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 Integrated LLC的跨学科研究团队通过开发 一种用于钛和钛合金基植入物的纳米技术生物活性水基表面涂层， 他们在纳米技术干细胞生物学方面的进展我们最近公布的数据显示， 肽选择性地并以高亲和性结合现在用于牙科的钛和钛合金 植入物和用于轴向和颅面骨骼缺损的矫正和关节置换。使用此 作为锚与另一种小蛋白质分子结合植入表面结合肽使我们能够 引入生物活性功能。在这里，我们选择了一个小分子作为概念验证，我们发现， 瞬时激活Wnt通路用于骨生成。其他生物活性功能，如抗微生物， 还设想了对照生物膜。该技术是水基双功能小分子 该方法用于控制生物活性肽或蛋白质在植入物处的呈递 界面以确保细胞生物活性。这种有前途的纳米生物活性涂层技术旨在 改善所有患者的结局，包括那些患有高龄或全身性疾病的患者， 由于其高风险状态，现在不是植入物的候选者。涂层还建立在成功的基础上， 钛表面激活Wnt信号。基于团队在生物技术领域积累的专业知识， 纳米技术、材料科学、干细胞生物学、骨生成和颅面生物学，我们开发了 模拟钛或钛合金可植入材料上的生物表面特征的肽 表面，从而产生促进细胞附着的仿生软硬界面， 同时在单个步骤中引导附着的细胞分化成成骨谱系。我们 前提是通过在植入物表面上设计自组织生物活性界面， 激活经典Wnt信号通路，指导干细胞向成骨谱系分化 并改善骨整合。此外，涂层可用于再处理先前放置的植入物， 由于种植体周围炎引起的骨丢失而无法延长其使用寿命。目标1。表征稳定性， 我们的仿生界面在体内保留Wnt信号传导的时间能力使用众所周知的兔模型， 植入物行业。