Enhancing lymphangiogenesis and lymphatic drainage to vascularized lymph nodes with nanofibrillar collagen scaffolds

Abstract

Background This study investigated the effect of nanofibrillar collagen scaffold (BioBridge) implantation from the affected limb to the unaffected contralateral femoral vein or lymph node in a rat model. Methods Hind limb lymphedema in Lewis rats was created with lymphadenectomy and inguinal circumcision without radiation. The volumetric difference (greater than 5%) using computed tomography and indocyanine green fluorescence evaluated the progress of lymphedema at 4 weeks. The lymphedema rats have separated into Group I: Controls; Group II: implanted BioBridge to the contralateral femoral vein; and Group III: implanted BioBridge to the contralateral inguinal lymph node. Results A total of 14 of 30 (46.7%) rats developed hind limb lymphedema with a mean volume difference of 5.83 ± 0.99% and showed diffuse dermal backflow at 4 weeks postlymphadenectomy. Four weeks postimplantation of BioBridge, the mean volumetric difference was 5.62 ± 2.11%, 4.97 ± 0.59%, and −2.47 ± 2.37% in Group I, II, and III, respectively (p < 0.05). The dermal backflow on the affected limb increased in Groups I and II but decreased in Group III. Conclusions Implantation of BioBridge from the affected limb to the contralateral inguinal lymph node significantly reduced the hind limb lymphedema at 4 weeks.

Development of a rat model of lymphedema and the implantation of a collagen-based medical device for therapeutic intervention

“…This model causes lymphedema in 81.5% operated animals ( 24 ), provides a long-term condition of lymphedema which remains unresolved at 4 months after lymph node removal, and allows for feasibility to evaluate a range of surgical and microsurgical treatments with the portable equipment that surgeons routinely use in clinical setting (i.e., prescription magnifying glasses, NIR camera). A modification of this model omitting the irradiation resulted in lowering incidence of lymphedema by 46.7% ( 28 ).…”

“…In this methods paper, we describe and summarize our experience in generating and validating a rat hindlimb model of lymphedema. This protocol employs the established experimental design with microCT-based limb volume measurements, refines the visualization of lymph drainage with ICG imaging, and is used to evaluate the efficacy of therapeutic biomaterials and implantable medical devices ( 26 – 28 ) to improve the treatment of lymphedema.…”

Clinical Applications of Adipose-Derived Stem Cell (ADSC) Exosomes in Tissue Regeneration

“…In addition to modern surgical techniques, technology has also made significant progress through materials and scaffolds that favor the growth of new lymph vessels in vivo or in combination with free lymph node flaps. BioBridge is a collagen nanofibrous scaffold that works synergistically with lymph node transfer to promote neolymphangiogenesis [ 128 , 129 ]. Exosomes in this field, although still at an early stage, seem to be able to participate through their cargoes, such as VEGF (CD63-VEGFC fusion protein), which are transferred to the endothelial cells of the lymphatics.…”