Mechanoregulating HA-integrated anisotropic fibrous vessel promote AKT-sensitive and YAP-associated endothelial responses and improve regional lymphatic drainage in lymphedema.

Secondary lymphedema, characterized by localized tissue swelling caused by lymphatic damage or dysfunction, remains a major clinical challenge that compromises quality of life. Current physical therapies provide only temporary relief, underscoring the need for effective regenerative strategies. Here, we report the fabrication of a micropatterned, small-diameter fibrous artificial lymphatic vessel incorporating hyaluronic acid (HA) via electrospinning to enhance lymphatic fluid transport. The engineered scaffold exhibits optimized mechanical properties and elicits favorable cellular responses through HA-mediated biochemical cues. Lymphatic endothelial cells (LEC) cultured on the scaffold show increased expression of lymphangiogenesis-related markers, including Prox1 and LYVE-1, accompanied by AKT activation and increased VEGF-C/VEGFR3-associated marker expression. The topographical features of the scaffold were also associated with altered YAP localization and increased lymphatic endothelial marker expression. In vivo implantation of the scaffold in a rat lymphedema model reduced ankle swelling and lymphatic retention across the surgically disrupted region toward an anatomically preserved drainage basin. Collectively, these findings suggest that HA-integrated fibrous lymphatic scaffolds represent a promising strategy for lymphedema treatment by synergistically engaging biochemical and biomechanical pathways associated with lymphatic repair and functional fluid transport.

Keywords

Electrospinning, Fibrous tubular scaffolds, Lymphedema, Mechanobiology, Micropattern, Topographical cues

Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.