Painting Vasculature with Photosensitive Liposomes

摘要 一个功能性的血管系统对于身体中大多数组织的形成和维持是必不可少的。的 缺乏血管形成导致缺血组织具有有限的内在再生能力。因此，能力 设计血管网络在许多治疗应用中具有很大的前景。 生物材料可以在这一过程中发挥重要作用，通过呈现可调节的线索，可以模仿天然的 微环境然而，在时空程序化的血管发育中控制血管发育的能力， 在这一领域，态度仍然是一个关键障碍。为了实现这一目标，我们提出了个性化和可控的组织 作为局部缺血治疗的微创、临床上可行的替代方案的工程化新血管形成。我们 方法结合诱导多能干细胞衍生的血管祖细胞（iPSC-VPC）和 光触发生长因子（GF）从定制的可注射水凝胶释放以促进血管生成 和血管生成。为了精确地控制缺血组织中血管发生的诱导，我们建议 合成光敏金纳米颗粒缀合的脂质体，其将在光下释放GF 调变我们假设，将具有不同几何形状的金纳米颗粒结合到细胞膜上， 多层脂质体将产生光敏微载体， 大分子，每个在其相应的共振吸收波长。通过改变双光子（2 P） 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， 让我们可以利用光的图案来打印血管形成的原位线索。在目标1中，我们将生成 光敏脂质体和确定时空GF释放通过2 P光图案。在目标2中， 证明了我们基于光的能力，首先在体外然后在背侧动脉中在体内调节iPSC-VPC血管发生。 小鼠皮肤褶皱室模型。 光致变色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 使用光图案化并且能够精确控制3D组织中脉管系统的形成。这种系统 具有上级精度和生物物理和时空参数的控制， 革命性地改变目前的方法，用于创建用于治疗和疾病建模的血管化组织。

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.