OREF grant spurs bone substitute research

The primary goal of the Orthopaedic Research and Education Foundation (OREF) Research Grant is to provide seed money to a new clinician scientist. In effect, this grant is an investment both in the investigator and in an idea still in its infancy; it’s a vote of confidence in the clinician scientist’s skill and determination. Still, it’s impossible to know where the research will lead.

The grant provided critical support for developing a biomaterial called polypropylene fumarate (PPF) and testing its potential in orthopaedic applications. Today, Dr. Yaszemski and his colleagues at the Mayo Clinic College of Medicine in Rochester, Minn., continue to improve on PPF. They have extensively identified its properties and suitability for clinical use, and they’re creating composite materials based on PPF that may enable it to be used for a variety of orthopaedic applications.

Developing bone graft alternatives
The gold standard for bone graft material is autologous bone, which provides essential factors for healing. Its drawbacks include the limited supply of bone material and morbidity at the donor site. Alternative graft materials—allograft bone, metals, ceramics, and bone cement—have all been used successfully, but the limitations of each option provide an impetus for new strategies for bone reconstruction.

The alternative proposed by Dr. Yaszemski and his colleagues is an injectable, biodegradable material that might be inserted directly into a bone defect or a mold, or processed into a specific shape via solid, free-form fabrication to create a custom-fit graft for a specific defect or injury (Fig. 1).

The goal of their research is to meet the following design criteria:

• Biocompatibility. The material itself must be nontoxic, the conditions under which it solidifies and adheres to bone must be safe, and the byproducts of degradation must be nontoxic.
• Mechanical properties. The compressive modulus and strength of the material should be comparable to that of trabecular bone.
• Osteoconductivity and osteoinductivity. The material must provide a scaffold that enables the migration and proliferation of osteogenic cells. It must also deliver and release growth factors necessary to promote cell differentiation and bone formation.
• Degradable. The ideal material needs to degrade at a rate that is consistent with the development of new tissue, so that the mechanical function is transferred from the polymeric material to the new bone.
• Sterilizability. The material needs to be sterile at the time of injection. Also, the sterilization process itself must not alter other essential elements of the polymer, such as the mechanical properties or rate of degradation.
• Handling characteristics. The injectable material needs to flow into the defect, remain in place, and harden at a suitable rate for performing the surgical procedure.

Making progress
Dr. Yaszemski and his colleagues have developed PPF that meets these criteria in animal models of orthopaedic injury. With regard to the clinical application of this work, he recently reported, “It’s so hard to predict the future, but I think it’s reasonable that within about 5 years we’ll have a human use.

“I think we’re going to target holes in bone first,” he added, “such as vertebral compression fractures typical in women with osteoporosis. The treatment would be an alternative to polymethylmethacrylate bone cement.”

As his research team moves this strategy closer to clinical studies, they continue to refine the polymeric material in the lab. They are designing PPF composites with other polymers that may enable them to tweak the properties of the injectable material to suit a particular need. Other work focuses on properties of materials that may result in the controlled release of growth factors that reflect the complex sequence and concentrations found in normal bone growth and repair.

Recognizing progress
In recognition of Dr. Yaszemski’s work, the AAOS presented him with the 2009 Kappa Delta Elizabeth Winston Lanier Award. This award recognizes outstanding clinical research related to musculoskeletal disease or injury (Fig. 2).

Through department gifts made by the Mayo Clinic College of Medicine, Dr. Yaszemski is a longtime OREF Order of Merit contributor. Independently, through a major gift commitment given to OREF to support research in perpetuity, he is also a Shands Circle member. Dr. Yaszemski said that it behooves all clinicians to support orthopaedic research in some way.

“Anything we’re able to do for our patients today is a snapshot in time. Somebody worked on it—maybe a short time ago, maybe a long time ago—but we benefit from it. That process is continuous. We need to be working on things that will give better techniques to orthopaedists in the future. We can do this by using our treasure or our time and talent—or, for some folks, both.”

Jay D. Lenn is a contributing writer for OREF. He can be reached at communications@oref.org