Tuesday, February 20, 2007

Evolution of an In Vivo Bioreactor
Holt, Ginger E. et. al. Journal of Orthopedic Research. Vol. 23. 2005. 916-923.

Bone grafts are typically needed when fractures fail to mend, there is substantial bone loss after severe injury, necrosis due to avascularization, or for bone reconstruction post tumor removal (i.e. bone marrow cancer). These cases are usually treated with autogenous bone grafts. As with any implantation/transplantation, donor health (site of treatment), mechanical performance of the implant, vascularization, sterilization, and cost are critical considerations for successful treatment. To ameliorate or even alleviate these issues, the field of tissue engineering has lately been developing ideal bone graft substitutes.

There are three properties to characterize an ideal bone graft substitute: using 1) osteoconductive scaffolds, 2) osteoinductive proteins, that in turn maintain 3) osteogenic cells. Experimental implants were created using a combination of a coral exoskeleton scaffold, with and without bone morphogenic protein (BMP-2) and with or without a vascular pedicle. The bioreactors were harvested in rats. Via histology, actual bone formation (osteocytes, osteoblasts, and osteiod regions) and new vascularization only occurred in the presence of BMP-2 and a vascular pedicle (and the coral scaffold).

This paper was particularly interesting because bone formation can provide a model for the study cancer. It is believed that the same processes that occur in osteogenesis within a scaffold, cell differentiation and proliferation are very similar to that of tumor metastisis. Furthermore we talked about the use of controls and their importance in experimental design. Though seemingly having a minor effect, without the controls constructed in this experiment, key factors of bone formation could not be understood. And in turn tumor metastisis dynamics would have that much less potential for understanding.

4 comments:

An-Chi said...

There could also be the possibility of using a "cocktail" of maybe 2 or 3 growth factors. The first steps would be to figure out what the growth factors did alone concerning bone formation and then see if a combination could give even better mechanical strength and possibly improve tissue structure and function.

By the way, were the coral scaffolds degradable over time? If not, couldn't there be a problem over time as the body aged and changed but the scaffold didn't change with it?

Tran Ta said...

The study shows that vascularized bone could be formed in an isolated environment by implanting the bioreactor in rat. I'm curious that with the bone formation corresponding to the supplied nutrients, is there a way to stop the bone growth to achieve a specific size/shape inside the reactor. Besides, further mechanical testing of the new bone is needed to confirm the efficiency of the system.

todd said...

An-Chi. The scaffolds were not biodegradable. They were removed after harvesting and then the tissue was removed from inside the bioreactor, ready for implantation.

Tran Ta. Thats a good question. Controlled release of growth inhibitors? But with the scaffold they used, doing so would require a second delivery system. I think they could just easily take the new tissue and cut/shape it accordingly to the site of implantation...?t

Al Tan said...

Dude, nice paper!