Extracorporeal Shock Wave Therapy Combined with Vascular Endothelial Growth Factor-C Hydrogel for Lymphangiogenesis

Abstract

Background/Aims: Lymphedema is a clinically incurable disease that occurs commonly after lymph node dissection and/or irradiation. Several studies have recently demonstrated that extracorporeal shock wave therapy (ESWT) could promote lymphangiogenesis associated with expression of vascular endothelial growth factor (VEGF)-C. This research concerned primarily the synergistic effect of ESWT combined with VEGF-C incorporated hydrogel (VEGF-C hydrogel) combination therapy for promoting lymphangiogenesis and ultimately alleviating lymphedema. Methods: The VEGF-C hydrogel was applied to the injury site in a mouse model of lymphedema and then regularly underwent ESWT (0.05 mJ/mm², 500 shots) every 3 days for 4 weeks. Results: Four weeks after the treatment, mice treated with VEGF-C hydrogel and ESWT showed signs of the greatest decrease in edema/collagenous deposits when compared with the other experimental group. LYVE-1-positive vessels also revealed that the VEGF-C/ESWT group had significantly induced the growth of new lymphatic vessels compared to the other groups. Western blot analysis showed that expression of VEGF-C (1.24-fold) and VEGF receptor-3 (1.41-fold) was significantly increased in the VEGF-C/ESWT group compared to the normal group. Conclusion: These results suggested that VEGF-C and ESWT had a synergistic effect and were very effective in alleviating the symptoms of lymphedema and promoting lymphangiogenesis.

Alginate hydrogels allow for bioactive and sustained release of VEGF-C and VEGF-D for lymphangiogenic therapeutic applications

“…Previous work has shown that various forms of VEGF-C delivered from gelatin [41, 42] and albumin alginate [6] promoted lymphangiogenesis in vivo . However, the use of injectable and degradable binary alginate hydrogels to deliver bioactive and temporally controlled VEGF-C and VEGF-D has not been specifically tested yet.…”

Extracorporeal shockwave therapy (ESWT) ameliorates healing of tibial fracture non-union unresponsive to conventional therapy

“…To illustrate, ATP triggered ERK1/2 pathway activation improves cell proliferation and wound healing [32,33], and modulation of the inflammatory process via TLR3 [34] and other molecular signals [35,36] seem to accelerate wound healing. Biological responses induced by ESWT include angio-and lymphogenesis [36][37][38][39][40][41][42][43]; recruitment, proliferation and differentiation of endogenous stem cells [42,[44][45][46][47]; osteogenesis [48][49][50][51][52][53]. All of these are essentially involved in the initiation of the healing response, thus implicating ESWT as a highly effective modality due to its multisided target systems.…”

Cellulite and Focused Extracorporeal Shockwave Therapy for Non-Invasive Body Contouring: a Randomized Trial

“…Recently, a significant reduction of lymphedema was reported clinically following four ESWT sessions in females with secondary lymphedema following breast cancer treatment [6]. In animal experiments ESWT and the vascular endothelial growth factor (VEGF-C) hydrogel appear to exert a synergistic effect in promoting lymphangiogenesis [22]. …”