Biomaterial Based Strategies for Engineering New Lymphatic Vasculature

Abstract

The lymphatic system is essential for tissue regeneration and repair due to its pivotal role in resolving inflammation, immune cell surveillance, lipid transport, and maintaining tissue homeostasis. Loss of functional lymphatic vasculature is directly implicated in a variety of diseases, including lymphedema, obesity, and the progression of cardiovascular diseases. Strategies that stimulate the formation of new lymphatic vessels (lymphangiogenesis) could provide an appealing new approach to reverse the progression of these diseases. However, lymphangiogenesis is relatively understudied and stimulating therapeutic lymphangiogenesis faces challenges in precise control of lymphatic vessel formation. Biomaterial delivery systems could be used to unleash the therapeutic potential of lymphangiogenesis for a variety of tissue regenerative applications due to their ability to achieve precise spatial and temporal control of multiple therapeutics, direct tissue regeneration, and improve the survival of delivered cells. In this review, the authors begin by introducing therapeutic lymphangiogenesis as a target for tissue regeneration, then an overview of lymphatic vasculature will be presented followed by a description of the mechanisms responsible for promoting new lymphatic vessels. Importantly, this work will review and discuss current biomaterial applications for stimulating lymphangiogenesis. Finally, challenges and future directions for utilizing biomaterials for lymphangiogenic based treatments are considered.

Cerium-Containing Bioactive Glasses Promote In Vitro Lymphangiogenesis

“…In contrast, the Ce-MBGNs group led to remarkably enhanced tube formation in comparison to the control and MBGNs group. Moreover, the quantitative analysis of the number of formed tubes (Figure 6b) indicated that Ce-MBGNs could improve lymphatic vascular network formation to a greater extent than VEGF-C (50 ng/mL), which is a well-known growth factor able to stimulate lymphatic vascular network formation [15].…”

“…Expression of VEGFR-3 can be found in all endothelia during development, but later, VEGFR-3 becomes mainly found in lymphatic cells [15]. VEGFR-3 is thought to play a significant role in the proliferation and migration of LECs [39].…”

“…The lymphatic vascular system stems from a network of vessels that is composed of tubular-aligned lymphatic endothelial cells (LECs). LECs are the main constituent cells of the lymphatic system, and they are crucial for inflammation resolution, lipid transport, immune cell trafficking, and tissue homeostasis maintenance [14,15]. Lymphangiogenesis is a complex process that is related to the proliferation, migration, and network formation of LECs [16].…”

“…Lymphatic dysfunction can result in a variety of diseases (e.g., lymphedema, myocardial infarction) [14]. Conversely, promoting lymphatic vessel formation provides a promising strategy to reverse disease progression [15].…”

Tissue Engineering Strategies for Cancer-Related Lymphedema

“…11 Tissue engineering has witnessed remarkable advancement in various fields of medicine and has the potential of revolutionizing the management of lymphedema. [12][13][14][15][16] Combining approaches of biotechnology with the evolving understanding of lymphangiogenesis may offer promising treatment modalities for patients suffering from lymphedema. 17 This review will summarize the current approach to cancer-related lymphedema and advances in lymphatic tissue engineering strategies (Fig.…”