Magnesium implants and screws may be the compromise. They are mechanically robust when implanted, but dissolve in the body in a controlled manner that doesn’t cause tissue damage. Implants made of magnesium alloys are not only biocompatible, but their mechanical properties during the initial healing phase are bonelike. Magnesium implants could have a special impact on children whose bones are growing rapidly. The biodegradable screws don’t impair bone growth, saving the small patients a second surgery and consequently minimizing infection and cutting cost.
A resorbable screw’s blessing can also curse it, however. The dissolution is associated with complex corrosion processes that alter surface structure and yield a number of products. Depending on the type of magnesium alloy, hydrogen gas can develop due to insufficient corrosion resistance, even to the extent that a gas cushion is formed under the skin. If more hydrogen gas is formed than the body can remove, the healing process could be disrupted.
Researchers at the Swiss Federal Laboratories for Materials Science and Technology (Empa) are investigating magnesium screw bio-corrosion in realistic body conditions to find a solution. They hope to find the optimal magnesium alloys and other biocompatible elements, as well as new surface properties for resorbable magnesium screws, that don’t lead to gas pocket formation within the tissue.
“So far, it is already clear that the reaction is different depending on the level of acidity in the tissue,” explained Arie Bruinink, a researcher at Empa’s Laboratory for Joining Technologies and Corrosion.
Large amounts of hydrogen gas seem to form in a slightly acidic environment during magnesium corrosion. An alkaline pH range yields carbonate-containing products, which can inhibit magnesium degradation. In the pH value of blood—about a neutral 7.4—magnesium hydroxides and phosphate products are formed, which slow down further corrosion. But interstitial fluid, a thin layer of saline fluid surrounding the body’s cells, is the main environment of concern. A healing bone fracture is controlled by immune cells to produce a well-balanced structure of bone modeling and resorption, and the area is embedded in interstitial fluid. The acidity of this fluid varies much more widely than blood, so Bruinink developed experimental analysis techniques and flow cells to model pH regulation.
“The flow cell is a tiny lab that simulates the reality of bio-corrosion,” he explained. “As soon as it is clear what actually happens to the magnesium alloys during bio-corrosion, we will be able to produce suitable implants with functionalized surfaces that, for example, promote beneficial reactions of the biological environment.”
The rising incidence of fractures and other traumatic musculoskeletal conditions will only increase the demand for innovative trauma implants like magnesium screws. According to market research firm Global Market Insights Inc., the market will expand to $9.8 billion by 2025. As surgeons look to boost treatment outcomes, innovative solutions to orthopedic trauma repair present an area where orthopedic companies stand to capture a share of this market. Following are three companies that have developed novel technologies when accidents happen.
A Patient-Conforming Intramedullary Implant
Shortly following IlluminOss Medical's 2007 founding, the Providence Business News and The Rhode Island Economic Corporation named Robert Rabiner, then-president and CEO of the East Providence, R.I.-based company, the Rhode Island “Innovator of the Year.” The award recognizes entrepreneurs and organizations developing unique concepts, product solutions, and have shown outstanding forward-thinking approach.
“This comes at a very opportune time as we aggressively move forward with the development of our technology and the growth of our company,” Rabiner told the press. “We are honored to be recognized for what we believe is a very innovative approach to serving patients’ needs that we believe will provide an extremely important and viable treatment option for physicians who treat bone fractures of the hand, wrist, and forearm clavicle.”
The treatment option earning Rabiner and IlluminOss the award: minimally invasive, conforming orthopedic implants that leverage the company’s proprietary bone stabilization technology—the IlluminOss Photodynamic Bone Stabilization system. Composed of a Dacron balloon, a reusable biocompatible light-activated monomer, and a flexible catheter, the company touts the IlluminOss system as the world’s first patient-conforming intermedullary implant.
Intramedullary rods (also known as intramedullary nails or IM nails) have been used to treat long bone fractures for over 50 years. It works by forcing a metal rod into the bone’s medullary cavity, where it acts as a form of an internal splint to stabilize a long bone fracture with minimal damage to surrounding soft tissues. Today there are many types of intramedullary rods available, some made for specific fracture patterns. The IlluminOss system, however, customizes the approach.
