Devices for Treating Inflammatory Bone Loss in an Oral Environment

用于治疗口腔环境中炎症性骨质流失的装置

• 批准号: 7857987
• 负责人: DAVID A. PULEO
• 金额: $ 40.69万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7857987
• 关键词: Acute; Acute suppurative arthritis due to bacteria; Affect; Anti-Bacterial Agents; Anti-Inflammatory Agents; Anti-inflammatory; Antibiotics; Bacteria; Biocompatible Materials; Biological; Bone Regeneration; Bone Resorption; Canis familiaris; Catabolic Process; Cells; Connective Tissue; Cyst; Data; Defect; Dental; Dental Implants; Development; Device or Instrument Development; Devices; Disease; Effectiveness; Ensure; Environment; Enzymes; Event; Goals; Heart; Human; Implant; In Vitro; Individual; Indolent; Infection; Inflammation; Inflammatory; Inflammatory Response; Joints; Kinetics; Lead; Light; Literature; Location; Mediator of activation protein; Mesenchymal; Methods; Microbe; Modeling; Natural regeneration; Operative Surgical Procedures; Oral; Oral cavity; Organism; Orthopedics; Osteoblasts; Osteoclasts; Osteogenesis; Osteolysis; Osteomyelitis; Outcome; Periodontitis; Pharmaceutical Preparations; Phase; Play; Pluronics; Polymers; Process; Production; Property; Reaction; Role; Sequential Treatment; Site; Structure; Surface; System; Testing; Tissues; Tooth structure; Ursidae Family; Work; Wound Healing; antimicrobial; bactericide; base; bone; bone loss; cellulose acetate phthalate; combat; connective tissue metabolism; controlled release; cytokine; design; implantable device; in vivo; killings; microbial; multidisciplinary; osteoblast differentiation; particle; peri-implantitis; progenitor; public health relevance; regenerative; repaired; soft tissue; tissue regeneration; treatment strategy

DESCRIPTION (provided by applicant): An association between infection and suboptimal regenerative outcomes has often been described in the periodontal and oral surgical literature. It is also increasingly recognized that low-level bacterial contamination can play a role in "aseptic" loosening of total joint implants. In this context, the term "infection" does not refer to fulminating, acute processes, but to subclinical, indolent infections characterized by colonization of substrates. In these conditions, microbial contaminants initiate synthesis of potent pro-inflammatory cytokines by local cells. These primary mediators, in turn, stimulate production of secondary mediators that amplify the inflammatory response. The end result is secretion of tissue-degrading enzymes and eventually osteoclastic bone resoprtion. In this project, a multidisciplinary team approach will be used to develop proactive, multifunctional devices for localized bone regeneration in sites compromised by oral microbes by attacking the problems of microbial contamination, inflammation, tissue destruction, and hindered tissue repair. In Aim 1, a controlled release system for sequential delivery of multiple biomolecules will be developed. With respect to this Aim, it is hypothesized that the devices can be tailored to deliver antibacterial, anti-inflammatory, anticatabolic, and anabolic compounds with discrete profiles that ensure appropriate bioactivity. In Aim 2, devices selected from Aim 1 will be investigated for their ability to control microbial bioburden and inflammation as well as to inhibit bone resorption and to promote bone formation in vitro, and material degradation and drug release will be correlated with in vivo findings. It is hypothesized that biomolecules released from the devices will kill oral microbes, decrease osteoclastic differentiation/activity, and increase osteoblastic differentiation/activity. In Aim 3, complete devices providing individual, sequential, combined, and simultaneous drug release profiles will be tested for their biological activity in vivo using a canine peri- implantitis model. It is hypothesized that sequential treatment of the different phases of the disease process with a unitary device will be more effective than the common approach of treating only one of the components. The findings of these studies will contribute to understanding of the chain of biological events that occurs during bacterially-induced inflammatory bone destruction, and they will progress the field of biomedical device development toward more effective means for enhancing bone regeneration in an oral microbial environment. PUBLIC HEALTH RELEVANCE: Colonization of natural and synthetic biomaterials by bacteria elicits a cascade of local tissue reactions that ultimately lead to loss of the supportive structures. Such tissue destruction is at the heart of many conditions, including infected teeth, bones, dental implants, and joint implants. This project will develop multifunctional, unitary, controlled release devices that halt the detrimental processes and stimulate localized tissue repair in sites compromised by bacteria.

