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过牙周炎。牙槽骨丢失会导致松动或丢失 牙齿或牙科植入物会扰乱最基本的日常功能，如进食和说话。五花八门 骨移植被用来修复牙槽骨丢失，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黄金标准，但这些移植物在炎症中表现出显著的体积损失。 条件。可用于自体移植物的材料数量有限，外科手术收获程序 通常很复杂，并与供体部位的发病率、疼痛和感染有关。同种异体移植和异种移植 骨形成能力低于自体移植，但它们也与感染、疾病的风险有关 传播和宿主的免疫排斥反应。人工骨移植，如羟基磷灰石(HAP)和 β-磷酸三钙(β-TcP)也得到了广泛的应用，主要是颗粒状或块状。然而，一个也没有 现有的合成骨移植材料显示出足够的骨形成能力来恢复炎症 牙槽骨丢失恢复到疾病前的水平。有一个重大的未得到满足的医疗需求，开发一种 下一代骨植入物，可在慢性炎症条件下有效再生牙槽骨。 在慢性炎症的情况下，牙槽骨几乎不会自发再生。过剩 炎症破坏组织并支持病原体的生长，从而使人们认识到有效的 如果不能有效地控制炎症，就无法控制牙周炎中的微生物群失调。 炎症可以通过特殊的促分解脂质介质(SPM)来解决，这种介质可以快速恢复组织 动态平衡，阻止感染-炎症的负反馈循环，促进骨骼再生。SPM 通过儿童早期有效地调节子宫内的炎症，但它们的产生和有效性降低 随着年龄的增长。在许多情况下，慢性炎症性疾病如牙周炎与失败有关。 自然分解途径。在这里，我们的目标是开发一种创新的3D打印定制仿生和 可为炎症提供靶向关键生物因子的免疫调节型牙槽骨植入物 调节和骨骼再生。我们将使用白锁石(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，以开发SPM仿骨输送墨水材料 对于3D打印，定制、个性化的植入物可以稳定地适合牙槽骨缺损，从而有效地 消炎促进骨再生。在这个研究项目中，我们将建立一部小说 用于制备这种创新的牙槽骨植入物的生物工程工艺，稍后可供临床医生使用。 对牙周炎患者植入SPM仿骨种植体的疗效进行评估 牙槽骨骨质疏松模型。我们设想所提出的仿生免疫调节3D打印骨 种植体能显著促进重度炎症牙周炎或牙周组织的牙槽骨再生。 并导致在治疗不可愈合的炎症性骨缺损方面取得突破。