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

项目摘要/摘要 超过50%的45岁以上的美国成年人牙齿缺失。牙齿脱落后，牙槽骨部分 颌骨将会萎缩，这一过程称为残存的牙槽骨吸收。而种植体支持的牙冠有 成为护理的标准，市场调查表明，70%的患者必须接受牙槽骨隆起 提供足够的骨性结构以接受种植体植入的程序。骨移植的市场高度活跃。 碎片化，说明满足用户需求的理想素材不存在。大多数牙医留了下来 对现有的骨移植不满意，因为它们具有挑战性的处理性能和较差的可预测性。由于 缺乏结构完整性，它们通常需要额外的成本和步骤来放置辅助遏制装置 防止移植物迁移和纤维组织向内生长，从而阻碍骨再生。因此，次要的 30%的病例需要进行增强手术，以确保有足够的体积来放置种植体。 RevBio，Inc.开发了一种具有粘附性的高度多孔、可再生的骨移植生物材料，称为 Tetranite®粘附性牙科骨支架(TN-ADBS)。与目前可用的移植材料不同，TN-ADBS是 在应用过程中具有粘性，其独特的粘合性能使其能够保持形状，从而消除了对 辅助固定或遏制装置。TN-ADBS由O-磷酸-L-丝氨酸组成，其中部分 使其具有独特的骨粘附性，研究还发现，在其吸收和局部释放过程中 促进骨质疏松症，借出这款产品来生产更可预测和更有效的产品。 之前由美国国立卫生研究院-密歇根匹兹堡·怀斯再生医学资源中心提供的资金已经使用 为了：(A)开发TN-ADBS，(B)评估其在用户操作试验中的性能，(C)开发具有 (D)在该模型中进行初步疗效研究。根据FDA 反馈，TN-ADBS将作为设备主导的组合产品进行监管，其中OPLS是药物成分 促进骨再生。以下拟议的第二阶段拨款申请是根据FDA最近的规定设计的 针对以下两个具体目标的反馈：(1)评估TN-ADBS(OPLS)的局部/系统影响 和最大给药条件下新西兰白兔的药代动力学/药效学(PK/PD) 模型和(2)在一项关键的动物研究中证明TN-ADBS的安全性和有效性 TN-ADBS治疗颌骨局部或全身不良反应的临床应用 缺陷并不比对照组差，(Ii)在整个过程中表现出优越的脊高保持 与对照组相比，骨替代的发生率(p&lt；0.05)。 这些转译动物研究的结果是对外科医生验证的模拟使用试验的补充 和生物安全评估研究，将被用作提交调查设备豁免的基础 (IDE)与FDA合作启动人体研究。从长远来看，RevBio的使命是为外科医生提供一种新颖的 骨移植产品，简化手术并改善牙槽骨增高术的临床结果。

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.