Adam Jakus wasn’t too impressed with 3D printing at first.

While he found the process itself “neat,” Jakus was frustrated by the poor quality and limited quantity of available materials.

“My initial thoughts were ‘This is really neat, but the materials currently compatible with the system are terrible for biological/clinical applications and just terrible in general,’ and ‘these materials that do exist are a real pain to print,’” Jakus recalled during a 2021 3DHEALS interview. “As a materials engineer…I realized there was a major need and an opportunity to focus on developing new 3D printable materials of all kinds, not just biomaterials that were not only highly functional…but also very scalable, easy to implement, and infinitely versatile. That thought, combined with my prior five to six years’ research experience with creating structural thermites and other ‘energetic’ materials, made me realize there were endless opportunities before me…”

Jakus used those opportunities to disrupt the 3D printed materials market. Leveraging his knowledge of materials and tissue engineering, Jakus founded a company to refine and commercialize additive manufacturing (AM)-compatible biomaterials he developed working in a Northwestern University lab. His co-founder was Ramille Shah, Ph.D., an associate bioengineering professor who was equally as knowledgeable and experienced in biomaterial and tissue engineering.

Jakus and Dr. Shah’s Chicago-based company, Dimension Inx LLC, devises new substances through 3D painting, an advanced manufacturing technology that allows nearly any material to be 3D printed and fabricated into almost any form through simple, room-temperature extrusion.

3D painting uses particle-based inks comprised of 95% print material (metal dust, ceramics, organic tissue) and 5% medical quality biodegradable polymer. The technique allows for high loading of bioactive ingredients, rapid printing and drying at room temperature, and the elimination of processing techniques like cross-linking and sintering.

Due to their co-3D-printing compatibility, 3D paints are capable of producing multi-material structures. They also can be blended or mixed before or during printing to create substances with blended or gradient functionality that change over length or depth—a quality that makes it ideal for tissue and organ formation.

“…the 3D Paint and 3D Painting technology platform [is] a versatile means of designing and producing a near endless variety of 3D-printable materials,” Jakus, now head of his own advisory/consulting firm, noted to 3DHEALS. “It’s incredibly exciting to hand a new material, in 3D printed form, to a physician and see their excitement when they learn what it is and what it does—the number of ideas they generate…These professionals have been stuck with existing materials for so long, they didn’t realize certain things were not only possible but now available.”

Indeed, the possibilities realized by 3D painting have been notable, particularly regarding orthopedics. Jakus’s invention has introduced the industry to high-porosity materials; osteoinductive graphene; hyperelastic bone composite scaffolds; organ-specific decellularized extracellular matrices; and a regenerative bone graft.

The latter product, CMFlex, received U.S. Food and Drug Administration (FDA) clearance in December 2022 and made its clinical debut last fall. Designed to treat various oral and maxillofacial bony defects, CMFlex is comprised mainly of hydroxyapatite particles and biodegradable polylactide-co-glycolide polymer—materials that historically have demonstrated biocompatibility and clinical utility.

Dimension Inx combines these base materials into a proprietary, microstructurally porous composite substance called Hyperelastic Bone that is 3D printed into CMFlex. The easily deployable, customizable product is capable of absorbing fluid, which enables it to control bleeding during surgery while assisting the bone remodeling process once implanted.

“CMFlex is a product that represents our unique approach to restoring functionality in the body,” Dr. Shah, Dimension Inx’s co-founder and chief scientific officer/R&D head, said upon sharing news of CMFlex’s first clinical cases in October 2023. “CMFlex is…a dynamic collaboration between biology, material composition, microstructure, and macroarchitecture.”

Such collaboration has spawned numerous other material marvels within the orthopedic implant sector. Irish implant manufacturer Croom Medical, for example, is working with Pennsylvania-based Global Advanced Metals to develop the additive manufacturing capabilities of tantalum, a tough but malleable metal with proven biocompatibility, corrosion resistance, osteointegration, and high ductility.

Tantalum devices have demonstrated superior biointegration and reduced risk of toxicity, preventing bone resorption and mitigating stress shielding, which can lead to implant loosening.

Anika Therapeutics Inc.’s hyaluronic acid (HA) matrix Hyalofast is undergoing testing in the United States in preparation for eventual FDA approval. Described as a biodegradable resorbable, non-woven scaffold, Hyalofast is composed of HYAFF fibers, the company’s proprietary solid form of HA. The material is designed to entrap mesenchymal stem cells obtained from autologous bone marrow aspirate concentrate (BMAC) during chondral and osteochondral lesion repair. Hyalofast is implanted into a cartilage lesion with BMAC and fills the defect until it is eventually resorbed and replaced by new, hyaline-like cartilage that integrates with the surrounding tissues. Hyalofast helps repair chondral and osteochondral lesions without removing healthy subchondral bone.

