BETTER BODIES with BIOMATERIALS: How Ceramic and Glass Contribute to the $110B Global Market for Implantable Biomaterials

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BETTER BODIES WITH BIOMATERIALS: How ceramic and glass contribute to the $110B global market for implantable biomaterials

By April Gocha and Lisa McDonald

Ceramic and glass biomaterials integrate with the human body in diverse ways to support human health. As aging populations and evolving healthcare approaches shift the medical landscape, increasing opportunities for both established and innovative technologies predict a strong future for ceramics and glass.

here are few systems that can Tefficiently incorporate materials that provide structural support, filtration capacity, energy generation, energy storage, electrical conductivity, gas exchange, processing power, dynamic flexibility, and regenerative potential into one integrated, highly functional, and incredibly adaptable self-contained system. Yet the human body is a system that can provide all those functions and many more, and it does so through a unique collection of highly functional materials.

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Collectively those materials enable everything our bodies do, and they often retain functionality throughout the human lifespan, which worldwide is an average of 73.2 years.1 However, the materials are not always perfect and sometimes fail due to overuse, injury, disease, or genetics—circumstances that are becoming Bone more common as worldwide populations Orthopedic hardware age due to population dynamics and Porous scaffolds for repair increasing life expectancies. Eye Bone grafts, fillers, cements Globally, the number of individu- Corneal implants als over 65 years old surpassed that of Orbital implants children under 5 years old for the first Ear time in history in 2018. And while an Retinal implants Middle ear implants— estimated one in 11 individuals (9%) ossicular prosthesis, around the world were over 65 years old piezoceramic crystals in 2019, the older population is expected Cochlear implants to increase to one in six (16%) by 2050.2 These trends affect nearly every aspect of life, perhaps most notably healthcare. Teeth Jaw Individuals are living longer and are Craniofacial reconstruction Prosthetics, implants, veneers, remaining active until later years of life, Dental implants demanding enhanced strategies to main- dental cements tain longer functionality of the body’s materials. Humans have long turned to bioma- Spine terials in diverse forms to repair, replace, Spinal implants and fusion devices or enhance bodily materials (Figure 1), Skin Bearing surfaces for disc replacements establishing a global market for implant- Wound healing Implantable pulse generator devices able biomaterials that was estimated to Tissue regeneration be worth nearly $110 billion in 2019.3 While metals, polymers, ceramics, and glass all are used for biomaterial applications, ceramics and glass have a par- Heart ticular advantage, says Frank Anderson, Hip, knee, shoulder joints Cardiac pacemakers, defibrillators vice president of Global Research and Valves and seals on heart pump Joint implant articulation surfaces, Development at CoorsTek (Golden, ventricle assist devices Colo.). “Many technical ceramics are coatings at bone interfaces inherently biocompatible, chemically- resistant, and inert, which gives them a unique advantage over other implantable materials,” he says. Internal space The global market for bioceramics Various components, sealings, was valued at $14.5 billion in 2016 and packaging for implantable devices is predicted to reach a value of $20.2 Implantable sensors billion by 2021, growing at a 6.9% com- pound annual growth rate (CAGR).4 The market is mainly dominated by alumina and zirconia, which account for 75% of the market due to primary use of these materials in bone and dental implants. Other bioceramics frequently Figure 1. Ceramics and glass help found in implantable devices include repair, replace, and enhance all hydroxyapatite and tricalcium phos- types of bodily materials. phate, and bioactive glass also has clini-

