The Role of Cell Communication and 3D Cell-Matrix Environment in a Stem Cell-Based Tissue Engineering Strategy for Bone Repair
Date
2014-07-11
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Abstract
The use of stem cells for the repair of bone and cartilage is a primary research interest in modern tissue engineering strategies. The goal of this doctoral thesis was to investigate the role of cell communication and mechanical stimulation in a 3D tissue engineered construct, and to determine whether this construct could be optimized for bone healing. It is well established that there is an interconnected relationship between connexin-containing gap junctions, cadherins, and integrins in cell communication and the ability of cells to respond to mechanical stimulation. The specific aim of this project was to determine the role of connexin containing gap junctions and confined compression on the biosynthetic activity of embryonic
stem cells stimulated to form osteoblasts in a 3D collagen-I scaffold. Results from this project showed that this construct could be optimized for bone repair and cell differentiation could be accelerated by applying mechanical stimulation to cells at an early state of differentiation. This could be further enhanced with the application of a nitric oxide donor. As well, cell communication and the presence of functional connexin-43 gap junctions was required for lineage determination of these cells and to initiate mineralization within the construct. The necessity for cell communication was such that cells were not able to recover their function following communication inhibition. It was shown that dissociation between connexin-43 and integrin α5β1 occurred under communication impairment and could be slightly restored
with the application of nitric oxide. Thus, in order for osteoblasts to perceive a mechanical stimulus and initiate mineralization of the matrix in response, functional gap junctions and their association to integrins are required to guide cell fate and function. Under impairment of cell function, nitric oxide can be used as an exogenous factor to refocus differentiation and rescue cell function. Overall, this project helps to bridge in-vivo fracture research with basic
stem cell biology, and provides an understanding of the importance of cell communication and 3-dimensional cell-matrix environment in the healing process of bone.
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Engineering--Biomedical
Citation
Damaraju, S. (2014). The Role of Cell Communication and 3D Cell-Matrix Environment in a Stem Cell-Based Tissue Engineering Strategy for Bone Repair (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/28321