title: Poly-ε-caprolactone Coated and Functionalized Porous Titanium and Magnesium Implants for Enhancing Angiogenesis in Critically Sized Bone Defects.
abstract: For healing of critically sized bone defects, biocompatible and angiogenesis supporting implants are favorable. Murine osteoblasts showed equal proliferation behavior on the polymers poly-ε-caprolactone (PCL) and poly-(3-hydroxybutyrate)/poly-(4-hydroxybutyrate) (P(3HB)/P(4HB)). As vitality was significantly better for PCL, it was chosen as a suitable coating material for further experiments. Titanium implants with 600 µm pore size were evaluated and found to be a good implant material for bone, as primary osteoblasts showed a vitality and proliferation onto the implants comparable to well bottom (WB). Pure porous titanium implants and PCL coated porous titanium implants were compared using Live Cell Imaging (LCI) with Green fluorescent protein (GFP)-osteoblasts. Cell count and cell covered area did not differ between the implants after seven days. To improve ingrowth of blood vessels into porous implants, proangiogenic factors like Vascular Endothelial Growth Factor (VEGF) and High Mobility Group Box 1 (HMGB1) were incorporated into PCL coated, porous titanium and magnesium implants. An angiogenesis assay was performed to establish an in vitro method for evaluating the impact of metallic implants on angiogenesis to reduce and refine animal experiments in future. Incorporated concentrations of proangiogenic factors were probably too low, as they did not lead to any effect. Magnesium implants did not yield evaluable results, as they led to pH increase and subsequent cell death.
authors.affiliation: Small Animal Clinic, University of Veterinary Medicine Hannover, Foundation, Hannover D-30559, Germany. laura.roland@tiho-hannover.de.|Division of Medicine Clinic III, Hematology, Oncology and Palliative Medicine, University of Rostock, Rostock D-18057, Germany. laura.roland@tiho-hannover.de.
authors.forename: Laura
authors.initials: L
authors.lastname: Roland
authors.affiliation: Small Animal Clinic, University of Veterinary Medicine Hannover, Foundation, Hannover D-30559, Germany. michael.grau@tiho-hannover.de.|Division of Medicine Clinic III, Hematology, Oncology and Palliative Medicine, University of Rostock, Rostock D-18057, Germany. michael.grau@tiho-hannover.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Grau
authors.affiliation: Small Animal Clinic, University of Veterinary Medicine Hannover, Foundation, Hannover D-30559, Germany. julia.matena@tiho-hannover.de.
authors.forename: Julia
authors.initials: J
authors.lastname: Matena
authors.affiliation: Institute for Biomedical Engineering, Rostock University Medical Center, Rostock D-18119, Germany. michael.teske@uni-rostock.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Teske
authors.affiliation: Materials and Processes Department, Laser Zentrum Hannover e. V., Hannover D-30419, Germany. m.gieseke@lzh.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Gieseke
authors.affiliation: Clinic for Cranio-Maxillo-Facial Surgery, Hannover Medical School, Hannover D-30625, Germany. kampmann.andreas@mh-hannover.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kampmann
authors.affiliation: Institute for Biometry, Epidemiology and Information Processing, University of Veterinary Medicine Hannover, Foundation, Hannover D-30559, Germany. martin.beyerbach@tiho-hannover.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Beyerbach
authors.affiliation: Small Animal Clinic, University of Veterinary Medicine Hannover, Foundation, Hannover D-30559, Germany. hugo.murua.escobar@med.uni-rostock.de.|Division of Medicine Clinic III, Hematology, Oncology and Palliative Medicine, University of Rostock, Rostock D-18057, Germany. hugo.murua.escobar@med.uni-rostock.de.
authors.forename: Hugo
authors.initials: H
authors.lastname: Murua Escobar
authors.affiliation: Institut fuer Werkstoffkunde, Leibniz Universitaet Hannover, Garbsen D-30823, Germany. haferkamp@iw.uni-hannover.de.
authors.forename: Heinz
authors.initials: H
authors.lastname: Haferkamp
authors.affiliation: Clinic for Cranio-Maxillo-Facial Surgery, Hannover Medical School, Hannover D-30625, Germany. gellrich.nils-claudius@mh-hannover.de.
authors.forename: Nils-Claudius
authors.initials: NC
authors.lastname: Gellrich
authors.affiliation: Small Animal Clinic, University of Veterinary Medicine Hannover, Foundation, Hannover D-30559, Germany. ingo.nolte@tiho-hannover.de.
authors.forename: Ingo
authors.initials: I
authors.lastname: Nolte
mesh_terms: D000818:Animals; D000069343:Bone-Implant Interface / Q000098:blood supply*; D002460:Cell Line; D002478:Cells, Cultured; D024243:HMGB1 Protein / Q000494:pharmacology; D006885:Hydroxybutyrates / Q000009:adverse effects / Q000494:pharmacology; D008274:Magnesium / Q000009:adverse effects / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D016348:Osseointegration; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology; D011091:Polyesters / Q000009:adverse effects / Q000494:pharmacology*; D016062:Porosity; D014025:Titanium / Q000009:adverse effects / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D000094122:Polyhydroxybutyrates
chemical_list: D024243:HMGB1 Protein; D006885:Hydroxybutyrates; D008274:Magnesium; D011091:Polyesters; D014025:Titanium; D042461:Vascular Endothelial Growth Factor A; C068056:poly(3-hydroxybutyrate-co-4-hydroxybutyrate); D000094122:Polyhydroxybutyrates; C016240:polycaprolactone
keywords: HMGB1; VEGF; angiogenesis; poly-(3-hydroxybutyrate)/poly-(4-hydroxybutyrate); poly-ε-caprolactone; titanium implants