18 www.ceramics.org | American Ceramic Society Bulletin, Vol. 99, No. 9 cal applications with rapidly expanding potential throughout the human body. It should be noted that while these materials predominate many implantable applications within the human body, mainly due to their acceptance and time on the market, other ceramic and glass Bone compositions are also suitable for many of Orthopedic hardware these applications, and we might expect Porous scaffolds for repair their purview to expand in future markets. Eye Bone grafts, fillers, cements Collectively, ceramic and glass materials Corneal implants enable many different kinds of implantable medical products that not only Orbital implants Ear significantly contribute to human health Retinal implants Middle ear implants— but also constitute robust industries with ossicular prosthesis, rich economic impact. Table 1 provides piezoceramic crystals a sample of some companies that manufacture ceramic and glass biomaterials or Cochlear implants implantable products. The following sections highlight a Teeth Jaw handful of applications for ceramics and Craniofacial reconstruction glass in the human body. Although the Prosthetics, implants, veneers, Dental implants listed applications are not exhaustive, the dental cements diversity highlighted here should provide a flavor of the vast potential of ceramics Spine and glass within the human body. Spinal implants and fusion devices PACKAGING: GLASS PROTECTS BOTH Skin Bearing surfaces for disc replacements BODY AND DEVICE Wound healing Implantable pulse generator devices Ceramic and glass materials are incor- Tissue regeneration porated into or play supporting roles in many electronic devices implanted into the human body, such as neurostimula- tors and pacemakers. In these applica- Heart tions, a bioinert and long-lasting barrier Hip, knee, shoulder joints Cardiac pacemakers, defibrillators between the device components and the Valves and seals on heart pump harsh environment of the body is imper- Joint implant articulation surfaces, ventricle assist devices ative to protect both—precisely a job for coatings at bone interfaces ceramics and glass. For instance, glass-sealed feedthroughs and packaging often encase the batteries for implantable pacemakers, where a Internal space hermetic seal preserves both function of Various components, sealings, the device and safety of the patient. packaging for implantable devices “Glass is used to seal the terminals of Implantable sensors pacemaker batteries. It acts as an electrical insulation material for the metal conductors. At the same time, glass creates a reli- ably gas-tight barrier when hermetically sealed with the electrical contact pins,” says Jochen Herzberg, medical program manager of Schott’s Electronic Packaging business unit (Landshut, Germany). “Specially selected glass types are resistant to the highly corrosive environment in the battery. And it doesn’t deteriorate

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or get brittle over time like polymers or nique provides a hermetic seal for bat- glass package, this is possible by stacking epoxies. It enables a higher reliability and tery feedthroughs, there is another glass base wafers with spacer glass and cover a longer device lifetime.” technology that comes into play when or etched lid wafers, thereby creating a To manufacture the glass-to-metal miniaturization or encapsulation of cavity in which the sensor device will sealed packages and feedthroughs, heat-sensitive components is required. be encapsulated,” Herzberg says. “The Schott presses finely ground glass For those applications, Schott has stacked glass wafers are then laser-sealed, powder into a ring shape that is then another solution with its Primoceler resulting in a gas-tight all-glass sen- sintered and assembled with the metal glass micro-bonding technology. This sor package. One major advantage of conductors inserted in the middle of wafer-scale technology uses a laser to Primoceler laser bonding technology is the ring and an outer metal casing. The precisely and locally bond glass to glass, that it all happens at room temperature. three components then undergo a seal- creating a vacuum-tight bond with no So even if the sensor is very heat sensi- ing process in a belt furnace to bond the additional materials. tive, which is usually the case, it can be materials together. “If you want to encapsulate, for packaged using the Schott Primoceler Although this manufacturing tech- example, a miniature sensor inside of a process. The extremely precise laser fuses

Table 1. Select companies that manufacture ceramic and glass implantable medical products or components* Company (location) Annual revenue (millions)* Website Role in value chain

