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Brad Estes, Ph.D., started out in medtech with Medtronic, where he witnessed firsthand the promise biologics had to revolutionize spine care.
“The R&D team expressed growing interest in incorporating biological elements into implant designs instead of relying solely on materials like stainless steel, polyethylene and titanium,” he said. “It was a turning point in my career when I recognized the potential of leveraging biology to enhance orthopedic solutions.”
Dr. Estes left Medtronic to earn a doctoral degree in biomedical engineering at Duke University. “That was my introduction to regenerative medicine and tissue engineering, and where I learned about the power of using cells, molecules and methodologies to regenerate various tissues throughout the body, with a specific focus on cartilage,” he said.
The lab where Dr. Estes worked at Duke used an emerging concept called functional tissue engineering, particularly in cartilage repair. “We were using fat-derived stem cells to generate cartilage and recognized that, while the tissue produced looked like cartilage, it didn’t have all of the function of cartilage,” Dr. Estes said. “We realized that we needed a cell and tissue scaffold that mimicked the functional properties of cartilage. That’s where the 3D woven structure came into play.
“The first papers out on the use of this structure for cartilage tissue engineering demonstrated two very important features,” Dr. Estes added. “One, it could be tuned to have the right mechanical properties to match cartilage and two, it could also support cell growth and tissue generation in the joint.”
His underlying engineering philosophy is that transferring the functionality of an orthopedic implant to native tissue is required for success. “Implants will always eventually fail if they don’t integrate and remain integrated with surrounding tissue,” Dr. Estes said.
That fundamental truth inspired the innovative hip implant he helped develop at CytexOrtho, where he’s Co-Founder and CEO. “The implant serves as a foundation for regenerating cartilaginous tissue while seamlessly integrating with the body,” Dr. Estes said. “It’s a medical device because it’s an implant that re-establishes the form and function of the joint. It’s also a regenerative medicine play because it supports tissue regeneration and is ultimately completely replaced by newly generated tissues.”
Dr. Estes and his team combined two distinct structures to make their implant: a 3D-woven textile on one side of the implant that mimics the toughness, flexibility and compression properties of cartilage and a 3D-printed structure that is attached to the textile portion to facilitate anchorage into the bone. The textile is engineered to replicate the mechanical properties of articular cartilage and serves as the cartilage layer of the implant. The bottom printed layers are designed to seamlessly anchor into and integrate with existing bone tissue and facilitate new bone formation, making them highly osteoconductive. After 24 months, the implant completely dissolves, leaving behind natural tissue.
The implant has shown promising results in various animal models. “Even as the implant has experienced measurable degradation and absorption, we’ve observed that the joint’s restored anatomy is maintained at one year and provides continued joint functionality,” Dr. Estes said. “From biomechanical and biological perspectives, there’s no reason why the joint wouldn’t sustain its normal functioning, especially since there are low levels of inflammation and the remaining implant is completely encased within healthy tissue.”
In a one-year canine study, the implant displayed solid integration with native tissue and maintained joint contour. The treated animals regained normal gait and activity levels within three months. CytexOrtho is set to begin the product’s first human trial this summer. It will involve 15 patients to primarily assess safety but also to begin to assess the effectiveness of the device’s ability to restore a patient’s routine activity and to integrate with native tissues.
About a million individuals in the U.S. under the age of 65 suffer from hip osteoarthritis. Physical therapy is commonly prescribed and is sometimes followed by corticosteroid injections, despite their controversial nature and potential to cause long-term damage to cartilage. Patients who still suffer from chronic pain might also receive hyaluronic acid injections.
Tad Vail, M.D., who recently stepped down as Chair of the Department of Orthopaedic Surgery at UCSF and serves on CytexOrtho’s clinical advisory board, has been a key advocate for the development of the company’s implant. “He explained to us that providing even just five additional years of pain relief would be a significant victory for hip OA patients, given the immense impact that chronic disability has on their lives,” Dr. Estes said.
CytexOrtho is currently the only company addressing OA in the hip.
“The younger patients who suffer from severe hip pain represent a significant market opportunity,” Dr. Estes said. “Their need for better solutions compels us to shift to earlier treatment in their care continuum. Our implant could be the only solution these patients need. But even if future treatment is needed, all options would still be available — whether it’s another CytexOrtho implant or a total hip replacement later in life, which would be better indicated when they’re less active.”
Filling in the Cracks
SurGenTec’s OsteoFlo NanoPutty received FDA 510(k) clearance in 2020. For Travis Greenhalgh, the company’s Founder and CEO, the achievement marked his success in developing a compound with diverse phases that mirror bone remodeling and reaffirmed his efforts to create unique regenerative solutions in the me-too orthopedic and spine markets.
“I’m committed to innovation and differentiation and steering away from imitation,” Greenhalgh said. “It’s crucial to offer solutions to longstanding problems and enhance surgical outcomes by making procedures better, faster, more efficient and less invasive.”
During the development of OsteoFlo NanoPutty, Greenhalgh set out to create a quadriphasic technology that combines phosphate, beta-tricalcium phosphate and hydroxyapatite in one particle to gradually release and replace bone over time. Additionally, the putty’s nano-surface technology promotes bone growth and osteocyte attachment. Greenhalgh said the product has been on the market for nearly four years and has performed well due to its hydrophilic nature.
Last March, SurGenTec announced FDA 510(k) clearance and the first implantations of OsteoFlo HydroPutty. The synthetic dry formulation features a unique carrier that absorbs blood, bone marrow aspirate or saline, forming a cohesive putty that integrates well with autografts during surgery. It can be applied during a wide variety of spine and orthopedic procedures in contained spaces, fractures and voids to promote bone healing.
