Spinal Biomaterial Demonstrates Early Healing in Retrospective Study

DiFusion Inc. is touting results of a study that validates the efficacy of ZFUZE, the first homogenous new biomaterial introduced in more than 20 years.

The ZFUZE retrospective study was conducted by Paul Kraemer, M.D., at the Indiana Spine Group and consisted of 41 patients who underwent TLIF [define] single and double level lumbar interbody fusions. Radiographic computed tomography (CT) analysis conducted by Medical Metrics Inc. on ZFUZE implants showed a 91.4% fusion rate at eight months. “Maybe the most important thing about the study was there were no exclusion criteria,” Kraemer said. “It included anyone who I felt had surgical pathology best amenable to a TLIF, which is my most common fusion technique. There were old people, patients with scoliosis and osteoporosis, lots of adjacent segment pathology and more. It’s a realistic view of a modern surgical practice—and the material acquitted itself very well. It fused and fused quickly. Importantly, it fused like we thought it would, with real bone seen on CT directly adjacent to the implant, including through the cage. Even better, there was no cage subsidence and no fibrous encapsulation. It’s a testament to the material acting in vivo exactly as we expected from our in-vitro and animal studies.”
 
Beyond titanium and PEEK, there has been little industry innovation in recent years, according to DiFusion Technologie Founder and CEO Derrick Johns. “ZFUZE overcomes the shortcomings of titanium and PEEK such as cage subsidence and fibrous tissue encapsulation. The industry has taken shortcuts with regard to new biomaterials. To date, they have merely applied surface coatings to PEEK and altered the surface topography of titanium. Large device companies are hesitant and may not be equipped to take on new biomaterial projects that take years to develop and test with no guarantee of success. ZFUZE is a long-overdue innovation,” he explained.
 
The ZFUZE research and development process has involved laboratory, animal and human studies. These studies include:

• Osteoimmunology testingⁱ conducted by the McGowan Institute for Regenerative Medicine at the University of Pittsburgh found a decrease in chronic inflammation compared to titanium and PEEK and a 700 percent increase in osteoblast proliferation versus titanium and PEEK. There was also pro-reparative immunomodulation, as ZFUZE increases Interleukin-10 and Interleukin-12. In addition, ZFUZE demonstrated higher levels of rhBMP upregulation versus titanium and PEEK. “We have tested over 300 materials here at McGowan and have never observed positive immunomodulation toward early healing like we see in ZFUZE,” said Stephen Badylak, M.D., DVM, Ph.D.
• Animal studiesⁱⁱ by Boyle Cheng, Ph.D., at Meadville, Pa.-based Alleghany University, using sheep and rabbits, found statistically significant reductions in proinflammatory cytokines Interleukin-1 beta and Interleukin-6 at six months versus titanium and PEEK, along with successful fusion.
• Human studiesⁱⁱⁱ led by Paul Kraemer, M.D., of Indiana Spine Group, were conducted retrospectively with 41 patients. No patients were excluded, as is typically the case in other retrospective studies; in fact, smokers, osteopenic and diabetic patients were all included. The average patient age was 67. Medical Metrics LLC performed third-party radiographic fusion analysis via CT scan for 91.4% fusion rates at an early eight-month timepoint.

“ZFUZE is truly an example of differentiated homogenous new material technology that bridges the gap between conventional PEEK and titanium. Specifically, ZFUZE shares the same advantages of standard PEEK relative to titanium in that it facilitates visualization of bone formation across the disc space, exhibits the same modulus of elasticity which reduces the risk of subsidence and does not produce metal wear debris,” noted Peter Whang, M.D., associate professor at Yale University in New Haven, Conn. “However, it is not associated with the formation of a fibrous capsule and promotes osseointegration, like titanium. There is ample data from basic science investigations, animal studies and now extensive clinical experience showing that this biomaterial does not give rise to chronic inflammatory changes which may limit the utility of PEEK and titanium. I am extremely excited about the potential of ZFUZE to bring about earlier and more robust bone formation for my fusion cases.”
 
By definition, biomaterials are foreign bodies. Historically, their design has largely been based upon mechanical and physical properties, and bio-inertness was a desirable characteristic. As the adaptability of immune cells and the role that biomaterials play on immune-mediated tissue responses become better understood, there is a shift toward designing materials that can proactively modulate the immune system.

Located in Austin, Texas, DiFusion was founded in 2009 and is dedicated to engineering and bringing to market a suite of patented Immunomodulatory, 

References 
ⁱ McGowan Institute for Regenerative Medicine – UPITT
ⁱⁱ Allegheny University – Center for Neuroscience: Un-plated Cervical Sheep Fusion Study Cage Study; DaVinci Labs: Rabbit Femur Critical Defect Study
ⁱⁱⁱ Indiana Spine Group and Medical Metrics LLC – Third Party Radiographic Fusion Analysis