Overview
Contribution of the Vestibular and Sympathetic Nervous Systems to Space-Induced Bone Loss (Postdoctoral Fellowship)
Principal Investigator:
Guillaume Vignaux, Ph.D.
Organization:
Vanderbilt University Medical Center
Technical Summary
Understanding the signals that direct biomineralization is paramount for successful synthesis of self-assembled artificial bone and dentin biomimetic materials. Bone and seashell are biominerals shown to undergo both whole cell and single protein directed biomineralization. Furthermore, mammalian osteoblasts have been shown to produce shell-like structures in the presence of shells. Bone and nacre chips with no growth factors incubated with osteoblasts demonstrated biomineralization in the intervening gap: new bone near the bone chip and new nacre near the nacre chip. Understanding the concomitant changes in the microenvironment and their impact on osteoblast function and differentiation will enable the design of biomaterials that can create or direct specific functions.
The hypothesis of this project is that water soluble proteins from seashell mother of pearl (nacre) cause osteoblasts to build bone and nacre. Nacre-initiated osteogenesis occurs in vivo, but not the production of new nacre. Despite its osteogenicity, nacre is not widely used as an implant material due to its limited dimensions and in vivo results that vary with preparation procedures. Regardless, nacre's presence changes the cellular microenvironment and causes functional changes in mammalian osteoblasts that direct them to build mollusk shell material. This behavior does not occur with the geological or synthetic mineral comprising nacre (aragonite), supporting our hypothesis that soluble factors are responsible. Nacre provides a model for engineering such factors into biomaterials.
Specific Aims
1. To determine the differences in gene expression of osteoblasts producing bone and osteoblasts producing nacre.
2. To determine the different proteins in the microenvironment of osteoblasts producing nacre vs. those producing bone.
3. To pattern hydrogels with and N40 Dentin Matrix Protein 1 (DMP1), a hydroxyapatite nucleation protein in bone and dentin, and Nacre 40 (N40), an aragonite nucleation protein in nacre to direct biomineralization in desired patterns.
The hypothesis of this project is that water soluble proteins from seashell mother of pearl (nacre) cause osteoblasts to build bone and nacre. Nacre-initiated osteogenesis occurs in vivo, but not the production of new nacre. Despite its osteogenicity, nacre is not widely used as an implant material due to its limited dimensions and in vivo results that vary with preparation procedures. Regardless, nacre's presence changes the cellular microenvironment and causes functional changes in mammalian osteoblasts that direct them to build mollusk shell material. This behavior does not occur with the geological or synthetic mineral comprising nacre (aragonite), supporting our hypothesis that soluble factors are responsible. Nacre provides a model for engineering such factors into biomaterials.
Specific Aims
1. To determine the differences in gene expression of osteoblasts producing bone and osteoblasts producing nacre.
2. To determine the different proteins in the microenvironment of osteoblasts producing nacre vs. those producing bone.
3. To pattern hydrogels with and N40 Dentin Matrix Protein 1 (DMP1), a hydroxyapatite nucleation protein in bone and dentin, and Nacre 40 (N40), an aragonite nucleation protein in nacre to direct biomineralization in desired patterns.
This project's funding ended in 2013