AMagining Future Possibilities in Orthobiologics

Kevin R. Stone, M.D., helped usher in the Age of Anabolics.
 
The San Francisco, Calif.-based orthopedic surgeon invented the world’s first orthopedic tissue regeneration template in 1986, giving hope to countless numbers of patients with torn knee cartilage. Debuting in 2000, Stone’s collagen meniscus implant (CMI) induces the body’s self- healing prowess to repair torn or missing segments of the knee’s main shock absorber. The implant is comprised of highly purified collagen, which acts as a trellis for new meniscus tissue growth.
 
Since gaining market admittance, Stone’s invention has helped repair more than 4,000 injured knees worldwide. Perhaps more importantly, though, it laid the groundwork for the cultivation of biological treatments for orthopedic injuries, a sector that was valued at $5 billion in 2015 and is expected to swell to $10.2 billion in 2025, according to Million Insights data. Driving this growth over the next seven years will be the planet’s aging population, technological advancements, changing (more active) lifestyles, and a steady increase in musculoskeletal-related conditions like arthritis and osteoporosis.
 
There will likely be no shortage of technologies available in 2025, as the orthobiologics field is already brimming with companies jockeying for market share. ODT’s January/February feature story “Biological Building Blocks” examines the trends and challenges shaping the orthobiologics market as well as some of the latest technologies available to patients. Michael Carter, general manager of Stryker Corp.’s Spine Division, was among the experts interviewed for the feature; his full input is provided in the following Q&A.
 
Michael Barbella: Please discuss the current trends in orthobiologics. What forces are driving these trends? Have they changed in recent years?
Michael Carter: Over the last year, the cellular allograft segment has continued to grow across the orthopedics space. Drivers haven’t changed in the last year, as there are continued pricing pressures, reimbursement challenges, low-barrier to entry in some regulatory categories, and vendor consolidation.
Another interesting trend is connected to the introduction of 3D-printed spinal implants, which are used with a variety of orthobiologics. For example, Stryker’s Tritanium In-Growth Technology, which uses additive manufacturing to build Tritanium cages, is designed to mimic the architecture of cancellous bone.¹ This unique porous structure is designed to create a favorable environment for cell attachment and proliferation,^2-3 and may be able to wick or retain fluid when compared to traditional titanium material.³ Supporting pre-clinical evidence suggests that there’s a biological and biomechanical interaction between the Tritanium in-growth technology and the boney environment.^2-6
 
Barbella: What opportunities does this sector present to companies that operate in this space?
Carter: The continuing trend away from recombinant growth factors is opening opportunities to meet surgeon needs and preferences with a variety of other options. These technologies include nonproprietary allograft chips, synthetics, demineralized bone matrix (DBM), and stem cell orthobiologics. Each has a different function or mechanism of action. Some act primarily as scaffolds, as in the case of allograft chips and synthetics, and others have signals that stimulate bone growth in the body, such as DBMs and stem cells.^7-8
There is a continuum of pricing for these products based on their characteristics and mechanism of action, which allows hospitals and surgeons to select the orthobiologics that meet their needs and budgets across a range of procedure types. In a highly fragmented marketplace where hospitals and surgery centers are looking for cost savings and a single vendor to supply all of their biologics requirements, Stryker is well positioned as a one-stop shop for customers’ biologics needs. The company offers a full portfolio of biologics products, including the No. 1 selling synthetic bone graft, Vitoss,⁹ a next-generation cellular allograft BIO₄; and a full range of allograft and xenograft tissue for trauma, sports medicine, and craniomaxillofacial procedures.
 
Barbella: What challenges/concerns are facing the orthobiologics industry? How can the industry and companies in this sector overcome these challenges?
Carter: A challenge for the industry in bringing orthobiologics products to market is that there are different levels of evidence and associated timelines needed for the various product indications. This, along with the need to offer a range of technologies to meet surgeon and hospital needs, requires significant long-term investment. Stryker’s Spine division has demonstrated its ongoing commitment to the orthobiologics space, building a broad portfolio of products and continuing to innovate. This includes a commitment to providing clinical data to support its products.
 
Barbella: Why is it so difficult/challenging to mimic the body’s natural biological healing process for bone?
Carter: It is challenging to mimic the body’s healing process for bone, as its function in providing support for the musculoskeletal system has to be balanced with the biology of bone regeneration.¹⁰ Bringing this balance of biomechanics and biology to life requires advanced manufacturing techniques that were previously unavailable.
Recent advancements in additive manufacturing, also know as 3D printing, have pushed beyond those limits and are driving innovation into previously unmanufacturable shapes that are designed to mimic the porosity of bone. For example, Stryker Spine’s portfolio of interbody cages is built with Tritanium technology, which is designed to mimic cancellous bone and was designed for bone in-growth and biological fixation.³
Since 2001, Stryker has invested in additive manufacturing and has collaborated with leading academic universities in Ireland and the U.K. to industrialize 3D printing for the healthcare industry. AMagine is Stryker’s proprietary approach to implant creation using additive manufacturing, which incorporates hundreds of quality checks per batch and enables Stryker to design and build Tritanium Cages with pinpoint precision, optimizing device characteristics, from pore size and porosity to shape and surgical features, for use in spinal surgery. The AMagine Institute, Stryker’s new global technology development hub located in Cork, Ireland, is the world’s largest additive manufacturing facility for orthopedic implants.¹
 
Barbella: What factors are currently driving innovation in orthobiologics?
Carter: Varying levels of evidence, and associated timelines are significant factors in innovation in orthobiologics. Stryker believes that the source of innovation lies in the long-term investments. Time will hopefully see new products be welcomed by the market in the near future.
 
Barbella: What interesting, new technologies are in the works?
Carter: 3D-printed spinal implants, which are used with a variety of orthobiologics and are built to mimic bone, remain one of the most interesting new technologies of the year. In particular, materials with fully interconnected randomized pore structures designed to mimic cancellous bone have been introduced to the market,⁶ which differs from other technologies with longitudinal channels and traverse windows that result in a uniform structure, as well as cages that offer porous technology that is only present on the surface. New technologies such as Stryker’s 3D-printed Tritanium are manufactured from a novel, highly porous titanium alloy material that was designed for bone in-growth and biological fixation.⁶
Another recent technology is the LITe BIO Delivery System, which Stryker launched in late 2016. The system simplifies graft delivery, accommodates a surgeon’s preferred graft materials, and allows for direct visualization of graft placement. The feedback from surgeons has been tremendous—the most appreciated features include the ease-of-use and the ability to clearly see where the bone graft material was being placed.
 
References
1. Data on file, Stryker’s Spine division
2. *RD0000053710: Tritanium cell infiltration and attachment experiment
3. *TREP0000053045 Tritanium Wicking Verification Test Report
4. *RD0000050927: Tritanium material capillary evaluation
5. SRL 15-02/Stryker-02-15
6. PROJ*43909: Tritanium Technology Claim Support
7. Walsh WR, Oliver R, Yu Y, et al., Demineralized Bone Matrix provides equivalent results to autograft in standard posterolateral fusion model in adult rabbits. AlloSource White Paper, 2012
8. BIB14-BR-4: BIO4 Technical Profile
9. Millennium Research Group: U.S. Markets for Orthopaedic Biomaterials 2014
10. Nouri A, Hodgson PD, Wen C. Biomimetic Porous Titanium Scaffolds for Orthopedic and Dental Applications. In: Mikerjee A, ed. Biomimetics Learning from Nature. Croatia: InTech; 2010.

*No correlation to human clinical outcomes has been demonstrated or established.