closure. The instruments used to cut into the skull leave a continuous gap (“kerf line”) between the bone flap and the surrounding skull. While cranial flap closure is relatively routine using plates and screws to fixate the flap, the industry has lacked any real innovation to improve the status quo in patient care. Clinical results are still plagued by many patients that spontaneously return with a loose or migrating plate, a devastating CSF leak or even infection that often requires surgical intervention. Not to mention, plates and screws cause artifacts that interfere with follow-up imaging (MRI or CT). Finally, plates and screws don't address the gaps left behind by the kerf line; therefore, bone healing does not fully complete across this space. As a result, patients often complain of pain and can feel the plates and screws through scalp and see depressions where the skin sinks—certainly this effects their self-esteem. While flap fixation can be augmented with existing bone cements to address some of these problems, they are not ubiquitously used because they lack desired handling properties and/or they significantly increase the cost of the cranial closure. RevBio’s bone adhesive biomaterial called Tetranite® (TN) could solve these issues. To accomplish this, the bone adhesive material is injected into the kerf line, forming a robust fixation bond between the bone flap and the surrounding skull and forming a water-tight seal upon setting. Overtime, the material serves as a scaffold as it is gradually resorbed and replaced with bone. Thus, the material serves many functions as a fixation device, a sealant, and a fusion device. Therefore, the goal for this project will be to advance the product from pre-clinical development into humans and be the first truly efficacious option for replacing hardware (e.g., plates/screws, clips) as a flap fixation methodology. The adhesive system has been fully developed, verified in a published pivotal animal study, and validated in user handling cadaver trials; therefore, the next stage in the project supported by the proposed grant application would accomplish the following Specific Aims: Aim 1: Produce and Test a Clinical-Grade Batch of TN for the Pilot Human Study, Aim 2A: Enroll Patients in Pilot Study and Demonstrate Feasibility of Intra-operatively Fixating Flaps with TN as a Stand-Alone Device, and Aim 2B: Patients Successfully Reach Primary and Secondary Endpoints at 6 and 12 Months Evidencing Safe Use and Probable Benefit to Advance to a Larger or Expanded Clinical Study. The proposed human pilot clinical study will demonstrate TN’s ability to fixate cranial flaps as a stand-alone and replacement to hardware fixation for the first time in humans and will substantiate those flaps restored using TN can withstand healing forces with desirable patient cometic outcomes while bone healing is occurring. This study will provide early assessment prior to initiating a larger clinical study and will compare performance to standard of care, i.e., plates and screws for cranial flap fixation.