Spinal fusion strategies advance toward clinical translation

One of the goals of the Center for Regenerative Nanomedicine (CRN) is to provide resources to scientists looking to translate their discoveries into real-world technologies. Leveraging these benefits, the laboratories of Samuel Stupp and Erin and Wellington Hsu performed important early stage research to demonstrate the potential utility of a synthetic peptide amphiphile (PA) nanofiber scaffold for spinal fusion.

The material — a PA which self-assembles into nanofibers that specifically bind to a growth factor protein that promotes bone regeneration (bone morphogenic protein-2, BMP-2) — has now garnered significant interest from industry partners who aim to eventually test its efficacy in human subjects.

The Stupp Lab designed and patented the PA nanofiber in 2003 and began studying its use in long bone healing, but the research took on exciting new directions after the Hsus joined the Simpson Querrey Institute (SQI) faculty in 2009.

The Hsus, both in the Department of Orthopaedic Surgery at the Feinberg School of Medicine, offered expertise in modifying the use of this material for spine fusion surgery. Erin Hsu is a bone biologist and her husband, Wellington Hsu, is a spine surgeon.

“Historically, bone is taken from a patient’s hip, broken up, and placed at the site of spinal fusion. However, this bone harvest can have unwanted consequences, such as long-term pain,” said Erin Hsu, the assistant director of SQI.

“Patients and surgeons want a product that would obviate the need for bone graft harvest from the hip, but currently available products are either insufficiently safe or effective. We are developing a bone graft substitute that uses PAs to both safely and effectively promote spine fusion.”

Aided by CRN funding, the laboratories collaborated on a study that showed the BMP-2-binding nanofibers could promote successful spinal fusion in rats while using 10-fold less recombinant human BMP-2 than existing clinical products. This was a key finding, because BMP-2 is an extremely potent growth factor protein for bone formation, but its use in high doses causes adverse side effects. The results of this study were published in 2015 in Advanced Healthcare Materials. 

Following this first publication, the researchers designed a form of this material with improved surgical handling properties, making it more feasible for eventual clinical use. The nanofiber material also tested favorably in rabbits in a comparative efficacy study co-funded by Medtronic, a company which has shown interest in a continuing partnership. Rabbits are commonly used to predict spinal fusion outcomes in humans, and the groups’ most recent work showed that this new version of the material works even better, reducing the need for recombinant growth factor by 100-fold.

The Hsu and Stupp labs are also exploring whether a composite scaffold made from human cadaveric bone and the synthetic BMP-2-binding PA can facilitate spinal fusion without the need for any recombinant growth factors. This effort was awarded a three-year, $300,000 grant from MTF Biologics in 2019 and represents another potential way to achieve spinal fusion while minimizing adverse side effects to patients. 

Erin Hsu said the second project — which involves modifying cadaveric bone, or demineralized bone matrix (DBM) — was made possible because of the flexibility offered by the CRN.

“The CRN funding gave us the ability to pursue related ideas,” Hsu said. “We took our developments in a slightly different direction and leveraged that CRN seed funding to obtain large-scale research support to pursue those ideas. DBM is used frequently in human spine surgery patients, but only in conjunction with other products or with autograft donor bone. We believe that this PA-DBM composite will work on its own, without the need to harvest the patient’s bone.”

The two laboratories have filed two patents related to this project, one on a newer iteration of the PA nanofibers and another on a nanofiber paste that can be form-fit into any implantation site. Discussions with the FDA are ongoing to advance this research toward clinical trials in humans. 

“This material is being designed for utilization in both open and minimally invasive procedures,” Erin Hsu said. “We believe this material is potentially transformative for the field of spine surgery, but it will also be useful in other orthopaedic procedures where bone healing is required.”