“During a percutaneous procedure, a small diameter expandable balloon catheter is inserted into the medullary canal and is positioned across the area requiring stabilization,” explained Jeff Bailey, CEO of IlluminOss. “Once in correct alignment and position, it is infused with a biocompatible light curable liquid monomer that hardens under the application of visible (436 nm) light. Unlike traditional bone cements, the biocompatible monomer can be infused and aspirated, allowing infinite adjustment of the implant as it is only cured upon the activation of the IlluminOss visible light source, which rapidly polymerizes the monomer forming the implant. The cured implant conforms to the anatomic contours of the medullary canal, making it a customized intramedullary implant that stabilizes the fracture and provides immediate longitudinal strength and rotational stability to the affected bone.”
The IlluminOss system was granted its first regulatory clearance in the form of a CE mark in 2009. Two years later, a number of first clinical cases were achieved. Leading German trauma surgeon Dr. Thomas Gausepohl used the system to successfully treat a 91-year-old woman’s fractured ulna in June 2011. Dr. Gausepohl used it three weeks later to successfully repair and stabilize the fractured fibula of an 80-year-old woman. Ten days after that, another leading German trauma surgeon—Dr. Frank Hoffman—used the IlluminOss system to repair an 80-year-old woman’s distal radius fracture.
Following 2014 FDA approval of a trial using the IlluminOss system to treat humerus fractures due to metastatic carcinoma, the first two patients were treated using it in the U.S. for this condition. The system was used to treat a metastatic bone disease patient in its home state of Rhode Island two months later. It achieved FDA de novo clearance in December 2017 to treat impending and actual pathological fractures of the humerus, radius and ulna from metastatic bone disease. Clearance for traumatic and fragility fractures was received in August 2018, and the system was officially launched in the U.S. this past February.
“Unlike traditional metallic implants, IlluminOss provides several important distinctions,” said Bailey. “Once cured, the implant can be drilled and used in combination with ancillary hardware. Studies have shown the use of an IlluminOss implant provides an increase between three and five times in the pullout power of screws. This allows a surgeon to securely affix plates and screws in poor quality bone without a concern of screws loosening or backing out.”
“IlluminOss provides an exciting new option in fracture repair for difficult-to-treat osteoporotic or other patients with compromised bone, and is a much-needed addition to conventional treatment with nails, plates and screws,” Dr. Mark Goodman of the University of Pittsburgh Medical Center told the press when the IlluminOss system was launched. “The fact that this unique technology was designed specifically for use in patients with compromised bone enables surgeons to create a conforming implant for each individual patient and is a game-changer in fracture repair.”
According to the company, U.S. and European clinical efforts have demonstrated the IlluminOss system provides patient benefits such as small incisions minimizing soft tissue injury, short procedure times, reduced length of hospital stays, post-op pain reduction, and less use of post-op pain medications.
“In a recent presentation of patients treated with IlluminOss for distal radius fractures, 85 percent of patients resumed their normal activities of daily life (ADL) within two weeks of the procedure and 60 percent of patients resumed their normal ADL within one week of the procedure,” said Bailey. “Similarly reported was a reduction in the use of post-operative opioid pain medications. The minimally invasive approach and the stability provided by the implant allowed for significantly less use of post-operative pain medications. Management of post-operative pain was accomplished through the use of Paracetamol 4dd 1000mg, with only very infrequent use of a short-term dose of Tramadol. This as well as other studies have shown IlluminOss is a suitable method for the repair and stabilization of osteoporotic fractures in elderly patients.”
Repairing the Spine
Noblesville, Ind.-based Nexxt Spine’s headquarters sits two hours away from Warsaw, also known as the main orthopedic hub in the U.S. The company recently celebrated its 10-year anniversary—Oct. 20, 2009, marked the date a first patient underwent surgery from a prominent Nashville surgeon using a Nexxt Spine device. Since then, 600 surgeons worldwide have operated using products in the company’s portfolio. In 10 years, Nexxt Spine has grown from a boutique design and manufacturing company to a well-known name in the spine industry.
