Painting Vasculature with Photosensitive Liposomes

摘要 一个有功能的血管系统对于体内大多数组织的形成和维持是必不可少的。这个 缺乏血管形成会导致缺血组织的内在再生能力有限。因此，这种能力 设计血管网络在许多治疗应用中具有很大的前景。 生物材料可以通过提供可调谐的线索来模仿原生生物，从而在这一过程中发挥重要作用 微环境。然而，在时空程序中控制血管发育的能力 态度仍然是这一领域的一个关键障碍。为了达到这个目的，我们提出了个性化和可控的组织 工程化新生血管作为一种微创、临床可行的缺血治疗替代方案。我们的 方法结合诱导多能干细胞来源的血管祖细胞(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 和血管生成。为了精确控制缺血组织中血管生成的诱导，我们建议 光敏纳米金结合脂质体的合成及其释放生长因子的研究 调制。我们假设将不同几何形状的金纳米粒子偶联到 多层脂质体将产生能够快速传递的光敏微载体 大分子，每个分子都在其相应的共振吸收波长。通过改变双光子(2P) 激光激发波长，我们将能够主动和精确地控制GF的时空释放， 使我们能够使用光图案在原位打印血管形成的线索。在目标1中，我们将生成 光敏脂质体，并通过2P光图案化确定时空GF释放。在《目标2》中我们将 展示我们基于光的能力，首先在体外调节IPSC-vPC血管生成，然后在体内背部 小鼠皮肤皱褶室模型。 光可触发的GF释放系统的创建将使我们能够原位打印血管形成的提示 使用光图案化，并实现对3D组织中血管形成的精确控制。这样的系统 由于生物物理和时空参数的卓越精确度和可控性， 革命性地创建用于治疗和疾病建模的血管组织的现有方法。

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.