Becker's Spine Review

21 EXECUTIVE BRIEFING 2 EXECUTIVE BRIEFING SPONSORED BY The first new homogenous biomaterial for the spinal market in over 20 years W hile the number of spinal fusion procedures has increased dramatically over the last 20-plus years, the biomaterials from which spinal interbody fusion devices are manufactured have not changed substantially. Over this time, however, many significant drawbacks of these materials have been identified. A series of recent studies of a new "homogenous" biomaterial demonstrate exciting results, including that the new biomaterial avoids the pitfalls of other biomaterials. To learn more about the landscape for spinal biomaterials and the outlook for the future, Becker's Spine Review spoke to experts in the area of spinal biomaterials and reviewed the results of recent studies in this area. Issues with traditional spinal biomaterials Titanium and titanium alloys were the first biomaterials used for spinal procedures. But while these materials largely met the necessary mechanical requirements for spinal column support, drawbacks included modulus, chronic inflammation and a pro- inflammatory response of the immune system. Similarly, poly-ether-ether-ketone (PEEK), which became the dominant interbody used from roughly 2000 to 2018, has positive attributes including modulus equivalent to bone and good visualization. But PEEK has demonstrated poor osseointegration and elicits pro-inflammatory immune responses leading to less than desirable clinical results. Beyond titanium and PEEK, there has been little industry innovation in recent years. Derrick Johns, the CEO and founder of DiFusion Technologies — a company dedicated to engineering and bringing to market a suite of patented immunomodulatory, tissue regenerating and antimicrobial polymers — said, "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." In light of the current situation, the authors of a recent paper wrote, "There is need and opportunity to develop spinal implant materials that can provide the load-bearing function while simultaneously modulating a favorable immune response that mitigates inflammation and leads to effective osseointegration." DiFusion's ZFUZE ZFUZE™, developed by DiFusion Technologies, is a composite of PEEK (base material) and 14% 4A sodium aluminosilicate (zeolite), a super-hydrophylic ceramic material that carries a net negative charge and can also carry a wide range of absorbed ions that can promote healing. ZFUZE was developed to produce a material that was more bone-like and that would interact more favorably with tissues. ZFUZE is the first new FDA-cleared biomaterial backed by ISO 10993, which is a series of standards for evaluating the biocompatibility of medical devices to manage biological risk. The ZFUZE research and development process has involved lab, animal and human studies. These studies include: • Osteoimmunology testing i conducted by the McGowan Institute for Regenerative Medicine at the University of Pittsburgh. This testing found a decrease in chronic inflammation compared to titanium and PEEK and a 700 percent increase in osteoblast proliferation vs. 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, PhD, MD. • Animal studies ii by Boyle Cheng, PhD, 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 studies, iii led by Paul Kraemer, MD, of Indiana Spine Group, were conducted retrospectively with 44 patients. No patients were excluded, as is typically the case with 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. The results documented a 91.4 percent fusion rate at eight months. There was no endplate subsidence, no cage migration and no evidence of fibrous tissue encapsulation.

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