Nitric oxide-releasing hyaluronic acid therapeutics for treating periodontal disease
释放一氧化氮的透明质酸疗法用于治疗牙周病
基本信息
- 批准号:10657158
- 负责人:
- 金额:$ 46.38万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-05-01 至 2028-04-30
- 项目状态:未结题
- 来源:
- 关键词:AffectAnti-Bacterial AgentsAnti-Inflammatory AgentsAutoimmunityBiopolymersCalculiCardiovascular DiseasesCell Culture SystemCellsChronicClinicalComplexDataDevelopmentDiabetes MellitusDiseaseDisease ProgressionDoseDrug Delivery SystemsEpithelial CellsExcisionFailureFibroblastsFormulationFrequenciesGingivaGlycosaminoglycansGoalsHealthHomeostasisHumanHyaluronic AcidImmune System DiseasesImmune systemImmunityIndividualInflammationIntegration Host FactorsInterventionKineticsLigatureMacrophageMammalian CellMechanicsMicrobial BiofilmsModelingMucous MembraneNitric OxideNitric Oxide DonorsOralOsteoclastsPeriodontal DiseasesPeriodontal PocketPeriodontitisPhasePlayPrimary Cell CulturesPropertyRefractoryResearchResolutionRisk FactorsRoleSeriesStructureSurfaceSystemSystemic diseaseSystems BiologyTestingTherapeuticTherapeutic InterventionTissue ModelTissuesToxic effectTreatment Efficacyantimicrobialcytotoxicitydental biofilmdysbiosiseffective therapyefficacy evaluationhealinghuman modelimmune functionimmunoregulationimprovedin vivoin vivo evaluationinnate immune functionmacromoleculemicrobialmouse modelnanomaterialsnanoparticleneutrophiloral cavity epitheliumpatient populationperpetratorspreservationpreventprogramssubgingival biofilmsystemic inflammatory responsetherapeutic evaluationtranslational therapeuticswound healing
项目摘要
SUMMARY
Microbial plaque biofilms that form at and below the gum line are the perpetrators of periodontal diseases,
which are a class of diseases associated with non-resolving inflammation that results in soft and hard tissue
destruction. Periodontitis is characterized by an unending cycle of chronic inflammation which leads to tissue
destruction and prevents wound healing but cannot control the biofilms microbial dysbiosis. Under conditions
of systemic inflammation, these host factors are amplified leading to more severe and refractory periodontal
disease conditions. As such, periodontal diseases are affected by and can be risk factors for a number of systemic
health issues such as diabetes. Current treatment of periodontitis involves mechanical removal of supra- and
sub-gingival bacterial plaque and calculus and is often accompanied by the use of locally administered
adjunctive therapies aimed at restoring microbial homeostasis. Current adjunctive therapies do not address the
need to break the unending cycle of chronic inflammation and restore tissue homeostasis. Thus, there is a
profound need to develop an adjunctive therapeutic that: a) possesses broad-spectrum activity against biofilms
with minimal toxicity to mammalian cells; b) provides anti-inflammatory activity; and, c) promotes tissue
healing.
Due to its antibacterial and immunomodulatory functions, nitric oxide (NO) is an attractive adjunctive agent in
the treatment of periodontal diseases. In the proposed research program, we will synthesize, characterize and
evaluate nitric oxide-releasing hyaluronic acid (HA) as a multi-action NO-release system. Upon release, the
NO will serve as a broad-spectrum antibacterial and pro-wound healing agent. The macromolecule that remains
(HA) will then further serve to mitigate immunmodulation and wound healing. We will evaluate the efficacy
and associated mechanisms of this multi-action therapeutic (e.g., NO: antibacterial, HA and NO:
immunomodulatory, and NO and HA: pro-wound healing). We propose this approach will reduce the
frequency of and/or augment clinical interventions and promote improved resolution of disease. We aim to: 1)
synthesize nitric oxide-releasing hyaluronic acid nanomaterials and formulations, showing the influence of NO-
releasing HA on antibacterial and antibiofilm action, mammalian cell cytotoxicity, and inflammation in various
oral delivery formulations; 2) delineate the mechanisms modulating microbial dysbiosis, immune dysfunction
and tissue-stasis; and, 3) test in vivo therapeutic efficacy in preventing and/or halting periodontal disease
progression.
