Development of a Novel Bone Adhesive Scaffold to Accelerate Bone Regeneration and Improve Ridge Height Maintenance for the Treatment of Patients with Residual Ridge Resorption

开发新型骨粘合剂支架以加速骨再生并改善牙槽嵴高度维持以治疗残留牙槽嵴吸收的患者

• 批准号: 10603678
• 负责人: Rahul Jadia
• 金额: $ 126.54万
• 依托单位: REVBIO, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10603678
• 关键词: Acceleration; Address; Adhesives; Adult; Adverse effects; Age; Allografting; Alveolar; Animal Testing; Animals; Applications Grants; Area; Atrophic; Bilateral; Biocompatible Materials; Biological; Blood; Blood Chemical Analysis; Blood coagulation; Bone Regeneration; Bone Substitutes; Bone Transplantation; Breakthrough device; Canis familiaris; Clinical; Containment; Crowns; Cytoplasmic Granules; Data; Defect; Dental; Dental Implants; Dentists; Development; Devices; Drug Kinetics; Edentulous Mouth; Ensure; Evaluation Studies; Feedback; Femur; Funding; Growth; Height; Histologic; Human; Implant; Implantation procedure; In Vitro; Injections; Jaw; Maintenance; Mandible; Market Research; Marketing; Membrane; Michigan; Minerals; Mission; Modeling; New Zealand; Operative Surgical Procedures; Organ Transplantation; Oryctolagus cuniculus; Outcome; Outcome Measure; Particulate; Patients; Performance; Pharmaceutical Preparations; Pharmacodynamics; Phase; Phosphoserine; Plasma; Porosity; Procedures; Process; Property; Regenerative Medicine; Regulatory Pathway; Residual state; Resources; Safety; Saline; Serine; Structure; Surface; Surgeon; Time; Tissues; Tooth Loss; Tooth structure; United States National Institutes of Health; Width; X-Ray Computed Tomography; allogenic bone transplantation; biomechanical test; bone; bone preservation; bone scaffold; canine model; cohort; cost; dental adhesive; design; efficacy study; implantation; improved; meetings; migration; notch protein; novel; pharmacokinetics and pharmacodynamics; phase 2 study; preservation; prevent; regenerative; sample fixation; scaffold; sham surgery; soft tissue; standard of care; tetracalcium phosphate

PROJECT SUMMARY/ABSTRACT Over 50% of US adults over the age of 45 have missing teeth. Following tooth loss, the alveolar portion of the jaw will atrophy in a process known as residual ridge resorption. While dental implant-supported crowns have become the standard of care, market research indicates that 70% of patients must undergo a ridge augmentation procedure to provide adequate bony structure to accept implant placement. The market for bone grafts is highly fragmented, indicating that the ideal material meeting user needs does not exist. Most dentists remain dissatisfied with existing bone grafts due to their challenging handling properties and poor predictability. Due to the lack of structural integrity, they typically require extra costs and steps to place ancillary containment devices to prevent graft migration and fibrous tissue ingrowth that impedes bone regeneration. As a result, a secondary augmentation procedure is required in 30% of cases to ensure sufficient volume for implant placement. RevBio, Inc. has developed a highly porous, regenerative bone graft biomaterial with adhesive properties called Tetranite® Adhesive Dental Bone Scaffold (TN-ADBS). Unlike currently available graft materials, TN-ADBS is cohesive during application and its unique adhesive properties allow it to maintain form, eliminating the need for ancillary fixation or containment devices. TN-ADBS is comprised of O-Phospho-L-Serine (OPLS), which in part makes it uniquely adhesive to bone and studies have also found OPLS during its resorption and local release to be osteopromotive, lending this product to yield a more predictable and efficacious product. Prior funding from the NIH-Michigan Pittsburgh Wyss Regenerative Medicine Resource Center has been used to: (a) develop TN-ADBS, (b) evaluate its performance in user handling trials, (c) develop a canine model with a mandibular critical-sized defect, and (d) conduct preliminary efficacy studies in this model. Based on FDA feedback, TN-ADBS will be regulated as a device-led combination product, where OPLS is the drug constituent promoting bone regeneration. The following proposed Phase II grant application is designed per recent FDA feedback to address the following two Specific Aims: (1) to assess the local/systemic effects of TN-ADBS (OPLS) and pharmacokinetics/pharmacodynamics (PK/PD) under maximal use conditions in a New Zealand white rabbit model and (2) to demonstrate the safety and efficacy of TN-ADBS in a pivotal animal study for the intended clinical use to augment deficient jaw bone by (i) showing local or systemic adverse effects of TN-ADBS treated defects are non-inferior to controls and (ii) by showing superior ridge height maintenance throughout the course of bone substitution in comparison to controls (p<0.05). The results from these translational animal studies, complementary to surgeon-validated simulated use trials and biological safety evaluation studies, will be used as the basis for filing an Investigational Device Exemption (IDE) with the FDA to initiate human studies. Long-term, RevBio’s mission is to provide surgeons with a novel bone grafting product to simplify surgery and improve clinical outcomes for dental ridge augmentation.

