October 21, 2009 — While tissue engineers have made incredible strides in restoring function to many critical organs and tissues over the last decade, one organ has remained particularly elusive: bone.

Bone presents a unique challenge for tissue engineers, says Edward A. Botchwey III, Ph.D., because 'with bone, it's really important to have tissue that can not only successfully integrate with the existing tissue but also provide the strength and functionality of healthy bone.'

When a large portion of bone becomes significantly damaged or diseased, the tissue must typically be replaced either by donated bone tissue, known as an allograft, or by a synthetic bone substitute. Unfortunately, the majority of existing substitute materials currently fail upon implantation or over time. While bone allografts offer many structural and practical advantages over substitute materials, they, too, carry a high complication rate. The difficulty lies in reinvigorating the donor tissue and integrating it with the existing tissue.

Botchwey, an assistant professor of biomedical engineering and orthopaedic surgery at the University of Virginia, is helping to bring these donor bone tissues back to life. He has developed an innovative technique that could significantly improve the success rate for bone transplant procedures.

Botchwey's technique involves the application of a very thin drug-infused coating to the donor bone's external surface and throughout its internal porous network prior to the transplant procedure. Measuring just hundredths of a millimeter thick, thinner than a human hair, this coating delivers a healing agent to the bone while leaving its microscopic pores open and free to integrate with host cells.

'In successful bone regeneration, a balance is eventually established among donor and new tissue that is characteristic of healthy bone,' Botchwey says. 'We found that this balance was restored much more rapidly with our coating than with any other existing methods, making allografts much more likely to succeed.'

Botchwey developed the novel coating using molecules designed by U.Va. colleagues Timothy L. Macdonald, Ph.D., and Kevin R. Lynch, Ph.D., to mimic naturally occurring drug sphingosine-1-phosphate (S1P). While S1P had previously been shown to promote blood vessel formation, or vascularization, the researchers found it also assisted in bone allografts' ability to integrate with and adhere to existing bone.

'We've essentially developed a new system for delivering therapeutics and identified a particular drug that promotes the bone regeneration, vascularization, integration and remodeling that are so critical to a successful transplant,' Botchwey says.

The U.Va. Patent Foundation has filed a provisional patent application covering Botchwey's technology and is seeking an industrial partner to help bring it to market, which Botchwey says cannot come too soon for the 2.2 million people worldwide in need of bone graft procedures each year.

'Unfortunately, we're seeing an increasing amount of battlefield injuries that call for massive bone reconstruction,' he says. 'People suffering from these types of injuries, be they members of the military or civilians in car accidents, could benefit tremendously from this technology.'