Abstract 11422: Aligned Nanofibrillar Collagen Scaffold Guide Therapeutic Lymphangiogenic Repair in Secondary Lymphedema

Background: As a mechanical adjunct to therapeutic lymphatic repair in acquired lymphedema, we have investigated the applicability of guided lymphatic regeneration, through the introduction of a biological scaffold consisting of aligned collagen fibrils. These fibrils provide for cell attachment, alignment, and migration. Methods: We refined a large animal model using minipigs (n=16). We resected the inguinal and popliteal lymphatic system and irradiated the groin area to reproduce the conditions encountered in human cancer-related lymphedema. We assessed the status of lymphedema by detecting interstitial fluid accumulation through bioimpedance, the number of major lymphatic collectors by contrast-enhanced CT, and presence of lymphatic dermal backflow by contrast-enhanced MRI. Results: Three months after lymphatic resection and irradiation, animal subjects were randomized to: (1) scaffolds only, (2) scaffolds impregnated with VEGF-C, and (3) VEGF-C-scaffolds with additional transplantation of autologous lymph node fragments. The control group (4) did not receive any treatment. Seven animals out of 16 developed chronic lymphedema by the pre-defined bioimpedance threshold. The number of lymphatic collectors, as determined by CT, correlated with bioimpedance data. In group 1, there was slight improvement of bioimpedance ratios. In groups 2 and 4 (control), lymphedema persisted. In group 3 lymphedema was reversed in all subjects at post-Rx time-point 6 months. Macroscopic analysis of collectors in the implantation area after intradermal injection of blue dye showed newly developed lymphatic collectors aligned in the direction of the implanted collagen scaffolds. Conclusions: In this porcine acquired lymphedema model, implantation of aligned nanofibrillar collagen scaffolds facilitates the ingrowth of lymphatics across the treatment field. Moreover, simultaneous transplantation of autologous lymph node fragments improves lymphatic regeneration. The biocompatibility of these surgical approaches suggests their potential as an effective treatment option for the human disease.