项目摘要/摘要 超过50％的美国成年人45岁以上的牙齿。牙齿脱落后，大的一部分 下颌会在称为残留山脊分辨率的过程中萎缩。而牙科植入物支持的牙冠有 成为护理标准，市场研究表明，有70％的患者必须进行脊 提供足够的骨结构以接受植入物放置的程序。骨移植市场高度高 分散，表明不存在的理想材料满足用户需求。大多数牙医仍然存在 由于其挑战处理特性和可预测性差而对现有的骨移植物不满意。由于 缺乏结构完整性，他们通常需要额外的成本和步骤来放置辅助遏制设备 为了防止移植物迁移和阻碍骨再生的纤维组织侵蚀。结果，次要 在30％的病例中需要增强程序，以确保足够的植入物放置。 Revbio，Inc。开发了一种高度多孔的再生骨移植生物材料，其粘合特性称为 Tetranite®粘合剂牙科支架（TN-ADB）。与当前可用的移植物材料不同，TN-ADBS是 在应用过程中具有凝聚力及其独特的粘合特性允许其保持形式，从而消除了对 辅助固定设备。 TN-ADB由O-phospho-L-丝氨酸（OPL）组成，部分部分 使其对骨骼具有独特的粘合剂，研究也发现了OPL在分辨率和局部释放期间的OPLS。 成为骨剂，借用该产品以产生更可预测和有效的产品。 NIH-Michigan Pittsburgh Wyss再生医学资源中心的先前资金已被使用 到：（a）开发TN-ADB，（b）评估其在用户处理试验中的性能，（c）使用A开发犬类模型 下颌临界大小缺陷，（d）在此模型中进行初步有效性研究。基于FDA 反馈，TN-ADB将被调节为设备主导的组合产品，其中OPL是该药物构成的 促进骨再生。根据最近的FDA设计以下提议的II期赠款申请 反馈以解决以下两个具体目的：（1）评估TN-ADB的局部/系统效应（OPLS） 新西兰白兔子的最大使用条件下的药代动力学/药效学（PK/PD） 模型和（2）在关键动物研究中证明TN-ADB的安全性和效率 通过（i）显示已处理的TN-ADB的局部或全身性不良影响来增强颌骨缺乏的临床用途 缺陷不属于对照组，（ii）通过在整个课程中显示出较高的山脊高度维持 与对照组相比，骨骼取代（p <0.05）。 这些翻译的动物研究的结果，完成对外科医生验证的模拟使用试验的结果 和生物安全评估研究将被用作提出研究设备豁免的基础 （IDE）与FDA启动人类研究。长期，Revbio的使命是为外科医生提供小说 骨移植产物以简化手术并改善牙齿山脊增强的临床结果。