Hyaluronic acid, tantalum, osteoinductive graphene, and bioceramics are just a handful of the alternative substances that may one day dethrone traditional orthopedic material stalwarts like stainless steel, titanium, cobalt-chrome, polyethylene, and poly(methyl methacrylate) (PMMA) bone cement. To gain a better understanding of material design and technological advancements in material composition, Orthopedic Design & Technology spoke to a handful of experts:

• James Hicks, application development engineer at Syensqo, a Solvay spinoff specializing in materials and chemical science. The company boasts more than 13,000 employees in 30 countries, and provides high-performance thermoplastic for implantable and medical devices/equipment. 
• Joan Maldonado and Jeff Ribley, district sales managers for Omniseal Solutions, a Saint-Gobain business specializing in high-performance polymer and metal sealing solutions.
• Stephen R. Smith, director of Market Development at Edge International, a Banner Industries company. Based in Warsaw, Ind., Edge International is a stocking distributor of medical-grade raw materials for implants and instruments used in the orthopedic, spine, and trauma sectors.
• Scott Taylor, chief technology officer at Poly-Med Inc., an Anderson, S.C.-based firm that designs, develops, and manufactures custom absorbable medical implants.

Michael Barbella: What trends are currently driving innovation in orthopedic implant materials?

James Hicks: The growth of ambulatory surgery centers (ASCs) is driving the need for efficiency in minimally invasive surgeries. These facilities do not have as much space or sterilization capabilities as large hospital facilities, therefore implantable devices and the instrumentation required for placing these devices efficiently is critical. Single procedure instrumentation often aids in these scenarios.

Sensor technology is also increasing in implants, allowing for additional monitoring of patient outcomes. Polymer materials offer a way to make patient sensing devices possible, as opposed to metal which could interfere with sensing technology.

Scott Taylor: Over the past several years, 3D printable materials including both metals and nonabsorbable plastics have driven significant innovation in orthopedics. 3D printing has unlocked lattice-based based porous designs, inaccessible to injection molding, that facilitate bone ingrowth into implantable orthopedic devices. These designs have been implemented in implants ranging from spinal fusion devices, to hip replacement joints, and craniofacial implants. More recently, PEEK and PEKK implants have been developed with similar characteristics.

To date, fully-absorbable materials with initial strength profiles similar to metal have not been realized. That could be changing, however, with advanced composite technology. For example, Ossio has released mineral fiber-reinforced products that approach the strength of bone. Bioretec has also launched fully absorbable fixation pins based on absorbable magnesium alloys. Recently, Bioretec received Breakthrough Device Designation for its fully absorbable RemeOs Spinal Interbody Cage.

Barbella: How does orthopedic implant design impact material choice?

Hicks: In load-bearing orthopedic applications, the mechanical properties of the materials used are critically important. The materials selected for large joint and spinal applications should have fatigue resistance, compression strength, and lubricity. Biocompatibility is also a critical requirement. Polymer materials, such as PEEK or carbon fiber-filled PEEK offer high strength and versatility in manufacturing either through machining or injection molding.

Taylor: Orthopedic implants require high-performance materials that exhibit tensile and compressive moduli sufficiently strong to withstand the forces experienced by our bones, tendons, and ligaments. The requirement for mechanical performance has to be balanced with minimizing the amount of foreign material implanted.

For bone-reinforcing implants, medical device designers have typically chosen titanium implants as their metal of choice due to its acceptable biocompatibility profile and wear resistance. More recently, engineers have begun using PEEK and PEKK as a high-performance synthetic plastic alternative to titanium, albeit with a weaker strength profile. Due to these strength differences, fully porous 3D-printed titanium implants that facilitate bone ingrowth have been more recently utilized in permanent implants, whereas implants with surface porosity are more common for PEEK medical devices.

For fully absorbable implants, products have most often used versions of poly(lactic-co-glycolic acid) (PLGA) material containing a high percentage of lactide to retain a sufficient amount of strength and stiffness for a sufficient amount of time (more than three months) without compromising biocompatibility, as has been the case with a number of 100% PLLA containing materials. In these cases, porous designs have been more slowly adopted, in part due to the weaker strength profile of absorbable polyester-based materials.

Orthopedic textile applications often incorporate UHMWPE fiber due to high strength and low stretch. Utilizing UHMWPE also allows for implants to be designed with less material to reinforce with an equal amount of load. These elements can be seen in orthopedic devices ranging from braided sutures to knitted or woven mesh constructs.

Many polymeric materials, however, suffer from creep behavior when used in orthopedic applications where the product experiences constant or cyclic loading. There is potential, and current momentum, in the development of composite structures that include at least a portion of absorbable material. Some composite structures specifically address the mechanical and creep behavior of polymeric devices, while some composites target specific biologic responses, e.g. the inclusion of β-TCP. Long-term, the inclusion of absorbable components can reduce the total mass of material at the implant site.

