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% 的美国人一生中都会经历牙周炎，导致牙槽骨松动或脱落。 牙齿或牙种植体的损坏会扰乱最基本的日常功能，例如进食和说话。 骨移植被用来恢复牙槽骨丢失，但预后不良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中表现出显着的体积损失 自体移植物的可用材料数量有限，手术采集程序也很有限。 通常很复杂，与供体部位的发病、疼痛和感染有关。 骨形成能力低于自体移植物，同时也与感染、疾病的风险有关 传播和宿主的免疫排斥，例如羟基磷灰石（HAP）和 β-磷酸三钙（β-TCP）也已被广泛使用，大部分为颗粒或块状，但目前还没有。 现有的合成骨移植材料表现出足够的骨形成能力来恢复炎症 牙槽骨损失至疾病前的水平对于开发一种显着的未满足的医疗需求。 下一代骨植入物可以在慢性炎症条件下有效地再生牙槽骨。 在存在慢性炎症的情况下，牙槽骨几乎不会自发再生。 炎症会破坏组织并支持病原体的生长，从而认识到有效的 如果没有有效控制炎症，就无法控制牙周炎中的微生物群失调。 炎症可以通过专门的促消解脂质介质 (SPM) 来解决，这种介质可以快速恢复组织 体内平衡以阻止感染-炎症的负反馈循环并促进骨再生。 有效调节整个幼儿时期子宫内的炎症，但其产生和有效性会减弱 在许多情况下，牙周炎等慢性炎症性疾病与失败有关。 在这里，我们的目标是开发一种创新的 3D 打印定制仿生和 免疫调节牙槽骨植入物，可为炎症提供有针对性的关键生物因子 我们将使用白磷矿（WH）纳米颗粒，这是第二丰富的骨骼。 人体中具有优异成骨能力的矿物质，用于开发SPM传递的仿骨墨水材料 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，有效地 在这个研究项目中，我们将建立一种新型的解决炎症和促进骨骼再生的方法。 制备这种创新牙槽骨植入物的生物工程过程，以后可供种植者使用。 将评估 SPM 输送仿骨种植体在牙周炎中的治疗效果 我们设想所提出的仿生免疫调节 3D 打印骨。 种植体将显着改善严重炎症性牙周炎或牙周炎的牙槽骨再生 种植体炎，并在治疗不可愈合的炎症性骨骼缺陷方面取得了突破。