Becker's Spine Review

21 Executive Briefing: "The theory was that if the biomechanics were more consistent with bone there wouldn't be as many issues of subsidence, which is when the [implant] breaks into the bone being fused together," Dr. Bhatia said. Surgeons also gravitated toward PEEK's radiolucent characteristics. On an X-ray, the PEEK implants are hidden to the eye. This removes chunks of metal that often cloud X-rays when patients receive titanium implants. The radiolucent implants also allow surgeons to better evaluate whether the bone is healthy around the implant and if fusion was achieved. However, PEEK makes for an imperfect implant too. The predominant issue surgeons encounter with PEEK is bioinertness. The implants did not always heal to the bone, making it just a piece of plastic in the body, according to Dr. Bhatia. "PEEK is very bioinert, meaning nothing happens to it," he said. "In fact, if anything, the body creates a layer between the cage and the bone that the bone won't heal to." As a result, titanium implants reemerged. But researchers discovered a new issue with the substance. Multiple studies found titanium implants may release metal ions upon impaction that have adverse effects on bone cells, which could lead to implant failure and infection. One 2013 study published in the Clinical Cases in Mineral and Bone Metabolism provided an overview of the adverse effects of metal particles on bone cells and peri-implant bone Importance of the immune response It's long been known that the immune system plays a vital role in tissue healing. But only recently have experts come to understand the importance of the immune system in tissue remodeling and regeneration. In fact, researchers are now starting to better understand the different types of inflammatory responses that occur and the adaptability of immune cells. Stephen Badylak, DVM, MD, PhD, is Deputy Director of the McGowan Institute for Regenerative Medicine and is among the foremost experts in immune response and biomaterials. "What's become incontrovertible now is that the immune system plays an absolutely critical part in any biomaterial that's put in the body with respect to transplant outcome," Dr. Badylak said. Macrophages are our primary host defense, and their activation and response are based on the environment they are exposed to. In the initial stages of the immune response, macrophages will express an M1-like phenotype. The major function of M1 macrophages is to kill microbes through phagocytosis. The M1 cells produce proinflammatory cytokines and present antigens to T-cells in order to protect against foreign bodies, bacteria and viruses. "If one suffers a knife wound we would see a M1 pro- inflammatory phenotype in the surrounding tissue almost immediately. At day 4 or 5 we then see the expression of M2 pro-healing phenotypes. If a piece of the knife blade were to break off in the wound, we would see an extended M1 response which ultimately signals the body to wall-off the foreign body with fibrous granularized tissue". What researchers are now better understanding is that for healing to occur, "whether the affliction is a knife blade, a spinal implant or a cardiac stent, the proinflammatory M1 macrophage needs to convert or transition into the opposite M2 phenotype. The M2 macrophage cells are anti- inflammatory and promote healing" said Dr. Badylak. "Imagine having two materials and being able to make identical devices in terms of the mechanical properties, such as pore size, but one material promotes an inflammatory response (PEEK) and the other material (ZFUZE) promotes a remodeling response," Dr. Badylak explains. "With the inflammatory response, surgeons are going to get encapsulation or chronic inflammation around the implant whereas the remodeling response provides for the development of bone and that material incorporates the device into the bone that is being remodeled. These new biomaterials are not rapidly available in the market. "I think the only reason that you don't see these biomaterials is because it's such new information. We have tested over 300 different biomaterials with the M1/M2 Assay and have never seen immunomodulation like we have for ZFUZE in anything other than a natural molecule." n ZFUZE STUDIES • In Vitro Osteoblast Proliferation Assays – 700% increase • Rabbit Critical Defect Model – Increased Bone Mineralization Index • Ovine Cervical Fusion Model – Statistically Significant Reduction in Interleukin 1-beta • In Vitro Immunomodulation Studies – Positive M2 Immunomodulation DiFusion, Inc. is an advanced biomaterials manufacturer located in Austin Texas and has engineered multiple patented SMART Surgical Polymers. DiFusion was founded by Matthew Geck, MD of Austin Texas and Gary Ghiselli, MD of Denver Colorado. ZFUZE is currently pending FDA 510(k) clearance.

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