title: Simulation of cell differentiation in fracture healing: mechanically loaded composite scaffolds in a novel bioreactor system.
abstract: Cell differentiation during bone healing following a fracture is influenced by various biological and mechanical factors. We introduce a method for the examination of cell and tissue differentiation simulating a fracture gap in vitro. A closed bioreactor system allows the imitation of the biological, mechanical, and biochemical conditions in vitro. The initial hematoma formed in a fracture is simulated with a mixed construct composed of lyophilized cancellous bone and a fibrin matrix in a sandwich configuration. The construct may be loaded with osteoprogenitor cells. Exemplarily, constructs were loaded with rabbit periosteal cells and cultivated under mechanical loading with 7 kPa at 0.05 Hz for up to two weeks. During the observation period, cell morphology and correlating protein synthesis changed under mechanical stimulation. Cell differentiation differed between the various regions of the constructs. The periosteal cells were arranged perpendicularly to the mechanical loading and differentiated to osteoblastic forms with rising collagen type I synthesis, constant alkaline phosphatase activity, and initiation of the calcification of the extracellular matrix. The observed pattern of cell and tissue differentiation was similar to the one seen in the early phase of bone healing. In conclusion, the presented method allows simulation of cell and tissue differentiation during the early phase of fracture healing. It could serve as an in vitro model for the examination of mechanical and pharmacological influences during the early phase of bone healing on a cellular level.
authors.affiliation: Center for Musculoskeletal Surgery, Charité-University Medicine Berlin, Free and Humboldt-University of Berlin, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Matziolis
authors.forename: Jens
authors.initials: J
authors.lastname: Tuischer
authors.forename: Grit
authors.initials: G
authors.lastname: Kasper
authors.forename: Mark
authors.initials: M
authors.lastname: Thompson
authors.forename: Barbara
authors.initials: B
authors.lastname: Bartmeyer
authors.forename: Dörte
authors.initials: D
authors.lastname: Krocker
authors.forename: Carsten
authors.initials: C
authors.lastname: Perka
authors.forename: Georg
authors.initials: G
authors.lastname: Duda
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D019149:Bioreactors; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D017102:Fracture Healing / Q000502:physiology*; D010006:Osteoblasts / Q000166:cytology*; D011817:Rabbits; D013234:Stem Cells / Q000166:cytology*
chemical_list: D001672:Biocompatible Materials