描述(由申请人提供)：牙周和口腔外科文献中经常描述感染和次优再生结果之间的联系。越来越多的人认识到，低水平的细菌污染可以在全关节植入物的无菌松动中发挥作用。在这种情况下，“感染”一词不是指暴发的、急性的过程，而是指以底物定植为特征的亚临床、惰性感染。在这些条件下，微生物污染物会启动局部细胞合成强有力的促炎细胞因子。这些初级介质反过来刺激次级介质的产生，从而放大炎症反应。最终结果是分泌组织降解酶，最终导致破骨细胞骨再吸收。在这个项目中，将使用多学科团队的方法来开发主动的、多功能的设备，通过解决微生物污染、炎症、组织破坏和受阻的组织修复等问题，在受到口腔微生物危害的部位进行局部骨再生。在目标1中，将开发一种用于顺序递送多个生物分子的控释系统。关于这一目标，可以假设这些设备可以定制成提供具有离散轮廓的抗菌、抗炎、抗代谢和合成化合物，以确保适当的生物活性。在目标2中，将研究从目标1中选择的设备在体外控制微生物生物堵塞和炎症以及抑制骨吸收和促进骨形成的能力，材料降解和药物释放将与体内的研究结果相关。据推测，从设备中释放的生物分子将杀死口腔微生物，降低破骨细胞的分化/活性，并增加成骨细胞的分化/活性。在目标3中，提供单独、顺序、组合和同时药物释放曲线的完整设备将使用犬种植体周围炎模型在体内测试其生物活性。据推测，使用单一设备对疾病过程的不同阶段进行顺序治疗将比仅治疗其中一种成分的常见方法更有效。这些研究的结果将有助于理解细菌诱导的炎症性骨破坏过程中发生的一连串生物事件，并将推动生物医学设备开发领域朝着更有效的手段促进口腔微生物环境中的骨再生。与公共卫生相关：细菌对天然和合成生物材料的定植引发了一连串的局部组织反应，最终导致支持结构的丧失。这种组织破坏是许多疾病的核心，包括感染的牙齿、骨骼、牙科植入物和关节植入物。该项目将开发多功能、单一、受控释放装置，停止有害过程，并刺激受细菌危害部位的局部组织修复。

项目成果

Comparison of sequential drug release in vitro and in vivo.

体外和体内连续药物释放的比较。

• DOI: 10.1002/jbm.b.33472
• 发表时间: 2016
• 期刊: Journal of biomedical materials research. Part B, Applied biomaterials
• 作者: Sundararaj,SharathC;Al-Sabbagh,Mohanad;Rabek,CherylL;Dziubla,ThomasD;Thomas,MarkV;Puleo,DavidA
• 通讯作者: Puleo,DavidA

Drug release from calcium sulfate-based composites.

• DOI: 10.1002/jbm.b.33181
• 发表时间: 2015-01
• 期刊: JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
• 影响因子: 3.4
• 作者: Orellana, Bryan R.;Hilt, J. Zach;Puleo, David A.
• 通讯作者: Puleo, David A.

Combined Effects of Drugs and Plasticizers on the Properties of Drug Delivery Films.

• DOI: 10.1177/0883911515627178
• 发表时间: 2016-07
• 期刊: Journal of bioactive and compatible polymers
• 影响因子: 1.7
• 作者: Jennings CL;Dziubla TD;Puleo DA
• 通讯作者: Puleo DA

Tailored sequential drug release from bilayered calcium sulfate composites.

从双层硫酸钙复合材料中定制的连续药物释放。

• DOI: 10.1016/j.msec.2014.06.044
• 发表时间: 2014
• 期刊: Materials science & engineering. C, Materials for biological applications
• 作者: Orellana,BryanR;Puleo,DavidA
• 通讯作者: Puleo,DavidA

Design of a multiple drug delivery system directed at periodontitis.

• DOI: 10.1016/j.biomaterials.2013.07.093
• 发表时间: 2013-11
• 期刊: BIOMATERIALS
• 影响因子: 14
• 作者: Sundararaj, Sharath C.;Thomas, Mark V.;Peyyala, Rebecca;Dziubla, Thomas D.;Puleo, David A.
• 通讯作者: Puleo, David A.