The company’s Matrixx line, launched in 2017, is a collection of 3D printed porous titanium interbodies. The implants feature optimized open architectural porosity, residue-free surface technology, and strong radiographic imaging performance. The implants are currently available in cervical, stand alone cervical, TLIF, TLIF oblique, and vertebral body replacement configurations. Nexxt Spine claims Matrixx has sold 20,700 units since inception two years ago. The company continues to invest in the field of additive manufacturing, with a recent purchase of six laser beam 3D printers.
The company’s Saxxony Posterior Cervical Thoracic System entered the U.S. market last December. Comprised of rods, pedicle screw and hook anchors, connectors, and set screws, Saxxony helps to immobilize and stabilize cervical (C1 to C7) and thoracic (T1 to T3) spinal segments as an adjunct to fusion. Among other conditions, Saxxony can be implanted in the event of traumatic spinal fractures and/or dislocations. All of the implant components are manufactured from titanium alloy (Ti-6Al-4V ELI), with some transition rods available to be manufactured from cobalt chromium.
Saxxony’s standard and smooth shank screws come in a variety of diameter and length combinations. Its low-profile cross connectors have multi-axis adjustability, and the system offers multiple configurations of offset, parallel, and axial connectors. Streamlined instrumentation also aims to ease rod placement and boost procedural efficiency.
“In terms of Saxxony, the real difference in our products are the ease of surgeon use,” said Andy Elsbury, president of Nexxt Spine. “Our in-house manufacturing coupled with strong surgeon relationships allows our team to design and iterate versions of products and tools that result in a cohesive system.”
The Stand Alone Cervical System released in August is the most recent addition to the company’s Matrixx product family. According to the company, surgeons have been using the system for cervical trauma patients. The standalone anterior cervical interbody fusion system, used as an adjunct to fusion at one or two contiguous levels (C2-T1) to treat degenerative disc disease in skeletally mature patients, is comprised of machined fixation screws and additively manufactured spacers.
“3D printing allows us to create a 7-micron surface roughness over the entire titanium implant rather than the endplates alone,” said Elsbury. “This surface technology—combined with varying pore sizes of 300, 500, and 700 microns that mimic bone—creates an amicable environment for bone ingrowth. We chose this implant design because of its combination of structured porosity and cellular relative surface texturing. This combination truly makes it a new foundation for growth. Mastery of bone biology relevance allows us to steer away from arbitrarily architectured pores and struts.”
Polyetheretherketone (PEEK) is a commonly requested material for spinal implants because of its biocompatible and inert properties, and due to the fact it has a high modulus and doesn’t deform under load over time. It is a widely accepted radiolucent alternative to metallic biomaterials in the spine community. However, using a PEEK implant for spinal fusion requires surface modification to promote bone ingrowth and can fail to provide clinically needed additional stability.
“Unlike the prior gold standard of PEEK implants, which can lead to fibrous encapsulation and poor osseointegration, we have created a system designed for fast and true fusion,” said Elsbury.
The Stand Alone Cervical System combines the functionality and benefits of a cervical interbody and anterior cervical plate. The implant is contained within the excised disc space and doesn’t protrude past the vertebral bodies’ mid-line edge, reducing soft tissue damage or irritation. The implants are also comprised of various heights and footprints for varying patient anatomies.
“Patients will also enjoy having less hardware in their bodies,” said Elsbury. “Stand alone cervical eliminates the need for a plate placed over their esophagus.”
Healing Bones with Ultrasound
Headquartered in Durham, N.C, Bioventus was formed in 2012 out of a joint venture between healthcare growth equity and venture capital firm Essex Woodlands and global medical technology firm Smith+Nephew. The company aims to provide solutions for active healing through orthobiologics and provide products that stimulate the body’s natural healing process.
The company’s surgical division consists of orthobiologics in the form of allograft, autologous, and synthetic bone graft offerings to assist in bone formation. The company also has a joint pain injection therapy portfolio. Finally, the Exogen ultrasound bone healing device—the focus here—stimulates the body’s natural healing process to help fractured bones mend.
