Atlanta, Georgia - November 2007

Use of New Polymer May Lead to Longer-Lasting Artificial Joints Rob Kimball, Staff Writer, Medical Device Daily

The classic, some might say stereotypical, image of a hip replacement patient used to be an elderly person, hunched over in pain (picture a cane for added effect here), the new hip not working anywhere near that of the “original” equipment.

But one company, Active Implants (AIC; Memphis, Tennessee), says it is developing a new material that may be used to create longer-lasting implants, more resistance to deterioration and better able to fight off infection.

Researchers at the Campbell Clinic Department of Orthopaedic Surgery and the University of Tennessee Health Science Center (Memphis) presented a paper, sponsored by AIC, on use of a medical grade form of polyurethane polymer, used in other medical applications, at the recent combined meeting of the world’s Orthopaedic Research Societies in Honolulu. Their report touts the use of this polymer material for applications in joint reconstruction, with data indicating that it can reduce by seven times the harmful chemicals formed as a result of the presence of war particle debris in the body.

One avenue of research on this problem ahs been related to the reaction of implant materials to otherwise innocuous infectious agents.

And Richard Treharne, PhD, VP of orthopedic research for AIC, said that an “Ah-ha” moment put him on to this approach for reducing wear and infection, and a better pathway for understanding why artificial joints can react so differently in different individuals.

He said that researchers have long known that one of the first places that infections migrate to in the body is the joints. And he said that previous research at the Campbell Clinic found that even minute infections that do not cause any clinical symptoms – such as, for instance, those that enter the body during tooth brushing – can become attached to the wear particles of the traditional plastic material used in joint replacement, a type of polyethylene called UHMWPE, a plastic that articulates or rubs against an artificial hip implant.

What has been observed is that infectious agents such as these, once attached to wear particles, can create chemicals that destroy the bone around the hip joint by a process called “osteolysis.” This bone destruction can lead to implant loosening, which often leads to pain and an implant failure requiring major revision surgery.

“It’s a theory – not everyone believes it,” Treharne told MDD. But he thinks it’s more than speculation.

“I first heard about it a year and a half ago, and it was one of those ‘Ah-ha’ moments,” he said. “I started thinking about why could a replacement in one patient be fine 30 years later, and another replacement in a patient with similar demographics have bone loss and deterioration after just a few years.”

He said the next question was, “What were the variables?” An obvious variable, he said, is “an external element coming into the body. Our doctors on staff describe it as a ‘Trojan horse.’ A doctor can have complete sanitary conditions, and a sanitary implant. Then the patient gets with Trojan horse coming into the body through exposure to everyday, common infections.

“Our bodies handle these subclinical infections, but they end up going through the heart and to the joints – that’s why one becomes so sore when they have the flue or flu-like symptoms.”

He further explains, “These bugs (endotoxins) migrate to the joints of people who have hip replacement. If these endotoxins attach to those, they create compounds called cytokines, which are known to cause osteolysis. So the ‘Ah-ha’ theory is that one can have total sanitary conditions and still the hip material can be compromised with bacteria.”

This debris is well known to cause loosening of the hip implants, thereby limiting the useful life of these artificial joints.

AIC says its search for longer-lasting artificial hips is driven by the desire to be able to implant artificial joints in a pool of patients that seems to be getting younger – one of the emerging trends in orthopedics due to high-impact injuries among this group and the ability of new technologies to enable an early joint implant followed by a later revision, with greatly lessened risk of reduced mobility or adverse events.

Then there is the longer life expectancy for hip implant patients, and an increase in demand by patients for greater activity at all ages.

Treharne said that the name of the company reflects its true mission.

“Active Implants – we try to find something that will work in younger, more active patients. One of the main reasons surgeries are postponed or canceled is because there is a pretty high chance that they will get a revision – depending on who you ask or which part of the body” the implant is made.

“This family of products is already being used in some products in the cardiovascular and spinal area and are already on the market in various applications,” Treharne noted. “We’re hoping for an orthopedic total hip application. That may be the best place to work of all the products.

“There is about a 20-25% revision rate in the hips, so people postpone the surgery as long as possible. Unfortunately, these people stop doing what they want to do in life. When they finally take action – by then it’s kind of a race – you either die or you might be too late to retain any previous activities you are used to.“

UT’s Smith said, “Our laboratory has been studying the ear particles of the polyethylene material used in artificial joints for many years. This alternative material has produced results that warrant further research to confirm its superiority as a plastic implant material.”

