title: Chemotaxis of mesenchymal stem cells within 3D biomimetic scaffolds--a modeling approach.
abstract: Bone tissue engineering is a promising strategy to repair local defects by implanting biodegradable scaffolds which undergo remodeling and are replaced completely by autologous bone tissue. Here, we consider a Keller-Segel model to describe the chemotaxis of bone marrow-derived mesenchymal stem cells (BMSCs) into a mineralized collagen scaffold. Following recent experimental results in bone healing, demonstrating that a sub-population of BMSCs can be guided into 3D scaffolds by gradients of signaling molecules such as SDF-1α, we consider a population of BMSCs on the surface of the pore structure of the scaffold and the chemoattractant SDF-1α within the pores. The resulting model is a coupled bulk/surface model which we reformulate following a diffuse-interface approach in which the geometry is implicitly described using a phase-field function. We explain how to obtain such an implicit representation and present numerical results on μCT-data for real scaffolds, assuming a diffusion of SDF-1α being coupled to diffusion and chemotaxis of the cells towards SDF-1α. We observe a slowing-down of BMSC ingrowth after the scaffold becomes saturated with SDF-1α, suggesting that a slow release of SDF-1α avoiding an early saturation is required to enable a complete colonization of the scaffold. The validation of our results is possible via SDF-1α release from injectable carrier materials, and an adaptation of our model to similar coupled bulk/surface problems such as remodeling processes seems attractive.
authors.affiliation: Institute of Scientific Computing, Faculty of Mathematics and Natural Sciences, Technische Universität Dresden, Zellescher Weg 12-14, Dresden. Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Landsberg
authors.forename: Florian
authors.initials: F
authors.lastname: Stenger
authors.forename: Andreas
authors.initials: A
authors.lastname: Deutsch
authors.forename: Michael
authors.initials: M
authors.lastname: Gelinsky
authors.forename: Angela
authors.initials: A
authors.lastname: Rösen-Wolff
authors.forename: Axel
authors.initials: A
authors.lastname: Voigt
mesh_terms: D000818:Animals; D032701:Biomimetics; D054377:Chemokine CXCL12 / Q000378:metabolism*; D002630:Chemotactic Factors / Q000737:chemistry; D002633:Chemotaxis; D006801:Humans; D021621:Imaging, Three-Dimensional; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008855:Microscopy, Electron, Scanning / Q000379:methods; D008962:Models, Theoretical; D010006:Osteoblasts / Q000166:cytology; D015398:Signal Transduction; D023822:Tissue Engineering / Q000379:methods
chemical_list: D054377:Chemokine CXCL12; D002630:Chemotactic Factors