Barbella: What advancements in technology or manufacturing processes/techniques are impacting orthopedic implant materials? Has it resulted in new materials development?

Hicks: Additive manufacturing is a newer frontier for implants, especially structural implants such as cranial plates and spinal cages. Over the years, the implant industry has evolved from machined metal to machined polymer to printed metal, with the newest development being printed polymers. Syensqo has recognized these trends and has developed a new polyketone-based polymer for SLS-based 3D printing of implants.

Taylor: In the last five years, there have been many exciting developments in technology that will have a marked impact on absorbable medical devices. The real value of additive manufacturing is yet to be realized, and pioneering companies are just starting to make themselves known. Enabling technology for additive manufacturing includes artificial intelligence and iterative/generative design, with the promise to optimize product performance while minimizing the mass of implanted material.

Absorbable composites are a particular area of focus at Poly-Med, with high strength fiber-reinforced structures poised to provide significant advantages over traditional particulate-laden composites.
Surface modifications, involving physical changes to topography or chemical changes, are influencing biological responses with increasing predictability, meaning the advances that have been realized with metallic implant osseointegration can be increasingly translated to absorbable polymeric scaffolds.

Microelectronics and implantable sensors will also be incorporated for off-line or real time performance monitoring of implants for infection monitoring, osseointegration, and implant failure.

Barbella: What types of implant materials are most popular with orthopedic device manufacturers and why?

Hicks: In terms of polymers, PEEK has always been the most popular option due to its high strength and stiffness in structural, load-bearing applications. Additionally, the radiolucent properties of PEEK allow for easier visualization in medical X-ray, CT, and MRI imaging to facilitate post-operative diagnosis. Carbon fiber-filled PEEK also offers enhanced strength for these applications. Unlike implantable metal materials, implantable PEEK helps to minimize bone density reduction by continuing to simulate normal stress on surrounding bone tissue.

Stephen R. Smith: We continue to see demand for titanium and cobalt-chrome, the staple implant grades. They are tried and tested and FDA-approved. Some stainless for implants, primarily in Europe and also in developing countries. Current mill lead times, especially for cobalt-chrome, are very extended, so this may lead to more of a focus on titanium for any new product developments.

Taylor: Typically, most load bearing applications utilize either titanium as a metal option or PEEK or PEKK as high-performance nonabsorbable plastic options. In cases of absorbable or partially absorbable implants, most utilize a lactide-based polymer (e.g. PLLA or PLGA-based materials) due to the longevity of the material (>3 months strength retention), as well as stiffness at the time of implantation (1-2 GPa).

In textile-based application, many nonabsorbable implant will utilize a component of UHMWPE to ensure sufficient strength of the device is met. For absorbable products, most of our customers will utilize one of Poly-Med’s Lactoprene materials, which are block copolymers of lactide, trimethylene, and ɛ-caprolactone in some formulations. Poly-Med’s Lactoprene materials were designed to minimize the crystallite structure and size in the polymer throughout the manufacturing process and during degradation, degrading into historically safe byproducts in a predictable manner. This is of utmost concern given the historical challenges observed in 100% poly-lactide fibers. Composites based on polylactide are quite common, as well, particularly for molded articles. At Poly-Med, we use β-TCP, hydroxyapatite, and biphasic calcium phosphate specifically developed for solubility, biological response, and performance within Lactoprene matrices.

Product development fundamentally attempts to understand and minimize the risks associated with the target device, and there are plenty of risks that need to be addressed. This is compounded with the long and expensive developmental timelines of medical devices, and it is understandable teams want to avoid adding risk to projects by using existing materials. In most cases this makes sense but for many of the most innovative medical device targets, new materials are required. The relationship between the product development team and material suppliers is a key element to managing risks, whether it is a new material or one that has been on the market for decades.

Barbella: What are your customers most asking for/expect from in their orthopedic implant materials?

Hicks: The key material requirements we hear from customers looking for implant grade products are biocompatibility, regulatory support (FDA Master Access File information), and a robust library of technical information on the materials. Technical data often includes compatibility with different sterilization techniques as well as markability (laser marking).

Joan Maldonado: Our customers (which can encompass patients, surgeons, and healthcare institutions) depend on our company for protection and reliability that can be achieved through custom materials we use in our solutions for orthopedic devices and/or instrumentation. These materials provide the following benefits in improved patient outcomes and care:

• Faster Recovery Times: Materials such as biodegradable polymers and bioactive coatings can promote quicker healing and minimize post-surgical complications.
• Increased Functionality and Reduced Pain: Medical devices should restore mobility and alleviate pain effectively.
• Durability and Longevity: Patients want devices that last a long time, potentially eliminating the need for revision surgery. Material advancements in wear resistance and corrosion resistance are enabling this lifetime confidence.

