Design principles for lymphatic drainage of fluid and solutes from collagen scaffolds

Abstract

In vivo, tissues are drained of excess fluid and macromolecules by the lymphatic vascular system. How to engineer artificial lymphatics that can provide equivalent drainage in biomaterials remains an open question. This study elucidates design principles for engineered lymphatics, by comparing the rates of removal of fluid and solute through type I collagen gels that contain lymphatic vessels or unseeded channels, or through gels without channels. Surprisingly, no difference was found between the fluid drainage rates for gels that contained vessels or bare channels. Moreover, solute drainage rates were greater in collagen gels that contained lymphatic vessels than in those that had bare channels. The enhancement of solute drainage by lymphatic endothelium was more pronounced in longer scaffolds and with smaller solutes. Whole-scaffold imaging revealed that endothelialization aided in solute drainage by impeding solute reflux into the gel without hindering solute entry into the vessel lumen. These results were reproduced by computational models of drainage with a flow-dependent endothelial hydraulic conductivity. This study shows that endothelialization of bare channels does not impede the drainage of fluid from collagen gels and can increase the drainage of macromolecules by preventing solute transport back into the scaffold.

Application of microscale culture technologies for studying lymphatic vessel biology

“…The attributes of microfluidic models make them readily capable for precise quantitative analysis of the mass transport properties of the interstitium . This principle was recently demonstrated by Thompson et al where the fluid drainage properties of microengineered blind‐ended lymphatic vessels embedded within collagen scaffolds were characterized. Interestingly and somewhat surprisingly, the solute drainage rates were greater in collagen gels that contained lymphatic vessels than in those that had bare channels by preventing solute transport back into the scaffold.…”

Tissue Engineering of the Microvasculature

“…The amount of solute that remains typically decays exponentially with time, and the rate constant or half-life of this decay provides a measure of drainage (386). Measurement of drainage constants through individual lymphatics is possible (581). Individual collecting lymphatics can be cannulated for measurement of their contraction amplitudes and frequencies (161,667).…”

“…In narrower channels, ECs can form plugs, which require additional signals to promote cell migration along the channels (346). Seeding lymphatic ECs into blind-ended channels generated lymphatics (581). An alternate strategy used electrical desorption to transfer a monolayer of ECs from a thin metal rod onto a channel in collagen gel (502).…”

Biomaterial Based Strategies for Engineering New Lymphatic Vasculature

“…[108,109,184,197] Previous work has shown that collagen hydrogels can promote lymphatic vessels that can support drainage of fluid in vitro for potential regenerative tissue engineering applications. [184][185][186] Another study seeded LECs and dermal fibroblasts into collagen hydrogels where the cells were able to form lumen-forming lymphatic capillaries within the hydrogels. [190] Additionally, collagen hydrogels encapsulating a section of isolated mouse thoracic duct supported the formation of lumenized lymphatic capillaries in vitro and have applications for identifying new therapeutic and genetic lymphangiogenic regulators.…”