Synthetic hydrogels engineered to promote collecting lymphatic vessel sprouting.

ABSTRACT

The lymphatic vasculature is an essential component of the body's circulation providing a network of vessels to return fluid and proteins from the tissue space to the blood, to facilitate immune ce-ll and antigen transport to lymph nodes, and to take up dietary lipid from the intestine. The development of biomaterial-based strategies to facilitate the growth of lymphatics either for regenerative purposes or as model system to study lymphatic biology is still in its nascent stages. In particular, platforms that encourage the sprouting and formation of lymphatic networks from collecting vessels are particularly underdeveloped. Through implementation of a modular, poly(ethylene glycol) (PEG)-based hydrogel, we explored the independent contributions of matrix elasticity, degradability, and adhesive peptide presentation on sprouting of implanted segments of rat lymphatic collecting vessels. An engineered hydrogel with 680 Pa elasticity, 2.0 mM RGD adhesive peptide, and full susceptibility to protease degradability produced the highest levels of sprouting relative to other physicochemical matrix properties. This engineered hydrogel was then utilized as a scaffold to facilitate the implantation of a donor vessel that functionally grafted into the host vasculature. This hydrogel provides a promising platform for facilitating lymphangiogenesis in vivo or as a means to understand the cellular mechanisms involved in the sprout process during collecting lymphatic vessel collateralization.