“From an orthopedic surgeon’s perspective, I believe these findings are significant, and a signal that we may have entered a new era of joint replacement materials,” said Michael Lewis, MD, executive VP for medical development of AIC.

And Stephen Bradshaw, president/CEO of AIC, said that he research out of UT, “combined with other studies, confirms this family of polyurethane materials, used for years in cardiovascular applications, has properties equal to and now better than the traditional polyethylene used for joint replacement.”

 

Honolulu, HI - October 2007

Researchers Find Improved Polymer For Use in Hip Joint Reconstruction
Researchers in the Campbell Clinic Department of Orthopaedic Surgery at the University of Tennessee Health Science Center in Memphis, Tennessee, today presented a paper that indicates a new polymer under study for applications in joint reconstruction can significantly reduce up to seven times the harmful chemicals formed as a result of the presence of wear particle debris in the body. This debris is well-known to cause loosening of the hip implants and thereby limit the useful life of these commonly used artificial joints.

The paper, authored by Richard A. Smith, PhD, an assistant professor at UT Health Science Center, was presented today at the combined meeting of the world’s Orthopaedic Research Societies in Honolulu, Hawaii. The research was sponsored by Active Implants Corporation (AIC), a developer of pliable implant technology for orthopaedic applications.

A desire to implant artificial joints in younger patients, the prospect of a potential longer life expectancy for hip implant patients, and an increase in demand by patients for greater activity are all driving a search for longer-lasting artificial hips.

One avenue of research is related to the reaction of implant materials to infections. Researchers have widely recognized that one of the first places infections migrate in the body is the joints. Previous research by this group found that even minute infections that do not cause any clinical symptoms, such as those that enter the body during tooth brushing, can become attached to the wear particles of the traditional plastic material used in joint replacement, a special type of polyethylene called UHMWPE, a plastic that articulates or rubs against an artificial hip implant. Over the years, researchers have observed that once attached to the wear particles, infectious agents can create chemicals that destroy the bone around the hip joint by a process called “osteolysis”. This bone destruction can lead to implant loosening, which often leads to pain and an implant failure requiring major revision surgery.

Using particles of a special, medical grade form of polyurethane polymer, UT Health Science Center researchers found a significant reduction (up to seven times less) in the production of these harmful chemicals when exposed to infectious agents.

“Our laboratory has been studying the wear particles of the polyethylene material used in artificial joints for many years. This alternative material has produced results that warrant further research to confirm its superiority as a plastic implant material,” said Dr. Richard A. Smith, the UT Health Science Center researcher.

“From an orthopaedic surgeon’s perspective, I believe these findings are significant, and a signal that we may have entered a new era of joint replacement materials,” said Dr. Michael Lewis, executive vice president for Medical Development of AIC.

“The orthopaedic industry has been searching for over 40 years for a replacement of the traditional polyethylene used in hip replacement. Many have viewed this material as the weakest link in today’s total joint reconstructions. This groundbreaking research demonstrates we may have found not only a replacement, but an improved material,” said Robert Rylee, past president of Wright Medical Company and board member of Active Implants.

“This research, combined with other studies, confirms this family of polyurethane materials, used for years in cardiovascular applications, has properties equal to and now better than the traditional polyethylene used for joint replacement,” said Stephen Bradshaw president and chief executive officer of Active Implants Corporation. “AIC is a pioneer of advanced pliable structured material applications in orthopaedics and is pleased to contribute to the progress of a technology that will benefit patients around the world.”

Active Implants Corporation, a pioneer in pliable structured orthopaedic implant solutions based in Memphis, Tennessee, is preparing to commercialize their first polymer hip products with this new material in Europe by the end of this year. AIC, a new venture orthopaedic implant company is dedicated to developing pliable material implant solutions to benefit younger, more active patients. For more information visit www.activeimplants.com

As the flagship statewide academic health system, the University of Tennessee Health Science Center is focused on a four-tier mission of education, research, clinical care and public service, all in support of improving human health. Offering a broad range of postgraduate training opportunities, the main campus, which includes six colleges, is located in Memphis. For more information, visit www.utmem.edu

 

Memphis, TN - August 2007

Northwest Airlines World Traveler Magazine’s feature article “Spotlight on Memphis” included a section on the business future of Memphis’ biotech industry growth. The feature highlights Memphis with “cutting edge research, medical talent combined with logistic experience and distribution acumen.” While Memphis is home to several medical device “giants,” the article previewed the future and included Active Implants Corporation. From the special insert, “…the material has a similar elasticity as cartilage,” says Stephen Bradshaw, Active Implants President and CEO. By utilizing this technology, he notes, “We’re trying to extend the life of implant systems by having low–invasive technology and longer wear products.”

