title: Aligned nanofibrillar collagen scaffolds - Guiding lymphangiogenesis for treatment of acquired lymphedema.
abstract: Secondary lymphedema is a common disorder associated with acquired functional impairment of the lymphatic system. The goal of this study was to evaluate the therapeutic efficacy of aligned nanofibrillar collagen scaffolds (BioBridge) positioned across the area of lymphatic obstruction in guiding lymphatic regeneration. In a porcine model of acquired lymphedema, animals were treated with BioBridge scaffolds, alone or in conjunction with autologous lymph node transfer as a source of endogenous lymphatic growth factor. They were compared with a surgical control group and a second control group in which the implanted BioBridge was supplemented with exogenous vascular endothelial growth factor-C (VEGF-C). Three months after implantation, immunofluorescence staining of lymphatic vessels demonstrated a significant increase in lymphatic collectors within close proximity to the scaffolds. To quantify the functional impact of scaffold implantation, bioimpedance was used as an early indicator of extracellular fluid accumulation. In comparison to the levels prior to implantation, the bioimpedance ratio was significantly improved only in the experimental BioBridge recipients with or without lymph node transfer, suggesting restoration of functional lymphatic drainage. These results further correlated with quantifiable lymphatic collectors, as visualized by contrast-enhanced computed tomography. They demonstrate the therapeutic potential of BioBridge scaffolds in secondary lymphedema.
authors.affiliation: Clinic of Plastic, Esthetic and Hand Surgery, Helios Clinic Hildesheim, Hildesheim 31135, Germany.|Clinic of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, Hannover 30625, Germany.
authors.forename: Catarina
authors.initials: C
authors.lastname: Hadamitzky
authors.affiliation: Fibralign Corporation, Union City, California 94587, USA.
authors.forename: Tatiana S
authors.initials: TS
authors.lastname: Zaitseva
authors.affiliation: Department of Radiation Oncology, Stanford University, Stanford, California 94305, USA.|Department of Physics and Astronomy, University of Victoria, Victoria, British Columbia V8P5C2, Canada.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bazalova-Carter
authors.affiliation: Fibralign Corporation, Union City, California 94587, USA.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Paukshto
authors.affiliation: Stanford Cardiovascular Institute, Stanford University, Stanford, California 94305, USA.|Center for Tissue Regeneration, Repair and Restoration, Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304, USA.
authors.forename: Luqia
authors.initials: L
authors.lastname: Hou
authors.affiliation: Center for Tissue Regeneration, Repair and Restoration, Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304, USA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Strassberg
authors.affiliation: Surpass Inc., Mountain View, California 94043, USA.
authors.forename: James
authors.initials: J
authors.lastname: Ferguson
authors.affiliation: Division of Cardiovascular Medicine, Stanford University, Stanford, California 94305, USA.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Matsuura
authors.affiliation: Division of Cardiovascular Medicine, Stanford University, Stanford, California 94305, USA.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Dash
authors.affiliation: Division of Cardiovascular Medicine, Stanford University, Stanford, California 94305, USA.
authors.forename: Phillip C
authors.initials: PC
authors.lastname: Yang
authors.affiliation: IntraOp Medical Corporation, Sunnyvale, California 94085, USA.
authors.forename: Shura
authors.initials: S
authors.lastname: Kretchetov
authors.affiliation: Clinic of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, Hannover 30625, Germany.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Vogt
authors.affiliation: Division of Cardiovascular Medicine, Stanford University, Stanford, California 94305, USA.
authors.forename: Stanley G
authors.initials: SG
authors.lastname: Rockson
authors.affiliation: Division of Cardiovascular Medicine, Stanford University, Stanford, California 94305, USA.|Center for Cardiovascular Regeneration, Houston Methodist Research Institute, Houston, Texas 77030, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Cooke
authors.affiliation: Stanford Cardiovascular Institute, Stanford University, Stanford, California 94305, USA.|Center for Tissue Regeneration, Repair and Restoration, Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304, USA.|Department of Cardiothoracic Surgery, Stanford University, Stanford, California 94305, USA.
authors.forename: Ngan F
authors.initials: NF
authors.lastname: Huang
mesh_terms: D000818:Animals; D003094:Collagen / Q000737:chemistry / Q000627:therapeutic use*; D005260:Female; D042583:Lymphangiogenesis; D008209:Lymphedema / Q000473:pathology / Q000628:therapy*; D057139:Nanofibers / Q000737:chemistry / Q000627:therapeutic use*; D013552:Swine; D013556:Swine, Miniature; D054457:Tissue Scaffolds / Q000737:chemistry*; D042582:Vascular Endothelial Growth Factor C / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D042582:Vascular Endothelial Growth Factor C; D003094:Collagen
keywords: Lymph node transplantation; Lymphangiogenesis; Lymphatic CT-imaging; Lymphatic vessel regeneration; Lymphedema; Nanofibrillar collagen scaffold; Porcine lymphedema model; VEGF-C