title: Modeling vascularized bone regeneration within a porous biodegradable CaP scaffold loaded with growth factors.
abstract: Osteogenetic microenvironment is a complex constitution in which extracellular matrix (ECM) molecules, stem cells and growth factors each interact to direct the coordinate regulation of bone tissue development. Importantly, angiogenesis improvement and revascularization are critical for osteogenesis during bone tissue regeneration processes. In this study, we developed a three-dimensional (3D) multi-scale system model to study cell response to growth factors released from a 3D biodegradable porous calcium phosphate (CaP) scaffold. Our model reconstructed the 3D bone regeneration system and examined the effects of pore size and porosity on bone formation and angiogenesis. The results suggested that scaffold porosity played a more dominant role in affecting bone formation and angiogenesis compared with pore size, while the pore size could be controlled to tailor the growth factor release rate and release fraction. Furthermore, a combination of gradient VEGF with BMP2 and Wnt released from the multi-layer scaffold promoted angiogenesis and bone formation more readily than single growth factors. These results demonstrated that the developed model can be potentially applied to predict vascularized bone regeneration with specific scaffold and growth factors.
authors.affiliation: School of Mathematical Science, Beijing Normal University, Beijing 100875, PR China. xiaoqiangsun88@gmail.com
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Sun
authors.forename: Yunqing
authors.initials: Y
authors.lastname: Kang
authors.forename: Jiguang
authors.initials: J
authors.lastname: Bao
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yunzhi
authors.initials: Y
authors.lastname: Yang
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Zhou
mesh_terms: D001672:Biocompatible Materials / Q000494:pharmacology*; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D001861:Bone Regeneration / Q000187:drug effects*; D002130:Calcium Phosphates / Q000494:pharmacology*; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D003198:Computer Simulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects; D016062:Porosity; D062211:Spatio-Temporal Analysis; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D002130:Calcium Phosphates; D036341:Intercellular Signaling Peptides and Proteins; C020243:calcium phosphate