Preclinical testing of a 3D printed external scaffold device to prevent vein graft failure after coronary bypass graft surgery
3D 打印外部支架装置预防冠状动脉搭桥手术后静脉移植失败的临床前测试
基本信息
- 批准号:10385132
- 负责人:
- 金额:$ 34.51万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-15 至 2024-09-14
- 项目状态:已结题
- 来源:
- 关键词:3-Dimensional3D PrintAddressAnimal ModelAnimal TestingAnimalsBilateralBiocompatible MaterialsBiomedical EngineeringCaliberCardiacChronicClinicalClinical ResearchCollaborationsContralateralCoronary ArteriosclerosisCoronary Artery BypassCoronary CirculationCoronary VesselsDataData AnalysesData SetDevelopmentDevice DesignsDevicesDiffuseDiseaseDoctor of MedicineDoctor of PhilosophyEngineeringFailureFollow-Up StudiesFoundationsFundingGenerationsGoalsGoldHarvestHeartHistopathologyHumanImmunohistochemistryImplantIn VitroInternationalInvestmentsLeadMechanicsMedical DeviceMedical Device DesignsMethodsModelingMorbidity - disease rateOperative Surgical ProceduresOutcomePatientsPerformancePharmacologyPhasePositioning AttributePostoperative PeriodPreclinical TestingPreventionPrintingProceduresRegulatory PathwayResearchResearch PersonnelSafetySaphenous VeinSecureSheepSmall Business Technology Transfer ResearchStenosisStimulusStressSurgeonSurgical ManagementTechniquesTestingTimeTissuesVariantVein graftbasebiodegradable scaffoldclinical practicecommercializationdesignelastomericfirst-in-humanfollow-upgraft failurehemodynamicshuman studyimmunogenicimprovedin vivoin vivo evaluationmechanical loadmechanical stimulusmortalitymultimodal datanext generationnovelpre-clinicalpreclinical studypreservationpressurepreventprofessorprototyperesponsescaffoldsheep modelstandard caresuccess
项目摘要
Saphenous vein graft (SVG) failure following coronary artery bypass grafting (CABG) is a critical clinical problem,
with recent studies revealing that as many as 25% of vein grafts develop stenosis within 12-18 months after
surgery, and up to 50% of grafts occlude within 5-10 years. CABG surgery is the gold standard treatment for
patients with severe multi-vessel disease, with over 370,000 procedures performed annually in the U.S. and
SVGs are used in 95% of cases. Identification of strategies and devices to prevent SVG failure represents a
pressing unmet clinical need. BioGraft will address this unmet need by developing an external biodegradable
scaffold device to prevent SVG failure. It is well established that mechanical loading contributes to the cellular
and structural changes leading to SVG failure. In current clinical practice, when the SVG is harvested and
implanted into the coronary circulation, it is subjected to an abrupt change in mechanical loading (20X change
in pressure, 4X change in flow-induced shear), triggering SVG wall remodeling and, often, maladaptation and
failure. Our foundational R01-funded research, which laid the scientific foundation for the founding of BioGraft,
showed that gradual increases in loading could mitigate or even eliminate graft failure. We demonstrated this
concept in vivo, showing more favorable graft adaptation with a first-generation design in an ovine model. Here,
to achieve a design that can be manufactured at scale, we propose a next-generation 3D printed biodegradable
scaffold, which we will refine and test in this proposal. To achieve our goals, we propose three specific aims. In
Aim 1, we will screen 3D-printed design candidates with ex vivo testing and degradation studies. This will allow
us to efficiently and inexpensively select designs matching desired targets. In Aim 2, we will perform pre-clinical
testing of the scaffold device in an established ovine carotid-jugular interpositional vein graft model of CABG
surgery. This will establish preliminary safety and efficacy. In Aim 3, we will characterize device performance
using mechanical testing and histopathology. These data will enable follow up fundraising, development of a
commercialization plan and initiation of FDA discussions. BioGraft’s founding team leverages a long-standing
engineering and clinical collaboration and recent partnerships with renowned investigators at Stanford and Duke
who hold IP for unique bioabsorbable materials and bring expertise in rapid 3D printing manufacturing methods.
We see a potential annual $1.6B total addressable market for the proposed device.