Johnson & Johnson $82,100 www.jnj.com Develops, manufactures, and supplies diverse healthcare products, including medical devices such as orthopedic products Stryker $14,900 www.stryker.com Develops, manufactures, and supplies diverse healthcare products, including medical devices such as orthopedic products Kyocera Corp. (Kyoto, Japan) $15,404 http://global.kyocera.com Develops, manufactures, and supplies advanced materials to diverse •Life & Environment Group, business $760 markets; medical application is mainly ceramic hip implants segment that includes medical and healthcare Zimmer Biomet (Warsaw, Ind.) $7,982 www.biomet.com Develops, manufactures, and supplies orthopedic products, including artificial joints and dental prostheses Schott AG (Mainz, Germany) $2,568 www.schott.com Develops and manufactures diverse glass and ceramic products, including dental materials, medical device electronic components, implant packaging The Straumann Group (Basel, Switzerland) $1,746 www.straumann.com Develops and manufactures diverse dental solutions, including implants, prostheses, technologies, and biomaterials Morgan Advanced Materials Plc $1,356 www.morganadvancedmaterials.com Develops and manufactures ceramic components for medical (Windsor, U.K.) applications, such as feedthroughs for implantable devices Wright Medical Group NV (Middlesex, U.K.) $921 www.wright.com Medical device, especially orthopedic surgical solutions and biologics CoorsTek (Golden, Colo.) $1,000‡ www.coorstek.com Develops and manufactures technical ceramics for numerous industries, including orthopedic and implantable ceramics, (including ceramic hip implants), medical device components, and pharmaceutical components. Ceramtec Gmbh (Plochingen, Germany) $727 www.ceramtec.com Develops and manufactures ceramic orthopedic components (including •Medical products $304 ceramic hip implants), dental implants, and medical engineering devices Nobel Biocare (Zürich, Switzerland) $629‡ www.nobelbiocare.com Manufactures and supplies diverse dental solutions, including implants, prostheses, technologies, and biomaterials Rauschert GmbH (Pressig, Germany) $67‡ www.rauschert.com Manufacturer of technical ceramics, including ceramic medical components DSM Biomedical (Exton, Pa.) $65‡ www.dsm.com/biomedical Develops and manufactures biomaterials including bioceramics for diverse healthcare industries Collagen Matrix Inc. (Oakland, N.J.) $15‡ www.collagenmatrix.coc Manufactures collagen and mineral-based medical products for dental and orthopedic applications, including ceramic and bioglass bone grafts Mo-Sci (Rolla, Mo.) $6‡ www.mo-sci.com Develops and manufactures high-tech glass, including bioactive glass for medical applications Lithoz GmbH (Vienna, Austria) $5‡ www.lithoz.com Develops and manufactures additive manufacturing technologies, particularly with ceramic materials, for diverse industries including medical applications CAM Bioceramics (Leiden, The Netherlands) $3.5‡ www.cambioceramics.cco Develops and manufactures calcium phosphate biomaterials and coatings for orthopedic and dental applications Berkeley Advanced Biomaterials Inc. $0.6‡ www.hydroxyapatite.com Develops and manufactures calcium-based biomaterials for medical (Berkeley, Calif.) industry, particularly bone grafts

*Conversions per Google as of October 16, 2020. All financial data obtained from company reports unless otherwise noted. ‡Private company or data not available; revenue estimated from dnb.com or google.com.

20 www.ceramics.org | American Ceramic Society Bulletin, Vol. 99, No. 9 Figure 2. Schott Primoceler developed an innovative, extremely precise technology that enables additive-free, room-temperature hermetic glass bonding, enabling Figure 3. NanoRetina NR600 retinal devices to be packaged entirely implant with glass encapsulation.

in glass. Credit: Schott Credit: Schott Primoceler Oy and melts only the very small interface says in a Schott press release.5 “I am very traced back to advances in ceramics and area where the glass wafers meet—an impressed by this experience. I have been glass, as well as other materials. area of just some tens of microns—while working for more than 20 years as an The consequences of miniaturization leaving all other surfaces untouched.” ophthalmologist, but this is the first time I are not limited to better performing and (Figure 2) witnessed a completely blind patient being more innovative devices, however—it also The possibilities of such technology are given back a visual perception.” affects the ultimate bottom line in mod- wide-reaching even within implantable Akin to maturation in the smart- ern heathcare: cost. device applications, but one of the first to phone industry6—where shrinking of “It starts with the surgery itself,” see clinical application is in the eye. components has enabled enhanced func- Herzberg says. “Imagine the pacemaker— For patients with reduced or lost sight tionality in smaller devices—miniaturiza- 30 years ago it was very bulky, so hos- due to retinal degradation, a company tion is an important reason why implant- pitalization time of patients was really called NanoRetina (Herzliya, Israel) able devices such as NanoRetina’s long, increasing healthcare costs. People pioneered an artificial retina device. NR600 are possible today, and it can be cannot go to work, they are on sick leave, NanoRetina’s NR600 implant, which is designed to mimic the functionality of THE SCIENCE AND ART OF GLASS OCULAR PROSTHESES the eye’s highly sensitive photoreceptor Although ocular prostheses are often called cells, is a tiny chip containing an imager, “glass” eyes, many modern such prostheses are 3D neural interface, and embedded pho- actually made of acrylic. tovoltaics to provide power. The device However, prosthetics fashioned from glass—true is completely encased in glass using glass eyes—still exist and are especially preva- Schott Primoceler technology lent in Germany, Austria, and Switzerland, where (Figure 3). more than 90% of ocularists manufacture custom “Without our glass-to-glass laser bond- glass ocular prosthetics. ing technology, this would not have been These glass ocular prosthetics are individual possible because the encapsulated sensor works of glass art, handmade by an ocularist to inside is very heat sensitive. Only with specifically match a patient’s need. Ocularists Credit: glasseyes view; Flickr CC BY-SA 2.0 our technology could we encapsulate it at train for about six years, gaining practical experience in addition to their education, to be able to 1 room temperature,” Herzberg says. master their art. Enabled by glass, NanoRetina’s NR600 Glass ocular prosthetics are uniquely made of cryolite glass, a silicate glass containing the mineral implant entered a small clinical trial of 20 cryolite to provide a white hue that matches the look of a natural eye. The prosthetic is usually patients in Europe and Israel in early 2020 bowl or shell shaped. and already shows promising results. “The Ocularists custom match a prosthetic to the patient’s other eye, using colored class to embed device was activated for the first time, details such as iris color and drawn blood vessels onto the eye, rather than painting them on, thus and the result was amazing: this patient reducing the potential for reaction with the body. All details are part of the 100% glass prosthetic had been completely in the dark for five and are fired into the finished product. years, and she immediately reported seeing Firing produces a very polished uniform surface on the prosthetic to prevent irritation within the an image in the center of her visual field eye socket. And unlike the hydrophobic surface of acrylic prosthetics, which can leave a feeling when the device was activated, and could of dryness for the patient, glass’s hydrophilic surface provides a uniform tear film that keeps the show with her hands the size of the image prosthetic moist. that she saw,” professor Peter Stalmans, A video of the custom manufacturing process is available at https://doi.org/10.3791/60016. n who implanted the trial device and is one 1Kunstaugen-Institut Leipold, http://www.augenprothesen-essen.de/en/wiki/augenprothese-aus-glas. of Europe’s leading retinal specialists, Accessed Oct. 29, 2020.

