Overview

Bone Formation through Biomineralization and Bioengineering (Postdoctoral Fellowship)

In the presence of mother of pearl (nacre), osteoblasts display altered mineralization. Round nodules are typical. The rectangular mineralization is unusual and appears to be nacre on one side and bone on the other. Photo courtesy of Ronke Olabisi, Ph.D. Click here for larger image.

Principal Investigator:
Ronke M. Olabisi, Ph.D.

Organization:
Rice University

Finding ways to mitigate or reverse bone loss in humans during spaceflight is a top priority for researchers. Dr. Ronke Olabisi is investigating nacre (mother of pearl) – the iridescent layer that forms the inside lining of many seashells – for clues into mimicking the material’s natural strength, resilience and ability to regenerate. This study of the microenvironments of bone and nacre and their impact on osteoblast function and differentiation will enable the design of biomaterials that can create or direct bone growth. Dr. Olabisi is seeking to determine if water soluble proteins in nacre cause osteoblasts to alter their behavior by building nacre in addition to bone. Investigation into the molecular signals that direct biomineralization is essential to development of self-assembled artificial bone and dentin (found in teeth).

NASA Taskbook Entry

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

To determine the differences in gene expression of osteoblasts producing bone and osteoblasts producing nacre.
To determine the different proteins in the microenvironment of osteoblasts producing nacre vs. those producing bone.
To pattern hydrogels with 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.

Earth Applications

Earth has its own host of problems concerning bone repair. Although bone is unique in the body in its capacity to repair without scar formation, there are events due to trauma, surgery, degeneration or disease that require surgical intervention and the gold standard for treatment is bone grafting. In the United States alone, over 6.3 million fractures occur annually, and of those, 550,000 require bone grafting.

This project's funding ended in 2011