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

• 批准号: 10637683
• 负责人: DINO J RAVNIC
• 金额: $ 80.1万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/10637683
• 关键词: Acceleration; Angiography; Architecture; Biodegradation; Blood Vessels; Blood flow; Cells; Cellular Infiltration; Characteristics; Coupling; Data; Development; Diameter; Diffusion; Engineering; Etiology; Experimental Designs; Extracellular Matrix; Extravasation; Failure; Femoral vein; Gel; Hemorrhage; Histology; Hydrogels; Immune; Implant; In Situ; In Vitro; Infiltration; Investigation; Lasers; Link; Macrophage; Methods; Micropuncture; Microsurgery; Microtomy; Modification; Nanoporous; Needles; Operative Surgical Procedures; Oxygen; Pattern; Perforation; Perfusion; Porosity; Protein Analysis; Public Health; Publishing; Rattus; Reconstructive Surgical Procedures; Regenerative Medicine; Regulation; Research; Side; Surgeon; Technology; Testing; Thermography; Thrombosis; Tissue Adhesives; Tissues; Trees; Vascularization; angiogenesis; biomaterial compatibility; design; feeding; femoral artery; hydrogel scaffold; implantation; improved; in vivo; innovation; meter; mimetics; neovascularization; novel strategies; particle; regenerative approach; repaired; restoration; scaffold; soft tissue; subcutaneous; tissue regeneration

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，而与病因无关。超过 在过去的二十年中，水凝胶支架已成为组织血运重建和手术的重要平台 维修。但是，植入后它们缓慢和随机的血管化通常会导致失败和排除 真正的组织再生和功能。天然微血管网络的特征是有组织的树状 分支模式起源于大型进食容器。我们的目标是利用补充 基于严格的初步数据的再生策略，可以快速发展 分层微脉管系统。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 策略称为血管微题（MP）。在这种方法中，使用针中的针创建了小的穿孔 受体脉管系统可促进细胞渗出和血管生成，而不会引起血栓形成或 明显的出血。这种诱导的血管生成可用于随机血管化相邻放置的 水凝胶支架，导致24小时内灌注，并增加了新血管形成。有了这个引人注目的 结果，我们建议使用新兴的原位微工程技术推进MP方法。我们有 基于细胞外基质模拟物质的开发颗粒水凝胶支架（GHS） 微孔力改善细胞浸润并指导体外和体内的血管网络形成。 我们的假设是，定制的GHS可以与MP协同使用，以加快并准确指导 分层微血管发育。为了检验这一假设，我们将重点关注以下三个独立 具体目的：1）设计和优化GHS以指导微血管发展，2）评估 MP特征加速微血管发育，3）评估MP和GHS的耦合效应 加快并精确指导分层微血管发展。这些成功完成 研究应明显改善软组织重建手术中使用的支架的血管化。还， 它为建立一个分层的微脉管系统设定了进一步研究的平台 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。