冠状动脉旁路移植术(CABG)后大隐静脉移植物(SVG)失效是一个严重的临床问题,
最近的研究表明,多达25%的静脉移植物在移植后12-18个月内发生狭窄,
手术,高达50%的移植物在5-10年内闭塞。冠状动脉旁路移植术是金标准治疗,
严重多支血管疾病患者,美国每年进行超过370,000例手术,
SVG在95%的情况下使用。识别防止SVG故障的策略和设备代表了
未满足的临床需求。BioGraft将通过开发一种外部可生物降解的
脚手架装置,以防止SVG故障。众所周知,机械负荷有助于细胞的生长。
以及导致SVG故障的结构变化。在当前的临床实践中,当SVG被采集并且
植入冠状动脉循环后,它会受到机械负荷的突然变化(20倍变化
在压力,4倍的变化,在流动引起的剪切),触发SVG壁重塑,往往是适应不良,
失败我们的基础R 01资助的研究,为BioGraft的成立奠定了科学基础,
表明逐渐增加负荷可以减轻甚至消除移植失败。我们证明了这一点
概念在体内,表现出更有利的移植物适应与第一代设计在绵羊模型。在这里,
为了实现可以大规模制造的设计,我们提出了下一代3D打印可生物降解的
scaffold,我们将在本提案中对其进行改进和测试。为了实现我们的目标,我们提出了三个具体目标。在
目标1,我们将通过体外测试和降解研究筛选3D打印的候选设计。这将允许
我们可以有效地和廉价地选择设计匹配所需的目标。在目标2中,我们将进行临床前
支架装置在建立的羊颈动脉-颈静脉间置静脉移植物CABG模型中的测试
手术这将确定初步的安全性和有效性。在目标3中,我们将描述器械性能
使用机械测试和组织病理学。这些数据将使后续筹款,发展
商业化计划和启动FDA讨论。BioGraft的创始团队充分利用了
工程和临床合作,以及最近与斯坦福大学和杜克著名研究人员的合作
他们拥有独特的生物可吸收材料的知识产权,并在快速3D打印制造方法方面拥有专业知识。
我们看到拟议设备的潜在年度可寻址市场总额为16亿美元。
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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Alison L Marsden其他文献
Alison L Marsden的其他文献
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{{ truncateString('Alison L Marsden', 18)}}的其他基金
Computational Medicine in the Heart, Integrated Training Program
心脏计算医学综合培训计划
- 批准号:
10556918 - 财政年份:2023
- 资助金额:
$ 34.51万 - 项目类别:
SCH: INT: A Virtual Surgery Simulator to Accelerate Medical Training in Cardiovascular Disease
SCH:INT:加速心血管疾病医疗培训的虚拟手术模拟器
- 批准号:
10412769 - 财政年份:2019
- 资助金额:
$ 34.51万 - 项目类别:
SCH: INT: A Virtual Surgery Simulator to Accelerate Medical Training in Cardiovascular Disease
SCH:INT:加速心血管疾病医疗培训的虚拟手术模拟器
- 批准号:
10487534 - 财政年份:2019
- 资助金额:
$ 34.51万 - 项目类别:
SCH: INT: A Virtual Surgery Simulator to Accelerate Medical Training in Cardiovascular Disease
SCH:INT:加速心血管疾病医疗培训的虚拟手术模拟器
- 批准号:
10259714 - 财政年份:2019
- 资助金额:
$ 34.51万 - 项目类别:
Automated data curation to ensure model credibility in the Vascular Model Repository
自动数据管理以确保血管模型存储库中模型的可信度
- 批准号:
10175029 - 财政年份:2019
- 资助金额:
$ 34.51万 - 项目类别:
SCH: INT: A Virtual Surgery Simulator to Accelerate Medical Training in Cardiovascular Disease
SCH:INT:加速心血管疾病医疗培训的虚拟手术模拟器
- 批准号:
10020975 - 财政年份:2019
- 资助金额:
$ 34.51万 - 项目类别:
Automated data curation to ensure model credibility in the Vascular Model Repository
自动数据管理以确保血管模型存储库中模型的可信度
- 批准号:
10016840 - 财政年份:2019
- 资助金额:
$ 34.51万 - 项目类别:
Enabling reliable cardiovascular simulations via uncertainty quantification
通过不确定性量化实现可靠的心血管模拟
- 批准号:
9030537 - 财政年份:2016
- 资助金额:
$ 34.51万 - 项目类别:
Enabling reliable cardiovascular simulations via uncertainty quantification
通过不确定性量化实现可靠的心血管模拟
- 批准号:
9348646 - 财政年份:2016
- 资助金额:
$ 34.51万 - 项目类别:
Enabling reliable cardiovascular simulations via uncertainty quantification
通过不确定性量化实现可靠的心血管模拟
- 批准号:
9751081 - 财政年份:2016
- 资助金额:
$ 34.51万 - 项目类别:
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