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SQI: Simpson Querry Institute

Hsu, Stupp Labs aim to create bone graft substitute for spinal fusion

“If this approach works as we expect, we could create an off-the-shelf product that outperforms current autograft techniques at a fraction of the cost compared to state-of-the-art implants utilizing recombinant growth factor."


Mark McClendon, SQI Translational Research Officer

A research team based at the Simpson Querrey Institute (SQI) has been awarded a three-year, $300,000 grant from MTF Biologics to investigate a novel approach to spine fusion surgery that would avoid harvesting a patient’s own bone or delivering recombinant growth factors, both of which are associated with major drawbacks.

The investigators, led by SQI assistant director Erin Hsu and SQI director Samuel Stupp, will develop, characterize and test a composite scaffold made from human cadaveric bone (demineralized bone matrix, DBM) and a synthetic peptide amphiphile (PA) which forms nanofibers that specifically bind to bone morphogenetic protein-2 (BMP-2) — an extremely potent growth factor protein for bone regeneration.

DBM is created by acid-processing cadaveric bone, which removes the mineral component. Currently used by surgeons as a bone graft extender, it enables spine fusion operations to succeed with less bone taken from the patient, typically from a portion of the hip called the iliac crest. But Hsu and Stupp plan to develop a DBM-based material that doesn’t require any patient-derived bone graft harvest, which can lead to surgical complications and long-term pain at the harvest site.

Because DBM when used alone doesn’t promote sufficient bone regeneration for spine fusion, the researchers hope that adding the BMP-2-binding PA to the equation will address that problem.

“It makes a lot of sense to use this kind of PA for this approach because the PA is designed to specifically bind BMP-2, and BMP-2 is the most readily available and highly osteoinductive growth factor present in that DBM,” said Hsu, the principal investigator. “We’re trying to take something that’s a bone graft extender already (DBM) and turn it into a bone graft substitute so that you don’t need to harvest any bone graft from the patient. Instead of using the cadaveric bone plus the fresh, patient-derived bone, you could just use the cadaveric bone composite.”

If proven safe and effective, the new approach could have a major impact. Bone is the second-most transplanted tissue in the United States, with between 1.6 million and 2 million transplants performed each year. Approximately 500,000 of those procedures involve spine fusions.

The project requires combining the strengths of the Hsu and Stupp Laboratories. Erin Hsu and co-investigator Silvia Minardi are bone biologists, while Stupp and Mark McClendon, SQI’s translational research officer, bring expertise in characterizing nanomaterials, including the nanofiber scaffold with the PA that selectively binds to BMP-2. Wellington Hsu, a spine surgeon and Erin’s husband, provides a clinician’s perspective and experience in developing medical devices, and Stuart Stock is a specialist in bone imaging — which will be essential for analyzing the results of the research.

“We have put together at SQI the best possible interdisciplinary team to work on this important problem that will avoid clinical complications for the benefit of patients and extend the use of cutting-edge technology for bone regeneration,” Stupp said.

The team will perform 3D stem cell culture studies to estimate the regenerative potential of the materials under development. The best candidates will be tested and optimized for surgical handling properties, and then deployed in a rat model of spine fusion for studies investigating degradation rate, tissue fate and efficacy. The final product will be evaluated for both efficacy and bone quality outcomes in comparison to an existing FDA-approved product that utilizes recombinant BMP-2.

Hsu said the work could apply more broadly to bone regeneration in other areas of the body, such as bone defects in the extremities. It also could offer insight into how to encode bioactivity in bioengineered composite materials.

“If this approach works as we expect, we could create an off-the-shelf product that outperforms current autograft techniques at a fraction of the cost compared to state-of-the-art implants utilizing recombinant growth factor,” McClendon said.