American Ceramic Society Bulletin, Vol. 99, No. 9 | www.ceramics.org 21 Better bodies with biomaterials and this is very costly for insurance com- market, ceramics’ successful infiltration hindered by the 2001 recall of millions panies. Today pacemakers are getting into joint replacements is most notable of Prozyr brand zirconia ball heads, smaller and smaller because technology for hip replacements. prompted by high fracture rates in patient is getting better and better.” Smaller “Though implantable ceramics have implants. Subsequent failure investiga- devices allow more minimally invasive been in the market for decades, the tion of the manufacturer, Saint Gobain procedures, translating to faster recovery adoption of these materials has really hap- Ceramiques Desmarquest, determined times and shorter hospital stays, which pened in the last 15 years,” says Lucian that a switch in the type of furnace used ultimately help reduce care-related costs. Strong, vice president of CoorsTek to manufacture the implants caused an Technologies and advances that Bioceramics (Grand Junction, Colo.), unanticipated change in temperature continue to allow implantable devices which manufactures ceramic femoral kinetics, resulting in insufficiently densi- to assume smaller forms with enhanced heads and acetabular liners for total hip fied zirconia.11 Although the problem was performance, as well as parallel medical arthroplasty, among other bioimplantable traced back to a manufacturing error, the developments that permit minimally ceramic components. “The adoption is recall significantly marred zirconia’s repu- invasive procedures and improved surgi- coming from the transition away from tation in the market. cal outcomes, are critical components of metals to ceramics due to the superior Many modern ceramic hip joint future healthcare strategies to sustainably wear properties of ceramics, as well as implants now combine the best of and effectively promote the health of patients’ demands for longer and more both worlds with composites that offer growing, aging populations. active lifestyles after joint replacement.” improved properties of strength, tough- Wear of polymer and metal joint ness, and scratch resistance, for example, JOINT IMPLANTS: CERAMICS EXTEND implants can generate debris particles that ones based on zirconia toughened alu- IMPLANT LIFE cause inflammation around the joint, mina (Figure 4). Our joints, the connections between loosening the implant and potentially Beyond material-based considerations, the skeleton’s more than 200 bones, leading to its failure. Potential allergic additional factors also are coalescing to provide our bodies with an incredible reactions to metals as well as toxicity from create a favorable landscape for ceramics capacity for movement. release of metal ions from an implant implants. “Medical care has seen many This ability is perhaps most appreci- into the body are also considerations. transitions over time, but the latest big ated in the face of reduced or lost mobil- These considerations are creat- trend is the move to outpatient care due ity in the joints, often due to stiffening ing a favorable landscape for ceramic to rising costs,” Strong says. caused by conditions such as arthritis. implants, and that shift is evident in Similar to how miniaturization of com- Osteoarthritis, the most common form data from the 2019 annual report of the ponents allowed pacemakers to shrink in of arthritis, represents the single most American Joint Replacement Registry, a size, resulting in shorter hospital stays and common cause of disability in aging bod- database of more than 1.5 million knee lower care-related costs, parallel evolu- ies, affecting an estimated 10%–15% of and hip arthroplasty procedures per- adults over 60 years old.7 formed in the U.S. during 2012–2018. As such, it is no surprise that the Registry data show that for total hip global market for joint replacement, arthroplasty, the number of implants implants, and regenerative product with ceramic heads is increasing and first devices is expected to grow—reaching a surpassed those with cobalt chromium value of $33.6 billion by 2023, growing heads in 2015.9 at a CAGR of 4.8% during 2018–2023.8 This data, however, presents only a Knee replacements constituted the limited picture, as the registry captures largest share of the $26.5 billion joint an estimated 25%–30% of the volume of replacement market (by value, not annual procedures in the U.S. Other esti- number) in 2018, accounting for 33% mates indicate that adoption of ceramic of the market, or $8.8 billion. Hip hip implants is already much higher in replacements were the next largest share, some parts of the world—more than 50% accounting for 28% of the market or of hip implants performed in European $7.4 billion, followed by spinal implants countries like Austria, France, Germany, (20%; $5.2 billion) and then extremities Italy, and Switzerland use a ceramic ball reconstruction, which comprises implant head, while 72% of total hip replace- Credit: CoorsTek Bioceramics devices for the shoulder, elbow, wrist, ments in Asian countries such as South Figure 4. Femoral head and acetabular digits, and ankle joints. Korea have an alumina ball head.10 liner cup for total hip arthroplasty, manu- At all of these locations, ceramic A large proportion of total hip replace- factured by CoorsTek Bioceramics. The implant is made of CeraSurf-p, an alumina implants compete with those made of ment ceramic implants are historically zirconia matrix composite that incorpo- alumina, although zirconia is used as polymers, metals, and combinations rates advanced toughening mechanisms thereof. Due to length of time in the well. Acceptance of zirconia was severely to improve the material’s performance.

