Painting Vasculature with Photosensitive Liposomes

用光敏脂质体绘制脉管系统

基本信息

批准号：
10224193
负责人：
Janeta Zoldan
金额：
$ 19.45万
依托单位：
UNIVERSITY OF TEXAS AT AUSTIN
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：
2019-09-16 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10224193
关键词：
3-Dimensional Biocompatible Materials Biophysics Blood Vessels Cell Survival Cellular Membrane Clinical Cues Development Dextrans Disease model Dorsal Encapsulated Engineering Frequencies Geometry Gold Growth Growth Factor Hydrogels In Situ In Vitro Injectable Ischemia Label Lasers Light Liposomes Maintenance Membrane Methods Modeling Monitor Mus Pattern Perfusion Photosensitivity Physiologic pulse Platelet-Derived Growth Factor Play Polysaccharides Process Regenerative capacity Role Site Skin Solid Structure System Testing Therapeutic Time Tissue Engineering Tissue Therapy Tissues Vascular Endothelial Growth Factors Vascular System Vascularization angiogenesis base blood vessel development controlled release endothelial stem cell implantation in vivo induced pluripotent stem cell macromolecule minimally invasive nanoGold nanoparticle nanoshell neovascularization organizational structure plasmonics release factor repaired spatiotemporal stem cells treatment response two-photon vasculogenesis

项目摘要

Abstract A functional vascular system is essential for the formation and maintenance of most tissues in the body. The lack of vascularization results in ischemic tissues with limited intrinsic regeneration capacity. Therefore, the ability to engineer vascular networks holds great promise in many therapeutic applications. Biomaterials can play a significant role in this process by presenting tuneable cues that can mimic the native microenvironment. However, the ability to control vascular development in a spatiotemporally-programmed manner remains a critical hurdle in this field. To this aim, we propose personalized and controlled tissue engineered neovascularization as a minimally invasive, clinically viable alternative for ischemia therapy. Our approach combines induced pluripotent stem cell-derived vascular progenitor cells (iPSC-VPCs) and light triggered release of growth factor (GF) from injectable hydrogels tailored to promote angiogenesis and vasculogenesis. To precisely control the induction of vasculogenesis in ischemic tissue, we propose synthesizing photosensitive gold nanoparticle conjugated liposomes that will release GF upon light modulation. We hypothesize that conjugating gold nanoparticles with different geometries to the membrane of multilamellar liposomes will create photosensitive microcarriers that are capable of rapidly delivering macromolecules, each at its corresponding resonance absorbance wavelength. By varying the two photon (2P) laser excitation wavelength, we will be able to actively and precisely control the spatiotemporal release of GF, allowing us to print in situ cues for blood vessel formation using light patterning. In Aim 1 we will generate photosensitive liposomes and ascertain spatiotemporal GF release via 2P light patterning. In Aim 2 we will demonstrate our light based ability to modulate iPSC-VPC vasculogenesis first in vitro and then in vivo in a dorsal skin fold chamber model in mice. The creation of light triggerable GF release system will allow us to print in situ cues for blood vessel formation using light patterning and enable precise control over formation of vasculature in 3D tissues. Such a system with superior precision and control of biophysical and spatiotemporal parameters has the potential to revolutionize current methods for creating vascularized tissue for therapy and disease modeling.

抽象的功能性血管系统对于体内大多数组织的形成和维持至关重要。这缺乏血管化导致缺血组织内在再生能力有限。因此，能力设计血管网络在许多治疗应用中具有广阔的前景。生物材料可以在这个过程中发挥重要作用，通过呈现可以模仿天然的可调节线索微环境。然而，以时空程序控制血管发育的能力方式仍然是该领域的一个关键障碍。为此，我们建议个性化和受控的组织工程化新生血管形成作为一种微创、临床上可行的缺血治疗替代方案。我们的该方法结合了诱导多能干细胞衍生的血管祖细胞（iPSC-VPC）和光触发从可注射水凝胶中释放生长因子（GF），以促进血管生成和血管发生。为了精确控制缺血组织中血管生成的诱导，我们建议合成光敏金纳米粒子缀合脂质体，在光作用下会释放GF 调制。我们假设将具有不同几何形状的金纳米颗粒与膜结合多层脂质体将产生能够快速传递的光敏微载体大分子，每个在其相应的共振吸收波长处。通过改变两个光子（2P）激光激发波长，我们将能够主动、精确地控制GF的时空释放，使我们能够使用光图案打印血管形成的原位线索。在目标 1 中，我们将生成光敏脂质体并通过 2P 光图案确定时空 GF 释放。在目标 2 中，我们将展示了我们基于光的能力，首先在体外调节 iPSC-VPC 血管生成，然后在背侧体内调节 iPSC-VPC 血管生成小鼠皮肤皱襞室模型。光触发 GF 释放系统的创建将使我们能够原位打印血管形成的线索使用光图案并能够精确控制 3D 组织中脉管系统的形成。这样的系统具有卓越的精度和对生物物理和时空参数的控制有潜力彻底改变当前为治疗和疾病建模创建血管化组织的方法。