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Cytokine combination therapy prediction for bone remodeling in tissue engineering based on the intracellular signaling pathway

Paper ID Volume ID Publish Year Pages File Format Full-Text
6894 524 2012 12 PDF Available
Title
Cytokine combination therapy prediction for bone remodeling in tissue engineering based on the intracellular signaling pathway
Abstract

The long-term performance of tissue-engineered bone grafts is determined by a dynamic balance between bone regeneration and resorption. We proposed using embedded cytokine slow-releasing hydrogels to tune this balance toward a desirable final bone density. In this study we established a systems biology model, and quantitatively explored the combinatorial effects of delivered cytokines from hydrogels on final bone density. We hypothesized that: 1) bone regeneration was driven by transcription factors Runx2 and Osterix, which responded to released cytokines, such as Wnt, BMP2, and TGFβ, drove the development of osteoblast lineage, and contributed to bone mass generation; and 2) the osteoclast lineage, on the other hand, governed the bone resorption, and communications between these two lineages determined the dynamics of bone remodeling. In our model, Intracellular signaling pathways were represented by ordinary differential equations, while the intercellular communications and cellular population dynamics were modeled by stochastic differential equations. Effects of synergistic cytokine combinations were evaluated by Loewe index and Bliss index. Simulation results revealed that the Wnt/BMP2 combinations released from hydrogels showed best control of bone regeneration and synergistic effects, and suggested optimal dose ratios of given cytokine combinations released from hydrogels to most efficiently control the long-term bone remodeling. We revealed the characteristics of cytokine combinations of Wnt/BMP2 which could be used to guide the design of in vivo bone scaffolds and the clinical treatment of some diseases such as osteoporosis.

Keywords
Bone tissue engineering; Bone remodeling; Cytokine combination therapy; Systems biology; Osteogenic differentiation; Signaling pathwayBMP2, bone morphogenetic protein 2; TGFβ, transforming growth factor β; Osx, Osterix; Runx2, Runt-related transcription f
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Cytokine combination therapy prediction for bone remodeling in tissue engineering based on the intracellular signaling pathway
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 33, November 2012, Pages 8265–8276
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us