Nanotubes are often regarded as a precursor to nanocircuitry.  A group at UC San Diego has found that they work pretty well for transferring biological information, too.  Oh, et al. showed that selective differentiation of stem cells into bone cells could be achieved on titanium nanowires of approximately 70-100 nanometers in diameter.  Using smaller nanowires caused less selectivity and slower differentiation. This suggests that the shape of the nanowires provided a signal to metamorphose into bone cells.





The cells generated on the nanowires are osteoclasts, the bone-building half of the skeleton-maintaining bone multicellular unit.  Paired with bone-resorbing osteoclasts, the osteoblasts replace resorbed material with strong new minerals. Osteoblast creation is good news for the sufferers of osteoporosis (and perhaps newly-earthbound astronauts, as well).  Current osteoporosis drugs like biophosphonates inhibit resorption to retain bone density, but bone modeling research suggests that the mitigation of skeletal fragility will be short-term without remodeling.  Mineral replacement, not simply retainment, is key to bone integrity.

One of the most exciting discoveries in regenerative medicine has been the effect of mechanotransduction on stem cells.  The bodily stresses and strains imposed on progenitor cells prompt them to differentiate into final forms with drastically different functions. Though the precise biomolecular underpinnings of stem cell mechanotransduction are not yet understood, the results can be dramatic. Altering the shape of the cell's surrounding space by permitting the cell to spread out or constricting it can make two identical stem cells into two very different adult cells.  This was illustrated by McBeath, et al. in 2004; the image to the right shows two identical stem cells constrained within different sized wells.  Cells constrained to small globular shapes differentiated into fat cells, and their spread-out counterparts became bone cells.  

Though embryonic stem cells are often considered the most flexible differentiators, this study featured the differentiation of osteoblasts from adult mesenchymal stem cells.  Culturing replacement cells from an adult patient is useful because it sidesteps immunorejection, an inevitable consequence of most transplant therapies.  If a patient's own marrow-extracted stem cells are differentiated on nanowires, that patient will be able to incorporate the resulting osteoblasts without committing to a lifetime of immunosuppressant drugs.   

Titanium is already used by orthopedics to make prosthetic bones that are biocompatible, rugged, and perhaps just a little bit too strong- the titanium joint eventually usurps the load-bearing function of the bone around it.  When bone isn't loaded, it doesn't remodel.  Bone around an implant is eventually resorbed away, causing the implant to fit poorly within the surrounding bone.  Most orthopedic implants must be revised within 15-20 years, meaning that young recipients of new knees can expect a second operation to upgrade to a larger prosthetic. 

Sungho Jin, co-author of the paper and professor at UC San Diego's Jacobs School of Engineering, anticipates that expedited bone reconstruction through osteoblast differentiation will provide a bone-stimulating complement for existing titanium prosthetics, as well as post-traumatic bone healing. A partnership of orthopedic surgeons and engineers is already exploring the creation of nanowire-based clinical applications.  

REFERENCES:

S. Oh, et al. Stem cell fate dictated solely by altered nanotube dimension.  PNAS, January 28, 2009, doi: 10.1073/pnas.0813200106.  In press.

R. Martin, et al. A theoretical analysis of long-term bisphosphonate effects on trabecular bone volume and microdamage. Bone 2004 35:1: 296-305

R. McBeath, et al. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell, 2004, 6:483-95