Harnessing biomaterials for lymphatic system modulation.

The lymphatic system plays an integral part in regulating immune cell trafficking and the transport of macromolecules. However, its influence on disease progression and drug uptake is understood less than that of the vascular system. To bridge this knowledge gap, biomaterials can be used to investigate the lymphatic system and to provide novel understanding into complex disease processes, including cancer metastasis and inflammation. Insight gained from these mechanistic studies can be further used to design innovative biomaterials to modulate the immune system, improve drug delivery, and promote tissue regeneration. This review article focuses on recent advances in (i) biomaterials used for lymphatic vessel formation, (ii) models for studying lymphatic-immune cells interactions, (iii) pharmaceuticals and their interactions with the lymphatic system, (iv) and strategies for drug delivery via the lymphatic system. Finally, several challenges regarding adopting biomaterials for immunomodulation and future perspectives are discussed. STATEMENT OF SIGNIFICANCE: The lymphatic system plays an integral part in regulating immune cell trafficking and the transport of macromolecules. However, its influence on disease progression and drug uptake is understood less than that of the vascular system. This review article focuses on recent progresses in biomaterials to investigate the lymphatic system and to provide novel understanding into complex disease states. Insight gained from these mechanistic studies can be further used to design innovative biomaterials to modulate the immune system, improve drug delivery, and promote tissue regeneration. Finally, a number of challenges in adopting biomaterials for immunomodulation and future perspectives are discussed.