22 www.ceramics.org | American Ceramic Society Bulletin, Vol. 99, No. 9 tions also occurred for joint replacements. “Generally speaking, technical ceramics are a component of a larger medical implant. Modern ceramics are engineered to be so strong that they are allowing for design changes to the entire device,” Strong explains. “They have been optimized to the point where they are impact- Credit: Coorstek Bioceramics Figure 5. Due to excellent their wear rates, ing the surgical procedures, which are ceramics can also be found in cervical disc Credit: SINTX now quicker and more efficient. In total Figure 6. Silicon nitride spinal devices bearing surfaces for spinal total disc replace- manufactured by SINTX. hip arthroplasty, ceramics are a critical ments. This one, by CoorsTek Bioceramics, is part of the overall device, which has been made of alumina zirconia matrix. market. Silicon nitride spinal fusion designed around the next generation in devices manufactured by SINTX (Salt surgery. With the current trend toward polymers such as polyetheretherketone Lake City, Utah)—the only FDA-registered robotics, these designs allow for faster (PEEK) provide good value—these mate- and ISO-certified silicon nitride medical and more accurate outpatient surgical rials do not offer perfect solutions in the device manufacturer in the world—and procedures that previously would require spine, where integration with existing sold through CTL Amedica are work- significant time in hospital recovery.” tissue is particularly desirable for preserv- ing their way into this market (Figure 6). These advancements not only ing functionality of the spine and main- Silicon nitride is not only bioactive, improve patient outcomes but also help taining longevity of the device. antiviral, and antibacterial but also pro- reduce healthcare costs, factors that are “Overall, the need of the hour is to motes bone growth, providing an effective intimately intertwined. develop materials that demonstrate both orthopedic solution. biomechanical applicability and biocom- Although the material currently consti- SPINAL IMPLANTS: SECURING WITH patibility while being user friendly in a tutes a small portion of the overall market GLASS OR SILICON NITRIDE surgical environment,” according to a for spinal fusion devices, data indicates Because the spine provides a critical bal- 2017 article on trends in spinal surgery silicon nitride has significant potential, ance of flexibility and stability to the body, materials.13 So it is not surprising that as the company reports there were fewer any modifications to the spine ideally also this field is also starting to realize the than 30 FDA-reported adverse events must balance those same properties. potential of ceramics and glass. despite more than 35,000 human spine Spinal implant devices stabilize and For instance, Mo-Sci (Rolla, Mo.) is implantations over 10 years.10 strengthen the spine in various ways, developing multicomponent bioresorb- SINTX anticipates many additional often by securing vertebral elements and able spinal bone grafts from bioactive orthopedic applications for silicon inserting implants to shore up the inter- glass—containing one bioactive glass nitride, such as dental and craniofacial vertebral space (Figure 5). But that need formulation that dissolves more quickly applications as well as joint replacements. for flexibility and stability makes spinal and contains compounds to stimulate “There’s a lot of concerns that metals cor- devices challenging to design. vasculature growth (e.g., copper and zinc rode in the body. As you’re putting hips For instance, the articulation surface elements) in early stages of healing, and into younger and younger patients who for a total disc arthroplasty must not another bioactive glass formulation that are going to live longer, you’re not look- only be functional, it must be designed forms a porous silicate glass scaffold that ing at 20-year outcomes. You’re interested to account for an estimated device life dissolves more slowly to provide support in 30- and 40-year outcomes, and there of more than 40 years. Considering the while natural bone formation gradually ceramics have a very special role,” says estimated number and amplitude of load replaces the graft. Sonny Bal, president and CEO of SINTX. cycles a lumbar disc undergoes annu- “This bone graft has shown really nice For craniofacial applications, custom- ally—based on an average adult bending improvements in spinal fusion rates, and ized repair of defects with 3D-printed an estimated 125,000 times and taking it actually isn’t even on the market yet,” patient-specific implants is a possibility 2 million steps in that year—a disc says Steve Jung, chief technology officer that SINTX has in mind, according to implant is expected to endure some of Mo-Sci. “Mixing to get this benefit Don Bray, vice president of business 85 million cycles of loading during its from this material and this benefit development at SINTX. “If someone lifetime without wearing down.12 from this material is sometimes a better has a severe accident and you need to So these devices demand incred- option than trying to find this one mate- rebuild the facial bones and structure, ibly high-performance and long-lasting rial that could do it all. Sometimes you you would want to do a CAT scan and materials. While the usual biomedical have to accept that there are just two make an exact fit. In the spine you can materials have long been used in spinal really great materials you can put togeth- use some standard sizes. But because of implant devices—metals such as stain- er and get what you want from each.” the shape of the face, you can’t—and we less steel, titanium, and cobalt-based Beyond bioactive glass, other materials think 3D printing there with our silicon alloys offer strength; high-performance also have their sights set on the spinal nitride is key,” Bray says.

