title: Assessment of angiogenesis in osseointegration of a silica-collagen biomaterial using 3D-nano-CT.
abstract: Bony integration of biomaterials is a complex process in which angiogenesis plays a crucial role. We evaluated micro- and nano-CT imaging to demonstrate and quantify neovascularization in bony integration of a biomaterial and to give an image based estimation for the needed resolution for imaging angiogenesis in an animal model of femora defect healing. In 8 rats 5mm full-size defects were created at the left femur that was filled with silica-collagen bone substitute material and internally fixed with plate osteosynthesis. After 6 weeks the femora were infused in situ with Microfil, harvested and scanned for micro-CT (9 μm)(3) and nano-CT (3 μm)(3) imaging. Using those 3D images, the newly formed blood vessels in the area of the biomaterial were assessed and the total vascular volume fraction, the volume of the bone substitute material and the volume of the bone defect were quantitatively characterized. Results were complemented by histology. Differences were statistically assessed using (ANOVA). High-resolution nano-CT demonstrated new blood vessel formation surrounding the biomaterial in all animals at capillary level. Immunohistochemistry confirmed the newly formed blood vessels surrounding the bone substitute material. The mean vascular volume fraction (VVF) around the implant was calculated to be 3.01 ± 0.4%. The VVF was inversely correlated with the volume of the bone substitute material (r=0.8) but not with the dimension of the fracture zone (r=0.3). Nano-CT imaging is feasible for quantitative analysis of angiogenesis during bony integration of biomaterials and a promising tool in this context for the future.
authors: Department of Trauma Surgery, Justus-Liebig-University Giessen, Germany. volker.alt@chiru.med.uni-giessen.de
authors: Volker
authors: V
authors: Alt
authors: Daniela Vera
authors: DV
authors: Kögelmaier
authors: Katrin S
authors: KS
authors: Lips
authors: Vera
authors: V
authors: Witt
authors: Sabine
authors: S
authors: Pacholke
authors: Christian
authors: C
authors: Heiss
authors: Marian
authors: M
authors: Kampschulte
authors: Sascha
authors: S
authors: Heinemann
authors: Thomas
authors: T
authors: Hanke
authors: Ulrich
authors: U
authors: Thormann
authors: Reinhard
authors: R
authors: Schnettler
authors: Alexander C
authors: AC
authors: Langheinrich
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D018786:Bone Substitutes / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology*; D050723:Fractures, Bone / Q000000981:diagnostic imaging / Q000473:pathology; D007150:Immunohistochemistry; D036103:Nanotechnology / Q000379:methods*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D016348:Osseointegration / Q000187:drug effects*; D010477:Perfusion; D051381:Rats; D012822:Silicon Dioxide / Q000494:pharmacology*; D014057:Tomography, X-Ray Computed / Q000379:methods*
chemical_list: D001672:Biocompatible Materials; D018786:Bone Substitutes; D012822:Silicon Dioxide; D003094:Collagen