Optimization of engineered endplates to improve in vivo integration of atissue engineered intervertebral disc
优化工程终板以改善组织工程椎间盘的体内整合
基本信息
- 批准号:10020800
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-12-01 至 2022-09-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdultAgingAlkaline PhosphataseAnimal ModelAnimalsAreaBack PainBiologicalBiological AssayBiological ProcessBiomechanicsBlood VesselsCaringCartilageClinicalClinical TreatmentConvectionDepositionDevelopmentDiffusionEconomic BurdenEngineeringFibrocartilagesGeneral PopulationGenesGeometryGoalsGrowth FactorHistologicHistologyHomeostasisHumanHyaline CartilageHydrogelsHydroxyapatitesImageImplantIn VitroInjectionsInjuryIntervertebral disc structureLabelLesionLocationLow Back PainMagnetic Resonance ImagingMechanicsMesenchymal Stem CellsMicrocapsules drug delivery systemMicrofilsMicrospheresMineralsModificationMoldsMonitorMotionNutrientOperative Surgical ProceduresOryctolagus cuniculusOsteogenesisOutcomePathologyPatientsPerformancePhysiologicalPlayPolymersProceduresProcessReactionRehabilitation therapyResearchRoleSodium ChlorideSpeedSpinalStructureSurfaceSystemTechnologyTestingThinnessTissue EngineeringTissuesTorsionTranslationsTubeUnited StatesVascular Endothelial Growth FactorsVascularizationVertebral BoneVertebral columnVeteransWeight-Bearing stateWorkactive dutyanalogbonecaprolactonecell growthchronic paincontrast enhancedcortical bonedesigndisabilitydisc regenerationfluorexonimplantationimprovedin vivoinsightinterfacialintervertebral disk degenerationmilitary veteranmineralizationneovascularizationnucleus pulposusnutritionosteogenicrelease factorrestorationscaffoldsmall moleculesocialspine bone structuretreatment strategyvertebra body
项目摘要
Low back pain, most commonly caused by degeneration of the intervertebral disc,
places a significant social and economic burden on the general public, active duty
military and veterans alike. Current clinical treatments for disc degeneration are limited
in that they do not restore disc structure or function. To address this, our group has
developed a whole, tissue engineered intervertebral disc composite (eDAPS) composed
of engineered annulus fibrosus, nucleus pulposus and endplate regions. The endplate
component, composed of an acellular porous polymer foam, is a critical aspect of the
design that forms the interface between the engineered disc and native vertebral bone,
but has yet to be optimized to promote the accelerated development of a vascularized,
boney interface. The purpose of this study is to generate design modifications to the
endplate region of the eDAPS that will accelerate integration following in vivo
implantation. We will achieve this translational goal through two Aims: Aim 1: Modify the
composition and geometry of the endplate region of the eDAPS to enhance
osteogenesis and neovascularization. In this Aim, poly(ε-caprolactone) (PCL) endplates
will be fabricated via a salt-leaching procedure with various design modifications to
promote osteogenesis and neovascularization. PDMS molds will first be used to create
macroscopic channel geometries within the endplates. Endplates will be further modified
via hydroxyapatite deposition, and the incorporation of microspheres containing vascular
endothelial growth factor (VEGF). The potential for mesenchymal stem cell osteogenesis
on the hydroxyapatite modified scaffolds will be established in vitro, via the alkaline
phosphatase assay, qPCR analysis of osteogenic genes, and histology. The bioactivity
of the VEGF released from the microsphere containing scaffolds will also be assessed in
vitro using the tube formation assay. Aim 2: Determine the effect of optimized endplate
design on the in vivo integration and nutrition of a whole tissue engineered disc
construct. In this Aim, optimized endplates will be utilized in eDAPS to be implanted in
vivo in the rabbit lumbar spine for 10 or 20 weeks. New bone and vascular formation in
the endplates following in vivo implantation will be assessed via calcein and alizarin
labelling and microFil enhanced µCT, respectively. Small molecule trans-endplate
diffusion into the engineered disc implants will be assessed via post-contrast enhanced
MRI. Integration strength of the eDAPS with the native vertebral bodies will be assessed
via tension, compression and torsional mechanical testing at physiologic loads. Animal
functional rehabilitation following eDAPS implantation will be assessed via activity
monitoring using the Motionwatch-8R, and ground reaction force mapping during
ambulation using a Tekscan system. The proposed work will advance the state-of-the art
in the field of intervertebral disc tissue-engineering, and provide insights that will speed
translation of the eDAPS technology towards clinical use.
