Biocompatible Compound Designed to Mend Serious Leg Fractures

Northwestern University is part of a multi-institution initiative to produce "fracture putty," a biocompatible compound designed to mend serious leg fractures, such as those suffered by soldiers.

The two-year research project is funded by the Defense Advanced Research Projects Agency (DARPA), an agency of the U.S. Department of Defense.

The research team's goal is to develop a putty-like material that could be used to regenerate bones shattered by roadside bombs or other explosive devices. This type of injury, called a non-union fracture, generally will not heal in a timely manner and can lead to amputation.

Samuel Stupp, director of the Institute for BioNanotechnology in Medicine at Northwestern (IBNAM), is leading the University's portion of the research. He and Ramille Capito, a research assistant professor in Stupp's lab, will use bioactive peptide amphiphile (PA) molecules developed at IBNAM as the major bioactive component of this fracture putty to make bone regenerate.

"New technology is needed to treat in the field the devastating tissue injuries sustained by soldiers that often lead to amputation," said Stupp, Board of Trustees Professor of Materials Science and Engineering, Chemistry and Medicine. "The extremely demanding requirements of such technology could revolutionize many aspects of regenerative medicine in the civilian population."

Biomedical engineers at The University of Texas Health Science Center at Houston (UTHSC-H) are leading the overall effort, which also includes Harvard University. The total value of the UTHSC-H effort, if all phases of the development program are completed, could be up to $7.9 million with subcontract to Northwestern up to $1.2 million.

Serious injuries typically are repaired with bone grafts. Pins, plates or screws hold the grafts to healthy bone and external fixators provide support. Soldiers may require multiple surgeries and long recuperation periods, and they may not recoup full use of the injured leg.

If fracture putty proves successful, injured soldiers could fundamentally regain full use of their legs in a much shorter period of time. It could also be used in emergency rooms to treat civilians injured in traffic accidents and other traumatic events.

Northwestern investigators at IBNAM are developing the new materials based on nanotechnology to make bone regenerate quickly; the Houston group will focus on mechanical properties; and the Harvard team, led by George Whitesides, will focus on adhesion of the putty to bone.

The entire research team is being led by principal investigator Mauro Ferrari, director of the division of nanomedicine and deputy chairman of the department of biomedical engineering, a joint venture among the UT Health Science Center at Houston, The University of Texas at Austin and The University of Texas M. D. Anderson Cancer Center.

The Ferrari team will begin the pre-clinical study by testing the mechanical and biological properties of candidate compounds in mathematical models and in vitro systems. Afterward, the compounds designed in Stupp's laboratory will be tested in several animal models. If the fracture putty works in an animal model, the next step would involve patients.

"The fracture putty will serve as a bioactive scaffold and will be able to substitute for the damaged bone," said Ferrari. "At the same time, the putty will facilitate the formation of natural bone and self-healing in the surrounding soft tissue through the attraction of the patient's own stem cells. The putty will have the texture of modeling clay so that it can be molded in any shape in order to be used in many different surgical applications, including the reconnection of separated bones and the replacement of missing bones."

The research project, "BioNanoScaffolds for Post-Traumatic OsteoRegeneration," runs through December 2010. The site leaders at the other collaborating institutions are Antonios Mikos, Rice University; Bradley Weiner, The Methodist Hospital; Philip Nobel, Baylor College of Medicine; and Raffaella Righetti and Theresa Fossum, Texas A & M University.

DARPA sponsors revolutionary high-risk, high-payoff research that bridges the gap between fundamental discoveries and their military use.

"This undertaking represents the ultimate convergence of materials science, mechanics and orthopedics," said DARPA Program Manager Mitchell Zakin. "I look forward to the first results, which should present themselves in about a year or so."

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