 

Memphis, TN - July 2007

Active Implants Corporation (AIC) announces the engagement of Haynes & Boone, LLP (HB) to manage the JOINT portion of its expanding intellectual property (IP) estate of novel pliable material technology. HB’s expertise in medical devices includes orthopaedic applications in the areas of spine and joint implants, instrumentation and surgical method. AIC’s work with HB will be limited to joint applications and ties directly with the company strategy to accelerate movement of its IP to issuance status worldwide. HB and their Medical Technology Practice Group have substantial experience with emerging and middle stage technology companies. “This aligns nicely with the stage and requirements of our company,” said President/CEO Stephen Bradshaw. AIC is developing a new generation of resilient implant solutions intended to provide earlier-in-life orthopaedic implant solutions that provide closer to normal results. The BioScience Group at HB has established a knowledge base particular to polymer chemistry that further aligns with the interests of AIC. The uniting of disruptive technology with developing domestic and foreign intellectual property portfolios provides protection, use and preservation of Active Implants’ product solutions. Specialized attorneys, technical knowledge and industry experience provide AIC with superb intellectual property guidance, prosecution and enforcement as it brings its products to the marketplace. The company will maintain their spine intellectual property portfolio with Kelley Drye and Warren.

 

Memphis, TN - February 2007

Following several years of research and development, Active Implants Corporation has successfully implanted their novel, artificial meniscus in sheep under the guidance of their orthopaedic medical advisory team and research staff in Netanya, Israel. The proprietary knee implant, produced from a proprietary polymer licensed by the company that has the same modulus of elasticity as cartilage and is biocompatible, is designed to replace the medial portion of the meniscus following a total menisectomy procedure. The meniscus is a pillow-like structure in the knee, resting between the femoral condyles and tibial plateau and serving several purposes that include absorbing shock impact to the knee and maintaining an articulation and lubrication regimen for the complex knee joint. Each year several million people damage their meniscus. Some heal without intervention and others can be repaired through existing arthroscopic procedures today. A portion of the meniscus injuries (or deteriorating conditions) require the removal of the total medial meniscus. An estimated 300,000 menisectomies occur each year. After the meniscus is removed there are limited options for that patient who will likely require total knee reconstruction surgery later in life. The company’s artificial meniscus in development is intended to provide these patients with an implant option that can replace the meniscus removed at time of removal. The AIC artificial meniscus is designed to restore the natural anatomy of the knee joint and the lubrication-articulation function, delaying and possibly eliminating the need for major surgery.

 

Memphis, TN - January 2007

Active Implants Corporation pioneers earlier-in-life orthopaedic implant solutions and defines a new market, Interventional Arthroplasty™. The company reports steady progress in the development of their innovative pliable implant solutions. Today people with degenerative joint conditions experience a gradual decline in joint function and increase in pain that can lead to major joint reconstructive surgeries. This gradual declining condition can take several decades. Many reach an advanced stage of joint degenerative and require major surgery and make up the patient base served in the Total Joint Arthroplasty market. These patients had limited treatment options over the decades of their declining quality of life. Treatments are primarily limited to physical therapy, pharmaceuticals and a change in life activities. Active Implants Corporation recognized an unmet need, to provide early stage implant options that restore quality of life earlier and that delay or eliminate the need for major surgery. Patients who could benefit from an earlier-in-life implant solution make up what the company has named the Interventional Arthroplasty™ market. This new market segment in orthopaedics can be compared to the Interventional Cardiology market that emerged over a decade ago with the advent of earlier-in-life, less invasive treatments of cardiovascular disease (angioplasty and stents) that reduced the need and associated costs and risks for major open heart surgery. The mission of Active Implants Corporation is to provide a new generation of implant solutions that restore the quality of life, earlier in life. The company expects to introduce an artificial knee meniscus as their first entry into the newly defined orthopaedics market of Interventional Arthroplasty™.