腰痛,最常见的原因是椎间盘退变,
给广大公众、现役军人带来沉重的社会和经济负担
军人和退伍军人都一样。目前针对椎间盘退变的临床治疗方法有限
因为它们不能恢复椎间盘结构或功能。为了解决这个问题,我们小组
开发了一种完整的组织工程椎间盘复合材料(eDAPS)
工程化的纤维环、髓核和终板区域。端板
由无孔多孔聚合物泡沫组成的组件是
形成工程椎间盘和天然椎骨之间界面的设计,
但还有待优化以促进血管化的加速发展,
骨头接口。本研究的目的是对
eDAPS 的终板区域将加速体内整合
植入。我们将通过两个目标来实现这一转化目标: 目标 1:修改
eDAPS 终板区域的组成和几何形状以增强
成骨和新血管形成。为此,聚(ε-己内酯) (PCL) 端板
将通过盐浸程序制造,并进行各种设计修改
促进成骨和新血管形成。 PDMS 模具将首先用于制造
终板内的宏观通道几何形状。端板将进一步修改
通过羟基磷灰石沉积,以及掺入含有血管的微球
内皮生长因子(VEGF)。间充质干细胞成骨的潜力
羟基磷灰石修饰的支架将在体外通过碱性建立
磷酸酶测定、成骨基因的 qPCR 分析和组织学。生物活性
从含有支架的微球中释放的 VEGF 也将在
体外使用管形成试验。目标 2:确定优化终板的效果
整个组织工程椎间盘的体内整合和营养设计
构造。在此目标中,将在 eDAPS 中使用优化的终板,以植入
兔腰椎体内10或20周。新骨和血管形成
体内植入后的终板将通过钙黄绿素和茜素进行评估
分别是标记和 microFil 增强 µCT。小分子跨终板
将通过对比后增强来评估扩散到工程椎间盘植入物中的情况
核磁共振成像。将评估 eDAPS 与天然椎体的整合强度
通过生理负荷下的拉伸、压缩和扭转机械测试。动物
eDAPS 植入后的功能康复将通过活动进行评估
使用 Motionwatch-8R 进行监测,并绘制地面反作用力图
使用 Tekscan 系统进行移动。拟议的工作将推进最先进的技术
在椎间盘组织工程领域,并提供将加速
将 eDAPS 技术转化为临床应用。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
SARAH E GULLBRAND其他文献
SARAH E GULLBRAND的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('SARAH E GULLBRAND', 18)}}的其他基金
The Role of Disc Nutrition in the Etiology and Clinical Treatment of Disc Degeneration
椎间盘营养在椎间盘退变的病因学和临床治疗中的作用
- 批准号:
10311070 - 财政年份:2020
- 资助金额:
-- - 项目类别:
The Role of Disc Nutrition in the Etiology and Clinical Treatment of Disc Degeneration
椎间盘营养在椎间盘退变的病因学和临床治疗中的作用
- 批准号:
10531879 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Optimization of engineered endplates to improve in vivo integration of atissue engineered intervertebral disc
优化工程终板以改善组织工程椎间盘的体内整合
- 批准号:
10540676 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Optimization of engineered endplates to improve in vivo integration of atissue engineered intervertebral disc
优化工程终板以改善组织工程椎间盘的体内整合
- 批准号:
10624249 - 财政年份:2019
- 资助金额:
-- - 项目类别:
相似海外基金
Investigating HDAC3 phosphorylation as an epigenetic regulator of memory formation in the adult and aging brain
研究 HDAC3 磷酸化作为成人和衰老大脑记忆形成的表观遗传调节剂
- 批准号:
10752404 - 财政年份:2023
- 资助金额:
-- - 项目类别:
The Health of Aging Parents of Adult Children with Serious Conditions
患有严重疾病的成年子女的年迈父母的健康
- 批准号:
10660046 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Understanding Longer-Living Older Adult Research: The Summer Program on Aging
了解长寿老年人研究:老龄化夏季项目
- 批准号:
476343 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Role of sensory experience in the regulation of plasticity in the developing, adult and aging brain
感官体验在发育、成人和衰老大脑可塑性调节中的作用
- 批准号:
RGPIN-2019-04761 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Discovery Grants Program - Individual
Adult Cognitive and Neurobiological Indicators of Aging: Impact of Adversity and Social Support
成人衰老的认知和神经生物学指标:逆境和社会支持的影响
- 批准号:
10365348 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Adult Cognitive and Neurobiological Indicators of Aging: Impact of Adversity and Social Support
成人衰老的认知和神经生物学指标:逆境和社会支持的影响
- 批准号:
10700796 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Endogenous barcoding to determine complex dynamics of adult neurogenesis in aging and Alzheimer's disease
内源条形码确定衰老和阿尔茨海默病中成人神经发生的复杂动态
- 批准号:
10651861 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Investigating the interface of epigenetics and metabolism underlying memory formation in the adult, aging, and AD brain
研究成人、衰老和 AD 大脑中记忆形成的表观遗传学和代谢界面
- 批准号:
10420533 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Endogenous barcoding to determine complex dynamics of adult neurogenesis in aging and Alzheimer's disease
内源条形码确定衰老和阿尔茨海默病中成人神经发生的复杂动态
- 批准号:
10846200 - 财政年份:2022
- 资助金额:
-- - 项目类别:
THE DEVELOPMENT OF MECHANISM-BASED ADULT STEM CELL TREATMENTS TO COMBAT AGING PATHOLOGIES
开发基于机制的成人干细胞疗法来对抗衰老病理学
- 批准号:
10721544 - 财政年份:2022
- 资助金额:
-- - 项目类别: