A Novel Opioid-Free Targeted Pain Control Method for Acute Post-Operative Localized Pain Related to Oral Surgical Procedures

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Project Summary/Abstract Drug addiction and overdose are a major problem in the US, accounting for 70,237 deaths in 2017. Over 60% of drug overdose deaths involved misuse of prescription or illicit opioids, and 30% of opioid prescriptions are written following oral surgical or dental procedures. Approximately 10 million wisdom teeth are removed annually. A statistically significant 6.8% absolute risk increase in persistent opioid use and a 5.4% increase in the subsequent diagnosis of opioid abuse follows a single course of opiates following wisdom tooth extraction. Therefore, there is a compelling need to develop a front line, non-opioid-based acute pain management strategy for outpatient oral surgical procedures. LaunchPad Medical has developed Tetranite® (TN), a novel bone regenerative mineral-organic self-setting adhesive biomaterial. TN has been extensively studied in vivo in a canine jaw model and shown to be effective and well-tolerated. Additionally, preliminary in vitro studies have shown that medication can be incorporated into TN formulations and released over time, and it is well established that the release profile of a target drug can be tailored to time-dose curve using conventional time release technology such as passive diffusion. Administering locally-acting analgesics (e.g., naproxen), local anesthetics (e.g., bupivacaine) and/or gabapentinoids (e.g., pregabalin) passively released over the 5-day window when pain relief is most needed, is a strong and innovative strategy for limiting acute postoperative pain following wisdom tooth removal, while employing TN as a filler/sealant will allow for simultaneous occlusion of environmental irritants to the bone wound, thus preventing osteitis and allowing bone regeneration. In this Phase I project, we will demonstrate that drug-loaded TN can be a novel route to providing localized and time release pain medication following wisdom tooth extraction by determining the release profile of various pain medications from TN at different concentrations (Aim I), verifying the consistency of TN handling and exotherm in compounded formulations (Aim II), and verifying the biocompatibility of TN-drug formulation in vitro using human osteoblasts (Aim III). The ability to release pain therapeutics in a controlled fashion and directly at the site of injury offers improved pain control following oral surgical procedures without exposing the patient to opioids. In addition, this novel approach to pain management can be extended to more invasive orthopedic procedures such as joint replacement, spinal fusions or reconstructive trauma surgery. In Phase II we will conduct an in vivo study to assess efficacy of medicated TN to address post-operative pain following wisdom tooth odontectomy, optimize incorporation and release of medications in TN formulations, develop cGMP manufacturing process for the compounded product, and ultimately conduct clinical trials for bone void filler using medicated TN.