Mechanoregulating HA-integrated anisotropic fibrous vessel promote AKT-sensitive and YAP-associated endothelial responses and improve regional lymphatic drainage in lymphedema.
A hyaluronic acid-integrated fibrous scaffold shows promise in improving lymphatic function in a rat model of lymphedema, but human studies are needed to confirm its clinical relevance.
Where it sits
this study against the rest of the mgf (mechano growth factor) corpusSummary and findings
The study investigates the use of a hyaluronic acid-integrated fibrous scaffold to enhance lymphatic fluid transport in a rat model of lymphedema. The scaffold was shown to increase expression of lymphangiogenesis markers and reduce ankle swelling in vivo. These findings suggest potential for regenerative strategies in lymphedema management.
Abstract
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.
Background
Secondary lymphedema is a condition resulting from lymphatic damage or dysfunction, leading to localized tissue swelling and reduced quality of life. Current treatments offer only temporary relief, highlighting the need for effective regenerative solutions. This study explores the potential of a hyaluronic acid-integrated fibrous scaffold to promote lymphatic repair and improve fluid transport.
Methods
The study utilized a micropatterned, small-diameter fibrous artificial lymphatic vessel incorporating hyaluronic acid, fabricated via electrospinning. Lymphatic endothelial cells were cultured on the scaffold to assess cellular responses. An in vivo rat model of lymphedema was used to evaluate the scaffold's effectiveness in reducing ankle swelling and improving lymphatic drainage.
Results
The scaffold increased expression of lymphangiogenesis-related markers such as Prox1 and LYVE-1 in lymphatic endothelial cells. AKT activation and increased VEGF-C/VEGFR3-associated marker expression were observed. In vivo, the scaffold reduced ankle swelling and improved lymphatic drainage in the rat model.
Interpretation
The findings suggest that the hyaluronic acid-integrated scaffold can enhance lymphatic repair mechanisms in a rat model, potentially offering a new approach to lymphedema treatment. However, the clinical significance remains uncertain due to the lack of human data. Further research is needed to determine the scaffold's applicability and effectiveness in human patients.
Key findings
- Increased expression of Prox1 and LYVE-1 in lymphatic endothelial cells.
- AKT activation and increased VEGF-C/VEGFR3-associated marker expression.
- Reduced ankle swelling in a rat lymphedema model.
- Altered YAP localization associated with scaffold topography.
- Enhanced lymphatic fluid transport in vivo.
Limitations
- rat model, not human
- unknown long-term durability
- no human clinical data
- potential species-specific responses