Modulation of the osteoblastic differentiation of marrow stromal cells for bone tissue engineering
type: CreativeWork
description: The clinical need for bone graft substitutes has led tissue engineering strategies to investigate strategies to create osteoconductive, osteoinductive, and osteogenic constructs for bone repair and regeneration. The strategy in this research work is to use a cell-secreted extracellular matrix (ECM) to influence the osteoblastic differentiation of marrow stromal cells (MSCs). The effects of an in vitro generated ECM on MSC osteoblastic gene expression under static culture indicated that MSCs differentiated down the osteoblastic lineage evidenced by significant increases in expression of the osteoblastic markers, such as collagen type I and osteocalcin. When cultured on an ECM, osteoblastic differentiation was accelerated and enhanced through (1) earlier upregulation of osteopontin and osteocalcin; and (2) maintenance of a high level of expression of these and other osteoblast-specific genes. The upregulation in osteoblastic gene expression leading to significant increases in calcium deposition is likely mediated through the interactions between the growth factors and other matrix molecules found in the in vitro generated ECM since the expression of insulin-like growth factor, vascular endothelial growth factor, fibromodulin, and dentin matrix protein was found to display significant peaks in expression level. To further modulate MSC differentiation, the cellular constructs were cultured in the presence of fluid shear stresses. The effects of fluid shear stress and the bioactivity of the in vitro generated ECM acted synergistically to enhance mineralized matrix deposition. However, this synergy occurred only when the constructs were cultured in the presence of dexamethasone. The spatial distribution of cells and ECM was markedly improved compared to static culture. The osteoinductive and angiogenic potential of ECM constructs generated in a flow perfusion bioreactor for different peroids of time were tested in an ectopic site in a rodent model. No osteoinduction was o…
abstract: The clinical need for bone graft substitutes has led tissue engineering strategies to investigate strategies to create osteoconductive, osteoinductive, and osteogenic constructs for bone repair and regeneration. The strategy in this research work is to use a cell-secreted extracellular matrix (ECM) to influence the osteoblastic differentiation of marrow stromal cells (MSCs). The effects of an in vitro generated ECM on MSC osteoblastic gene expression under static culture indicated that MSCs differentiated down the osteoblastic lineage evidenced by significant increases in expression of the osteoblastic markers, such as collagen type I and osteocalcin. When cultured on an ECM, osteoblastic differentiation was accelerated and enhanced through (1) earlier upregulation of osteopontin and osteocalcin; and (2) maintenance of a high level of expression of these and other osteoblast-specific genes. The upregulation in osteoblastic gene expression leading to significant increases in calcium deposition is likely mediated through the interactions between the growth factors and other matrix molecules found in the in vitro generated ECM since the expression of insulin-like growth factor, vascular endothelial growth factor, fibromodulin, and dentin matrix protein was found to display significant peaks in expression level. To further modulate MSC differentiation, the cellular constructs were cultured in the presence of fluid shear stresses. The effects of fluid shear stress and the bioactivity of the in vitro generated ECM acted synergistically to enhance mineralized matrix deposition. However, this synergy occurred only when the constructs were cultured in the presence of dexamethasone. The spatial distribution of cells and ECM was markedly improved compared to static culture. The osteoinductive and angiogenic potential of ECM constructs generated in a flow perfusion bioreactor for different peroids of time were tested in an ectopic site in a rodent model. No osteoinduction was o…
author: Pham, Quynh P.
language: eng
keywords: Biomedical engineering
date published: 2008
date modified: 2026-07-24T04:10:26Z
provider: Rice University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Rice University

PropertyValue
property ID: Handle
value: https://hdl.handle.net/1911/22275