Painting Vasculature with Photosensitive Liposomes

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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.