总结
在牙龈线处和牙龈线下方形成的微生物菌斑生物膜是牙周病的肇事者,
这是一类与非消退性炎症相关的疾病,
杀伤性牙周炎的特点是一个无休止的循环慢性炎症,导致组织
破坏并阻止伤口愈合,但不能控制生物膜微生物生态失调。条件下
在全身性炎症中,这些宿主因素被放大,导致更严重和难治性牙周炎。
疾病状况。因此,牙周病受多种全身性疾病的影响,并且可能是多种全身性疾病的危险因素。
健康问题,如糖尿病。目前牙周炎的治疗包括机械去除牙周膜上的
龈下菌斑和牙石,并且通常伴随着使用局部施用的
旨在恢复微生物体内平衡的连续疗法。目前的连续疗法不能解决
我们需要打破慢性炎症的无休止循环,恢复组织的稳态。由此可见,有一
对开发一种连续治疗剂的深刻需求,该治疗剂:a)具有针对生物膜的广谱活性
对哺乳动物细胞具有最小的毒性; B)提供抗炎活性;和c)促进组织
治愈
由于其抗菌和免疫调节功能,一氧化氮(NO)是一种有吸引力的促炎剂,
牙周病的治疗在拟议的研究计划中,我们将合成,表征和
评价释放一氧化氮的透明质酸(HA)作为多作用NO释放系统。释放后,
NO将用作广谱抗菌剂和促伤口愈合剂。残留下来的大分子
(HA)然后将进一步用于减轻免疫调节和伤口愈合。我们将评估
以及这种多作用治疗剂的相关机制(例如,NO:抗菌,HA和NO:
免疫调节,以及NO和HA:促进伤口愈合)。我们建议这种方法将减少
增加临床干预的频率和/或增加临床干预,并促进改善疾病的解决。我们的目标是:1)
合成释放一氧化氮的透明质酸纳米材料和制剂,显示NO-
释放HA对抗菌和抗菌膜作用、哺乳动物细胞毒性和各种炎症的影响。
口服给药制剂; 2)描述调节微生物生态失调、免疫功能障碍
和组织停滞;和,3)测试在预防和/或停止牙周病中的体内治疗功效
进展
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Mark H Schoenfisch其他文献
Mark H Schoenfisch的其他文献
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{{ truncateString('Mark H Schoenfisch', 18)}}的其他基金
Nitric oxide-releasing glycosaminoglycans for treating complex wounds
释放一氧化氮的糖胺聚糖用于治疗复杂伤口
- 批准号:
10584269 - 财政年份:2023
- 资助金额:
$ 46.38万 - 项目类别:
Role of diabetes and nitric oxide release duration on analytical performance of in vivo glucose biosensors
糖尿病和一氧化氮释放持续时间对体内葡萄糖生物传感器分析性能的作用
- 批准号:
10263316 - 财政年份:2015
- 资助金额:
$ 46.38万 - 项目类别:
Nitric oxide-releasing dendrimers for the treatment of periodontal disease
释放一氧化氮的树枝状聚合物用于治疗牙周病
- 批准号:
8927301 - 财政年份:2015
- 资助金额:
$ 46.38万 - 项目类别:
Nitric oxide-releasing dendrimers for the treatment of periodontal disease
用于治疗牙周病的释放一氧化氮的树枝状聚合物
- 批准号:
9261511 - 财政年份:2015
- 资助金额:
$ 46.38万 - 项目类别:
Role of diabetes and nitric oxide release duration on analytical performance of in vivo glucose biosensors
糖尿病和一氧化氮释放持续时间对体内葡萄糖生物传感器分析性能的作用
- 批准号:
10418787 - 财政年份:2015
- 资助金额:
$ 46.38万 - 项目类别:
Role of diabetes and nitric oxide release duration on analytical performance of in vivo glucose biosensors
糖尿病和一氧化氮释放持续时间对体内葡萄糖生物传感器分析性能的作用
- 批准号:
9185309 - 财政年份:2015
- 资助金额:
$ 46.38万 - 项目类别:
Role of diabetes and nitric oxide release duration on analytical performance of in vivo glucose biosensors
糖尿病和一氧化氮释放持续时间对体内葡萄糖生物传感器分析性能的作用
- 批准号:
10673705 - 财政年份:2015
- 资助金额:
$ 46.38万 - 项目类别:
Nitric oxide-releasing dendrimers for the treatment of periodontal disease
释放一氧化氮的树枝状聚合物用于治疗牙周病
- 批准号:
9104134 - 财政年份:2015
- 资助金额:
$ 46.38万 - 项目类别:
Nitric oxide-releasing cystic fibrosis therapeutics
释放一氧化氮的囊性纤维化疗法
- 批准号:
8968231 - 财政年份:2014
- 资助金额:
$ 46.38万 - 项目类别:
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