Exogen is indicated for non-invasive treatment of established non-unions (when fracture sites show no visibly progressive signs of healing), excluding the skull and vertebra. It can also be used to accelerate the time to a healed fracture for fresh, closed, posteriorly displaced distal radius fractures and fresh, closed, or Grade I open tibial diaphysis fractures when they are managed by closed reduction and cast immobilization.
The device transmits low-intensity pulsed ultrasound (LIPUS) through skin and soft tissues. The ultrasound beam reaches a depth of more than 260 mm, its effective diameter is more than five cm, and the therapeutic span is 3.4 cm even after passing through 20 cm of soft tissue. LIPUS causes nanomotion at the fracture site. Cell surface molecules called Integrins, which convert mechanical energy to biochemical signaling within the cell, detect the nanomotion.
“The key molecule that is upregulated by the Exogen signal is cyclo-oxygenase 2 or COX-2,” explained Peter Shaw, chief medical officer of Bioventus. “The COX-2 enzyme is the regulating step in the production of prostaglandins (PGE), specifically PGE2. The PGE2 is released from the cell and is believed to upregulate a plethora of molecules related to fracture repair, such as bone morphogenetic proteins (BMPs), vascular endothelial growth factor (VEGF), alkaline phosphatase, and others.”
“Through this COX-2 action, Exogen exerts many positive effects of fracture repair; however, the two processes with the greatest effect are endochondral ossification and revascularization,” Shaw went on. “Through the action of molecules like VEGF, Exogen can enhance the process of angiogenesis (new blood vessel formation). It has been demonstrated Exogen can significantly increase new blood vessels invading the fracture site. These blood vessels carry nutrients and stem cells, which can elaborate a repair to the fracture. In endochondral ossification, the soft fracture callus is converted to hard callus by mineralization. Enhancing the process of mineralization closes the fracture gap, healing the fracture.”
Exogen transmits LIPUS to the fracture site through coupling gel, and the patient feels little or no sensation during the treatment. The treatment can be administered at home or work, for 20 minutes, or as prescribed by a physician. Patients are automatically alerted in cases of improper application or performance. Its treatment tracking calendar displays completed and missed treatment throughout the program (which, according to Bioventus, is 20 minutes a day, for a minimum of 120 days, with a 90 percent adherence to the treatment regimen) so physicians can easily verify compliance. According to the company, there are also no known contraindications for the Exogen device. On the contrary, patients with comorbid conditions have been found to receive the most benefit from the device because they are known to have the highest rates of complication and non-unions.
“Through its unique mechanism of action, we have discovered Exogen works best on the most comorbid conditions such as diabetes, advancing age, and smokers,” said Shaw. “However, this advantage is not only restricted to patients with compromised healing failing to heal their fracture, but also patients considered a high risk for surgery. This includes elderly patients at risk of delirium, or patients with dementia, extreme hypertension, extensive soft-tissue trauma, mechanical ventilation, metabolic acidosis, multiple organ failure, or coma. The ability to heal fractures without surgical intervention is a major benefit for this group of patients.”
Bioventus enrolled the first patients in its BONES (Bioventus Observational Non-interventional Exogen Studies) in September 2017. The studies will compare incidence of fracture non-unions in patients using Exogen vs. those receiving standard of care alone. The BONES studies will include long and small bones in both the upper and lower extremities.
“We are collaborating with the FDA to assess the effects of LIPUS on the heal rate of acute fractures in a variety of bones,” added Shaw. “This is an innovative direct-to-patient research study to assess heal rate (dichotomous outcome of healed vs. not healed/nonunion) of fresh fractures at risk of nonunion by LIPUS.”
Exogen also demonstrated the crucial feature of saving patients and healthcare systems cost.
“Recent guidance from NICE in the UK (MTG-12) showed that not only was the Exogen technology safe and effective, it also resulted in a cost savings of £2,407 over surgical methods of treating non-union fractures,” said Shaw.