“The particle was modified to carbonated apatite, which closely resembles human bone. Preclinical testing demonstrated significant bone growth,” he said. “Muscle pouch studies showed that the particle effectively recruits stem cells, and surgeons have been impressed with the results.”
Greenhalgh teased a new version of the OsteoFlo NanoPutty, which should hit the market later this year, and said the product will be unique within the bone graft industry. The soon-to-be-released product has undergone studies at Florida International University that demonstrated a significant increase in stem cell yield compared to existing delivery methods.
Greenhalgh said conventional synthetic materials involve the use of granules that act like loose sand or gravel, making it difficult to retain their positioning within bone voids. Various carriers have been developed to create a cohesive matrix that resembles putties. However, Greenhalgh noted that the carrier material in these putties tends to resorb quickly, leaving the particles loose and scattered and resulting in a lack of sustained containment and efficacy over time.
“HydroPutty offers a unique solution by maintaining cohesion and integrity over an extended period,” he said. “Unlike most other synthetics on the market, it retains its containment even when immersed in water for hours or days. This feature is crucial as it ensures that the graft remains in place post-surgery, facilitating the arrival and activity of stem cells at the desired healing site.”
Greenhalgh said many physicians are dissatisfied with conventional bone graft delivery methods, such as bone marrow aspirate needles that are difficult to use and result in a low yield. He also pointed out that synthetic materials often comprise larger particles that clog or jam standard delivery systems, frustrating surgeons as they fill disc spaces or fracture sites.
SurGenTec’s products address these concerns by passing through extremely small apertures — as small as 2mm in diameter. This level of precision engineering is essential, Greenhalgh said, considering SurGenTec’s particles typically measure between 0.3 and 1 micron.
This size is significant, as it directly impacts the applicability of the products in various delivery systems, Greenhalgh said.
“The advantage of our products lies in their ability to reach and fill the tiniest of spaces, such as cracks, crevices and fracture sites,” he added. “This capability is invaluable in minimizing incision sizes and facilitating access to confined surgical areas without the risk of aperture obstruction.”
Common misconceptions about the current quality of synthetic bone grafts lead to skepticism about their efficacy, according to Greenhalgh. “The initial generation was introduced 15 to 20 years ago and faced limited regulatory scrutiny compared to current standards,” he said. “Consequently, their performance fell short, which contributed to doubts about the effectiveness of synthetic grafts.”
He pointed out that significant strides have been made in the field, driven by advancements in research and development across various companies. These innovations have elevated synthetic bone grafts to a new level, characterized by improved efficacy and features such as resorption surface technology.
Despite these advancements, Greenhalgh said, outdated products remain in hospital contracts and group purchasing organizations, hindering the adoption of newer, superior alternatives. “Patients don’t have access to the best possible care,” he added.
The advantages of new synthetic grafts extend beyond efficacy. “Unlike allografts, which are subject to variability and potential contamination, synthetics offer consistency and reliability,” Greenhalgh said. “Each batch undergoes rigorous testing and adheres to a standardized recipe, ensuring uniformity across all applications. In contrast, allografts present uncertainties regarding donor characteristics and formulation changes, posing risks to patient outcomes.”
Synthetic bone grafts have undergone a significant evolution, driven by years of research, scientific expertise and regulatory scrutiny. “It’s an exciting time for the industry as it continues to push boundaries and offer innovative solutions to address longstanding challenges in orthopedic and spinal surgeries,” Greenhalgh said.
Reinforcing Repairs
Anika Therapeutics is staking its claim in the regenerative medicine space with a proprietary biodegradable, non-woven scaffold comprising HYAFF, a benzyl ester of hyaluronic acid, that supports the entrapment of mesenchymal stem cells for the repair of chondral and osteochondral lesions.
The knitted version of the technology is included in the company’s Integrity Implant System, a porous, flexible construct knitted with HYAFF fibers that are designed to support cell infiltration and regenerative healing after rotator cuff repair. HYAFF resorbs over time as tissue remodels.
Anika identified an unmet need in the market related to the inherent weakness of some biologic products. “Collagen, for instance, tends to lose its strength when it gets wet, making it challenging to manipulate during procedures and susceptible to tearing upon fixation,” said Cheryl Blanchard, Ph.D., Anika’s CEO. “To address this challenge, we focused not only on the regenerative properties of our product, leveraging our expertise in cartilage repair with high HYAFF technology, but also on enhancing its strength.”
Anika combined HYAFF technology with polyethylene terephthalate, a polymer resin that’s commonly used in sutures.
“That allowed us to develop a construct with remarkable strength, high suture retention and tear resistance,” Dr. Blanchard said. “Surgeons have told us that it’s easy to manipulate and place arthroscopically, particularly during shoulder procedures.”
Integrity is also showing promise in other applications, including limited releases for the repair of Achilles and patellar tendons and in foot and ankle surgery.
Anika is focused on expanding its product portfolio in the regenerative medicine space. “Integrity is a versatile platform technology that can be further leveraged across various applications,” Blanchard said. “We’ve established a regulatory pathway that will enable us to innovate rapidly.”
Anika’s regenerative medicine portfolio also includes Tactoset, a synthetic injectable and settable bone void filler primarily used for treating insufficiency fractures. The company has received a special claim that permits the use of Tactoset to augment hardware, including suture anchors like Anika’s XTwist, to enhance their retention strength in low-quality bone. Tactoset is primarily applied in the shoulder, but is also being used in foot and ankle procedures.
“We’re focused on building out our regenerative portfolio in a market we have a real right to win,” Dr. Blanchard said.