Smith: As a distributor, our customers are primarily looking for us to have material readily available, or at least on shorter lead times than direct mill. The material has to be in full compliance with the approved specification in terms of chemistry, mechanical properties, size, and tolerance. The material has to come from manufacturers on the OEM’s approved melt source list, which generally means U.S. and European mills, although some consideration is being given to Asian sources, particularly if the implants are for the Asian market.

https://ajay.odt.rodmanadmin.com/contents/view_breaking-news/2024-03-18/fda-grants-breakthrough-device-designation-to-bioretecs-interbody-cage/ Most of Poly-Med’s customers request high-strength constructions that have longer lasting mechanical than required for most soft tissue applications. Again, most of Poly-Med’s orthopedic customers will select lactide-containing copolymer formulations due to relatively high Young’s modulus and long-lasting mechanical performance. For load-bearing applications, there is a desire for absorbable materials to reach the mechanical strength of bone, although this request has been challenging to meet with typical polyester-based formulations alone.

Barbella: What material challenges are introduced with 3D printing/additive manufacturing?

Hicks: As the additive manufacturing space for implantable materials continues to emerge, there are challenges with both FFF filament and SLS [selective laser sintering] powder printing. Parts created using filament materials often do not meet the demanding needs and high-quality requirements for orthopedic applications. On-demand filament printing also requires medical facilities to have on-site printing equipment and expertise.

SLS printing is a more viable option for orthopedic applications, though the capital equipment cost is high. SLS allows the creation of more complex geometries and better surface finish on finished parts. The recyclability of PEEK-based SLS has typically been a hurdle in the past, however, Syensqo’s implant-grade polyketone is highly suited for SLS printing with excellent recyclability of the powder.

Taylor: Additive manufacturing is continuing to impact orthopedic product development, and many 3D-printed implants have been cleared by FDA. The regulatory pathway is much clearer with guidance from FDA. However, there are significant material challenges that need to be addressed. Many 3D printing processes have the potential to leave voids within the product structure and these risks must be addressed through quality control, product design tolerances, sterilization, and other aspects of design controls. With absorbable materials, there just aren’t that many materials available for product design. Raw materials from Poly-Med or Evonik are among the few sources that can be used to design and manufacture additively manufactured devices, and there are fewer AM techniques available for absorbable polymers due to process-induced degradation risks. At Poly-Med, we are continually working to address material limitations through fundamental research and partnerships with external collaborators, from universities to startups to the largest medical OEMs.

Barbella: Is the EPA’s Final Rule on ethylene oxide (EtO) emissions going to have any impact on orthopedic implant material selection? Why or why not?

Hicks: From Syensqo’s perspective, our polymers are well-suited for multiple modes of sterilization, so we have not seen a significant impact on selection of our materials. We are continuously evaluating new, emerging sterilization processes to ensure we have information to provide our customers that need sterilization compatibility. As an example, newer techniques we have recently evaluated are chlorine dioxide and nitrogen dioxide.

Taylor: The EPA’s Final Rule may have an impact on selection of EtO as a sterilization method moving forward. To date, EtO is the most widely used sterilization technique for absorbable devices and exhibits the mildest effect on the mechanical properties and degradation time of absorbable materials. It may be challenging to change sterilization methods for absorbable medical devices already in the market because the sterilization process has a direct impact on product performance. Moving forward, e-beam and X-ray may be appropriate alternatives, although the impact on the degradation profile of the device must be assessed for appropriateness for the application. Alternative sterilization techniques, for example scCO2 and HPGP, may also be viable but must be tailored for any particular material.

Barbella: What regulations are impacting the selection of materials in the orthopedic segment?

Jeff Ribley: In any medical device, material biocompatibility remains critical. This is why regulatory and quality standard organizations such as USP [United States Pharmacopeia] and FDA work together to ensure biocompatibility and protect public health. Our business develops material solutions with custom materials; therefore, we understand our customers’ requirements, one of which is regulatory compliance. For example, certain “Codes of Federal Regulations” depict orthopedic devices and classifications thereof. A typical starting point is CFR Title 21 part 888, which addresses regulations and the like around ortho implants. All ortho companies use this as a guidance for future development projects all the way through 510(k) submittals.

As regulations continue to evolve and get more stringent, this will certainly impact material selection. On our end, we are helping customers with these challenges such as receiving USP Class VI certification. Materials that meet USP Class VI standards generally have a higher quality level of assurance and better acceptance with the FDA and USDA since materials should substantially lower the chance of patient injury—extremely desirable to manufacturers of orthopedic devices.