CRN Projects

Bioactive Nanofiber Matrix for Spinal Arthrodesis

Principal Investigators:
Erin L. Hsu
Wellington Hsu

Outcomes

The Cervical Spine Research Society (CSRS) awarded a $15,000 fellowship to Michael S. Nickoli, MD, for his project “A Synthetic, Heparin-binding Biodegradable Nanogel as a Stand-alone Biologic Substitute for Cervical Spinal Fusion.”  Dr. Nickoli will receive his award at the annual CSRS meeting in Los Angeles in December 2013.

In the United States alone, there are over 400,000 spinal fusion procedures performed annually to eliminate chronic pain from degenerative disc diseases. Spinal arthrodesis, which is a surgical procedure to fuse vertebrae, is performed to relieve back pain that cannot be managed by medication or other non-invasive treatments. Graft from a patient’s own bone as well as bone graft substitutes are commonly used in such procedures, but pseudarthrosis, or failure to fuse, continues to occur at unacceptable rates. These pseudarthrosis result in increased patient morbidity, the need for revision procedures, and a severe financial burden on the healthcare system.

Over the past decade, recombinant growth factors (that is, growth factors made in a laboratory) such as bone morphogenetic protein-2 (rhBMP-2) have been shown to increase the rates of successful fusion. However, recent controversy surrounding the safety of rhBMP-2 has led to an FDA warning against its use in the cervical spine, and many surgeons now avoid using this technology in the lumbar spine as well. This leaves a universally safe and efficacious bone graft substitute for spine fusion still to be identified.

Catalyst Project Principal Investigators Erin Hsu (left) and Wellington Hsu (center) with research team Sharath Bellary, MD; Chawon Yun, PhD; Kevin Sonn, MD; Sung Soo (Seth) Lee, PhD candidate in the Stupp group; and Michael S. Nickoli, MD.An interdisciplinary collaboration from materials science, chemistry, bioengineering, and orthopaedics is underway to design materials known as peptide amphiphiles (PAs) that self-assemble into nanofibers with bioactive amino acid sequences on the surface that are tailored to elicit a particular biologic effect. The goal of this CRN Catalyst Project is to develop PA nanofibers that bind to endogenous growth factors—those inside a patient’s own body—in an attempt to avoid the need for recombinant growth factors such as rhBMP-2 in successful spine fusion. One approach the Hsu research team has taken in collaboration with Samuel Stupp’s laboratory is to develop a PA nanogel that binds endogenous BMP-2 to localize the growth factor within the fusion bed site. Another approach they are investigating is the use of PA nanofibers that bind to glycosaminoglycans, which are cellular proteins that bind to BMP-2 and other growth factors that promote bone regeneration. Therefore, rather than binding BMP-2 directly, this PA nanogel system binds indirectly to numerous pro-osteogenic growth factors. With the development of these novel technologies by the Stupp Laboratory and their application and evaluation in an animal model of spinal arthrodesis by the Hsu Laboratory, the researchers have shown for the first time that spine fusion is possible without the use of recombinant growth factors. Their overarching goal in this collaborative effort is to develop a bone graft substitute for use in humans that is both universally safe and highly effective in achieving successful fusion.

Principal Investigators

Erin L. Hsu

Orthopaedic Surgery, Feinberg School of Medicine

Wellington Hsu

Orthopaedic Surgery, Feinberg School of Medicine

CRN catalyzes new research in regenerative medicine using nanotechnology strategies.