A novel bioengineering approach to restoring permanent periodontal inflammatory bone loss

一种恢复永久性牙周炎性骨质流失的新型生物工程方法

• 批准号: 10734465
• 负责人: Hae Lin Jang
• 金额: $ 83.41万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10734465
• 关键词: 3-Dimensional; 3D Print; Acute; Address; Affinity; Age; Allografting; Alveolar Bone Loss; American; Architecture; Area; Autologous Transplantation; Binding; Biological Factors; Biomedical Engineering; Biomimetics; Bone Cements; Bone Formation Stimulation; Bone Regeneration; Bone Transplantation; Cementation; Childhood; Chronic; Clinic; Clinical; Clinical Research; Complex; Cytoplasmic Granules; Data; Defect; Dental Implants; Development; Disease; Eating; Effectiveness; Exhibits; Failure; Feedback; Growth; Harvest; High Prevalence; Homeostasis; Human; Human body; Hydroxyapatites; Immune; Immunologics; Impairment; Implant; In Vitro; Infection; Inflammation; Inflammatory; Inflammatory Response; Injectable; Ink; Mandible; Mediating; Mediator; Medical; Methods; Minerals; Modeling; Morbidity - disease rate; Mouth Diseases; Natural regeneration; Operative Surgical Procedures; Organ; Osteitis; Osteogenesis; Pain; Pathway interactions; Patients; Periodontitis; Persons; Pharmaceutical Preparations; Procedures; Process; Production; Prognosis; Property; Public Health; Quality of life; Rattus; Regenerative capacity; Research; Research Project Grants; Resolution; Safety; Shapes; Site; Structure; Surface; Tissues; Tooth Loss; Tooth structure; Translating; Viscosity; Xenograft procedure; aging population; alveolar bone; bone; bone loss; chronic inflammatory disease; daily functioning; disease transmission; dysbiosis; early childhood; effective therapy; experience; fetal; immunoregulation; implantation; improved; in utero; infection risk; inflammatory bone loss; innovation; lipid mediator; microbiome; mimetics; nanoparticle; neutrophil; next generation; novel; novel strategies; osteogenic; particle; pathogen; peri-implantitis; preclinical study; prevent; skeletal; therapeutic effectiveness; tissue regeneration; tricalcium phosphate

About 80% of Americans experience periodontitis in their lifetime. Alveolar bone loss leads to loosening or loss of teeth or dental implants that disrupts the most basic daily functions, such as eating and speaking. Various bone grafts are being used to restore alveolar bone loss, but poor prognosis remains a long-standing problem. Autografts are considered the gold standard, but these grafts exhibit significant volume loss in inflammatory conditions. The available amount of material for autografts is limited, and surgical harvesting procedures are often complex and associated with morbidity, pain, and infection at the donor site. Allografts and xenografts have less bone formation capacity than autografts, while they are also associated with risks of infection, disease transmission, and immunological rejection by the host. Synthetic bone grafts such as hydroxyapatite (HAP) and beta-tricalcium phosphate (β-TCP) have also been widely used, mostly in granule or block form. However, none of the existing synthetic bone graft materials exhibit sufficient bone formation capacity to restore inflammatory alveolar bone loss to pre-disease levels. There is a significant unmet medical need for the development of a next-generation bone implant that can effectively regenerate alveolar bone in chronic inflammatory conditions. Alveolar bone almost never spontaneously regenerates in the presence of chronic inflammation. Excess inflammation destroys tissues and supports the growth of pathogens leading to the realization that effective control of microbiome dysbiosis in periodontitis cannot be achieved without effective control of inflammation. Inflammation can be resolved by specialized pro-resolving lipid mediators (SPMs) that can rapidly restore tissue homeostasis to stop the negative feedback loop of infection-inflammation and boost bone regeneration. SPMs effectively regulate inflammation in utero through early childhood, but their production and effectiveness diminish with age. In many instances, chronic inflammatory diseases such as periodontitis are associated with a failure of natural resolution pathways. Here, we aim to develop an innovative 3D printed customized biomimetic and immunomodulatory alveolar bone implant that can provide targeted key biological factors for inflammation modulation and bone regeneration. We will use whitlockite (WH) nanoparticles, the second most abundant bone mineral in humans with excellent bone formation capacity, to develop SPM-delivering bone-mimetic ink material for 3D printing a customized, personalized bone implant that can stably fit into alveolar bone defects to effectively resolve inflammation and boost bone regeneration. During this research project, we will establish a novel bioengineering process for preparing this innovative alveolar bone implant that can later be used by clinicians. The therapeutic effectiveness of the SPM-delivering bone-mimetic implant will be evaluated in a periodontitis model with alveolar bone loss. We envisage that the proposed biomimetic immunomodulatory 3D printed bone implant will significantly improve alveolar bone regeneration in severe inflammatory periodontitis or peri- implantitis and lead to a breakthrough in the treatment of non-healing inflammatory skeletal defects.

大约80%的美国人在他们的一生中经历牙周炎。牙槽骨丢失导致松动或丢失 牙齿或牙科植入物破坏了最基本的日常功能，如进食和说话。各种 骨移植被用于恢复牙槽骨损失，但预后差仍然是一个长期存在的问题。 自体移植物被认为是金标准，但这些移植物在炎症反应中表现出显著的体积损失。 条件用于自体移植物的材料的可用量是有限的，并且外科收获程序是不可行的。 通常是复杂的并且与供区的发病率、疼痛和感染有关。同种异体和异种移植物 骨形成能力低于自体移植物，同时它们也与感染、疾病 传播和宿主的免疫排斥。合成骨移植物，如羟基磷灰石（HAP）和 β-磷酸三钙（β-TCP）也已被广泛使用，大多数为颗粒或块状。但是没有一 的现有合成骨移植材料表现出足够的骨形成能力， 牙槽骨流失至疾病前水平。有一个显着的未满足的医疗需求的发展， 下一代骨植入物，可在慢性炎症条件下有效再生牙槽骨。 在存在慢性炎症的情况下，牙槽骨几乎不会自发再生。过量 炎症破坏组织并支持病原体的生长，导致认识到有效的 如果不有效控制炎症，就不能实现牙周炎中微生物组生态失调的控制。 炎症可以通过专门的促分解脂质介质（SPM）来解决，这些介质可以快速恢复组织 体内平衡，以阻止感染-炎症的负反馈循环，促进骨再生。SPMS 有效地调节子宫内炎症通过幼儿期，但它们的生产和有效性减少 随年龄在许多情况下，慢性炎症性疾病如牙周炎与失败有关。 自然的解决途径。在这里，我们的目标是开发一种创新的3D打印定制仿生和 可提供炎症靶向关键生物因子的免疫调节牙槽骨植入物 调节和骨再生。我们将使用白钨矿（WH）纳米粒子，第二丰富的骨 人体中具有良好骨形成能力的矿物质，以开发SPM递送仿骨墨水材料 用于3D打印定制的个性化骨植入物，可以稳定地适应牙槽骨缺损， 消除炎症和促进骨再生。在这个研究项目中，我们将建立一个新的 这是一个生物工程过程，用于制备这种创新的牙槽骨植入物，以后可供临床医生使用。 将在牙周炎中评价SPM递送仿骨种植体的治疗效果 牙槽骨丢失模型。我们设想，所提出的仿生免疫调节3D打印骨 种植体将显著改善严重炎症性牙周炎或牙周炎患者牙槽骨再生， 种植体炎，并导致在治疗非愈合性炎症性骨骼缺损的突破。