Tissue engineering of lymphatic vessel networks with nanofibre reinforced hydrogel constructs

The lymphatic system comprises tubular vessels which transport lymph back to the blood. Injury to the lymphatic vessels including surgery or radiation therapy during cancer therapy impairs lymphatic fluid transport, with the result that interstitial fluid accumulates causing oedema and inflammation. The lack of effective therapies to address these problems highlights the need to improve understanding of lymphatic vessel development and growth, which is key to the development of novel approaches to treat this debilitating condition. While regenerative medicine has the potential to resolve lympoedema through the reconstruction of a functional lymphatic microvasculature, the organisation of endothelial cells into capillaries remains a significant challenge. The interactions between migratory lymphatic endothelial cells (LECs) and surrounding extracellular matrix (ECM) are of central importance to microvessel formation. In the present study, hydrogels were employed to study lymphatic vessel development and maintenance in vitro. Further, a simple electrospinning set up comprising two parallel collectors was used to spin-coat aligned polymer fibres, representing the elastic fibre component of the ECM, over collagen hydrogels. The resulting fibre reinforced collagen gels have been employed here to study the growth, migration and vessel formation of lymphatic endothelial cells in vitro, with the aim of elucidating the initial steps of a functional lymphatic tissue, and to serve as a model of lymphedema for use in research.The lymphatic system comprises tubular vessels which transport lymph back to the blood. Injury to the lymphatic vessels including surgery or radiation therapy during cancer therapy impairs lymphatic fluid transport, with the result that interstitial fluid accumulates causing oedema and inflammation. The lack of effective therapies to address these problems highlights the need to improve understanding of lymphatic vessel development and growth, which is key to the development of novel approaches to treat this debilitating condition. While regenerative medicine has the potential to resolve lympoedema through the reconstruction of a functional lymphatic microvasculature, the organisation of endothelial cells into capillaries remains a significant challenge. The interactions between migratory lymphatic endothelial cells (LECs) and surrounding extracellular matrix (ECM) are of central importance to microvessel formation. In the present study, hydrogels were employed to study lymphatic vessel development and maintenance in vitro. Further, a simple electrospinning set up comprising two parallel collectors was used to spin-coat aligned polymer fibres, representing the elastic fibre component of the ECM, over collagen hydrogels. The resulting fibre reinforced collagen gels have been employed here to study the growth, migration and vessel formation of lymphatic endothelial cells in vitro, with the aim of elucidating the initial steps of a functional lymphatic tissue, and to serve as a model of lymphedema for use in research