Inducing Dental Implant Bone Formation to Treat Peri-implantitis

诱导牙种植体骨形成治疗种植体周围炎

• 批准号: 9408412
• 负责人: Malcolm L. Snead
• 金额: $ 22.5万
• 依托单位: INTEGRATED, LLC
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9408412
• 关键词: Address; Affinity; Alloys; Animal Experiments; Appointment; Binding; Biological; Biology; Biomimetics; Cell-Matrix Junction; Cells; Characteristics; Chemicals; Chronic Disease; Clinical; Coupling; Data; Defect; Dental; Dental Implants; Dentists; Elderly; Elements; Engineering; Ensure; Entrepreneurship; Failure; Fostering; Future; Goals; Health; Health Care Costs; Implant; Industry; Innovation Corps; Interdisciplinary Study; Interview; Life; Measurement; Measures; Metals; Microbial Biofilms; Modeling; Modification; Nanotechnology; Natural regeneration; Oryctolagus cuniculus; Osteogenesis; Pathway interactions; Patient Care; Patient risk; Patient-Focused Outcomes; Patients; Peptides; Performance; Phase; Process; Property; Proteins; Publishing; Reapplication; Recovery; Regenerative Medicine; Replacement Arthroplasty; Residual state; Risk; Safety; Services; Signal Transduction; Skeletal bone; Stem cells; Surface; System; Systemic disease; Techniques; Technology; Therapeutic; Time; Titanium; Tooth structure; Training Programs; WNT Signaling Pathway; Water; antimicrobial; base; bone; bone health; bone loss; clinical care; cohort; commercialization; cost; craniofacial; design; high risk; human stem cells; implant coating; improved; improved outcome; in vivo; innovation; insight; materials science; microorganism growth; nanobiotechnology; osteogenic; outcome prediction; patient population; peptidomimetics; peri-implantitis; skeletal; small molecule; stem cell biology; stem cell differentiation; success; surface coating

Project Summary Abstract The interdisciplinary research team at Integrated LLC has addressed a significant clinical need by developing a nanotech-bioactive water-based surface coating for titanium and titanium alloy based implants based on their advances in nanotechnology, stem cell biology. Our recently published data show that several of our peptides bind selectively and with high affinity to titanium and titanium alloys that are now used for dental implants and for correction of axial and craniofacial skeletal bone defects and joint replacements. Using this implant surface binding peptide as an anchor in combination with another small protein molecule enables us to introduce a bioactive function. Here we chose as a proof of concept, a small molecule we discovered that transiently activates the Wnt pathway for osteogenesis. Other bioactive functions such as an anti-microbial to control biofilms is also envisioned. This technology is water-based and the bifunctional small molecule approach serves to control the presentation of the biologically active peptides or protein at the implant interface to ensure cellular bioactivity. This promising nanotech-bioactive coating technology is designed to improve outcomes for all patients, including those challenged with advanced age or systemic diseases that are not now candidates for implants because of their high risk status. The coating also builds on the success of titanium surfaces to activate Wnt signals. Building upon the team`s accumulated expertise in bio- nanotechnology, materials science, stem cell biology, osteogenesis, and craniofacial biology, we developed peptides that mimic the characteristics of a biological surface on titanium or titanium alloy implantable material surfaces, thereby producing a biomimetic hard-soft interface that promotes cell attachment, while simultaneously directing the differentiation of the attached cells to osteogenic lineages in a single step. Our premise is that through the design of a self-organized bioactive interface on the implant surface we can further activate the canonical Wnt signaling pathway to direct the differentiation of stem cells to osteogenic lineages and improve osteointegration. Additionally, the coating can be used to re-treat previously placed implants that are failing due to bone loss from peri-implantitis to extend their useful life. Aim 1. Characterize the stability and temporal capacity of our biomimetic interface to retain Wnt signaling in vivo using a rabbit model well known to the implant industry.

项目摘要摘要 Integrated LLC的跨学科研究团队通过开发解决了巨大的临床需求 基于 它们在纳米技术，干细胞生物学方面的进步。我们最近发布的数据表明，我们的几个 肽有选择性地结合，对钛和钛合金具有高亲和力，这些肽现在用于牙齿 植入物以及纠正轴向和颅面骨骼骨缺损和关节置换。使用此 植入物表面结合肽作为锚固剂与另一个小蛋白质分子结合使用，使我们能够 引入生物活性功能。在这里，我们选择作为概念证明，我们发现的一个小分子 瞬时激活Wnt途径以进行成骨。其他生物活性功能，例如抗微生物 还设想了控制生物膜。这项技术是水基的，双功能小分子 方法可以控制植入物的生物活性肽或蛋白质的呈现 界面以确保细胞生物活性。这种有希望的纳米技术生物活性涂料技术旨在 改善所有患者的预后，包括受到高级年龄或全身性疾病的患者的结果 由于其高风险状况，现在不是植入物的候选人。涂层也建立在 钛表面激活Wnt信号。基于团队在Bio-的积累专业知识的基础上 纳米技术，材料科学，干细胞生物学，成骨和颅面生物学，我们发展了 模仿钛或钛合金植入材料的生物表面特征的肽 表面，从而产生一个仿生的硬柔软界面，可促进细胞附着，而 同时将附着的细胞的分化在一个步骤中指向成骨谱系。我们的 前提是，通过在植入物表面上的自组织生物活性界面的设计，我们可以进一步 激活规范的Wnt信号通路，以将干细胞的分化转移到成骨谱系 并改善稳定性。此外，涂层可用于重新治疗以前放置的植入物 由于植入物炎的骨质流失而导致其使用寿命。目标1。表征稳定性和 我们的仿生界面的时间容量使用众所周知的兔模型保留体内Wnt信号传导 植入工业。