Manipulation of Host Tissue to Induce a Hierarchical Microvasculature
操纵宿主组织以诱导分层微脉管系统
基本信息
- 批准号:10637683
- 负责人:
- 金额:$ 80.1万
- 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 2027-04-30
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAngiographyArchitectureBiodegradationBlood VesselsBlood flowCellsCellular InfiltrationCharacteristicsCouplingDataDevelopmentDiameterDiffusionEngineeringEtiologyExperimental DesignsExtracellular MatrixExtravasationFailureFemoral veinGelHemorrhageHistologyHydrogelsImmuneImplantIn SituIn VitroInfiltrationInvestigationLasersLinkMacrophageMethodsMicropunctureMicrosurgeryMicrotomyModificationNanoporousNeedlesOperative Surgical ProceduresOxygenPatternPerforationPerfusionPorosityProtein AnalysisPublic HealthPublishingRattusReconstructive Surgical ProceduresRegenerative MedicineRegulationResearchSideSurgeonTechnologyTestingThermographyThrombosisTissue AdhesivesTissuesTreesVascularizationangiogenesisbiomaterial compatibilitydesignfeedingfemoral arteryhydrogel scaffoldimplantationimprovedin vivoinnovationmetermimeticsneovascularizationnovel strategiesparticleregenerative approachrepairedrestorationscaffoldsoft tissuesubcutaneoustissue regeneration
项目摘要
Abstract
Reconstructive surgeons are tasked with the restoration of soft tissue loss irrespective of etiology. Over
the past two decades, hydrogel scaffolds have become a vital platform for tissue revascularization and surgical
repair. However, their slow and random vascularization upon implantation often precipitates failure and precludes
true tissue regeneration and function. Native microvascular networks are characterized by organized tree-like
branching patterns that originate from large feeding vessels. Our objective is to utilize complementary
regenerative strategies based upon rigorous preliminary data that enables the rapid development of this
hierarchical microvasculature. To achieve our objective, we recently developed an innovative microsurgical
tactic termed vascular micropuncture (MP). In this method, small perforations are created using a needle in the
recipient vasculature to facilitate cellular extravasation and angiogenesis, without causing thrombosis or
significant hemorrhage. Such induced angiogenesis can be used to randomly vascularize an adjacently placed
hydrogel scaffold, leading to perfusion within 24 h and a doubling of neovascularization. With this compelling
result, we propose to advance the MP method using an emerging in situ microengineering technology. We have
developed granular hydrogel scaffolds (GHS) based on an extracellular matrix mimetic material with controlled
microporosity that improves cell infiltration and guides vascular network formation both in vitro and in vivo.
Our hypothesis is that customized GHS can be synergistically used with MP to hasten and precisely guide
hierarchical microvascular development. To test this hypothesis, we will focus on the following three independent
specific aims: 1) To design and optimize GHS to guide microvascular development, 2) To evaluate the effect of
MP characteristics to hasten microvascular development and 3) To evaluate the coupling effects of MP and GHS
to hasten and precisely guide hierarchical microvascular development. The successful completion of these
studies should markedly improve the vascularization of scaffolds used in soft tissue reconstructive surgery. Also,
it sets the platform for further investigation in building a hierarchical microvasculature that is cornerstone to blood
flow regulation, oxygen diffusion, and immune cell modulation. Consequently, our novel approach holds
immense potential for broadly advancing regenerative medicine.
抽象的
重建外科医生的任务是恢复软组织损失,无论病因如何。超过
在过去的二十年里,水凝胶支架已成为组织血运重建和外科手术的重要平台
维修。然而,它们在植入时缓慢且随机的血管化常常会导致失败并妨碍
真正的组织再生和功能。天然微血管网络的特点是有组织的树状结构
源自大型饲养管的分支模式。我们的目标是利用互补
基于严格的初步数据的再生策略使该技术能够快速发展
分层微血管。为了实现我们的目标,我们最近开发了一种创新的显微外科手术
称为血管微穿刺(MP)的策略。在这种方法中,使用针在孔中创建小穿孔。
受体血管系统促进细胞外渗和血管生成,而不会引起血栓形成或
严重出血。这种诱导的血管生成可用于随机使相邻放置的血管化
水凝胶支架,导致 24 小时内灌注和新血管形成加倍。凭借这个引人注目的
因此,我们建议使用新兴的原位微工程技术来推进 MP 方法。我们有
开发了基于细胞外基质模拟材料的颗粒水凝胶支架(GHS)
微孔性可改善细胞浸润并引导体外和体内血管网络的形成。
我们的假设是,定制的 GHS 可以与 MP 协同使用,以加速和精确指导
分层微血管发育。为了检验这个假设,我们将重点关注以下三个独立的
具体目标:1) 设计和优化 GHS 以指导微血管发育,2) 评估效果
MP 特性可加速微血管发育,3) 评估 MP 和 GHS 的耦合效应
加速并精确指导分层微血管发育。这些工作的顺利完成
研究应显着改善软组织重建手术中使用的支架的血管化。还,
它为进一步研究构建作为血液基石的分层微脉管系统奠定了平台
流量调节、氧扩散和免疫细胞调节。因此,我们的新颖方法成立
广泛推进再生医学的巨大潜力。
项目成果
期刊论文数量(0)
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{{ truncateString('DINO J RAVNIC', 18)}}的其他基金
Diversity Supplement: Manipulation of Host Tissue to Induce a Hierarchical Microvasculature
多样性补充:操纵宿主组织以诱导分层微血管系统
- 批准号:
10851311 - 财政年份:2023
- 资助金额:
$ 80.1万 - 项目类别:
Manipulating the host-biomaterial interface for enhanced scaffold vascularization
操纵宿主-生物材料界面以增强支架血管化
- 批准号:
10644159 - 财政年份:2022
- 资助金额:
$ 80.1万 - 项目类别:
Mechanisms and Application of Micropunctured Induced Angiogenesis for the Rapid Perfusion of Intraoperative Bioprinted Flaps
微刺诱导血管生成术中生物打印皮瓣快速灌注的机制及应用
- 批准号:
10179655 - 财政年份:2021
- 资助金额:
$ 80.1万 - 项目类别:
Vascular Adaptations in Lymphocyte Transmigration
淋巴细胞迁移中的血管适应
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6934634 - 财政年份:2004
- 资助金额:
$ 80.1万 - 项目类别:
Vascular Adaptations in Lymphocyte Transmigration
淋巴细胞迁移中的血管适应
- 批准号:
6836728 - 财政年份:2004
- 资助金额:
$ 80.1万 - 项目类别:
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