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is interested in making the investment

(b) to further develop applications for additively manufactured bioactive glass. (a) Lithoz’s technologies can print complex geometries such as high-resolution (d) lattice structures with openings just several hundred microns wide—optimal scaffolds to promote interaction and integration with living tissues—so medical applications are one promising direction (c) (Figure 7). For instance, such bioceramic scaffolds could be used to repair bone defects due to injury or disease. While ceramic and bone are a perfect (e) match materially speaking, design of bio- (f) ceramic scaffold structures is challenging because they must provide both porosity

Credit: Lithoz and mechanical strength, properties that Figure 7. 3D-printed medical devices manufactured with Lithoz CeraFab System printers. From left to right: a) Mandibular implant (white: zirconia, blue: hydroxy- often come at a tradeoff. Fortunately, apatite), b) spinal implants (grey: silicon nitride, white: tricalcium phosphate), natural bone can provide some inspira- c) front jaw bone augmentation (blue: hydroxyapatite, white: bioactive glass), tion. Bone’s structure consists of an d) cranial implant (tricalcium phosphate), e) zirconia crowns (native and colored), outer layer of dense cortical bone filled f) dental implants and abutment (grey: silicon nitride, white: zirconia). with porous and spongy inner trabecular bone, a multimaterial strategy that uses “It’s a very critical area, so having an report, the 2019 additive manufacturing two different forms to provide two dif- antibacterial implant that would you could industry was worth some $11.867 billion. ferent components of bone’s function. make exactly for the person is where we Medical and dental applications account Lithoz is developing multimaterial think this is going to go,” Bray adds. “And for about 11% of that market, and dental 3D-printed implants that provide both we don’t think it’s that far off.” in particular represents a large growth seg- porosity to promote tissue regeneration Because of silicon nitride’s favorable ment in the latest report.14 and mechanical stability to support antibacterial and biological properties, Additive manufacturing company a bone defect. These multimaterial SINTX also is developing techniques to Lithoz GmbH (Vienna, Austria) is famil- implants incorporate a strong outer incorporate silicon nitride into devices iar with the potential of the technology layer for structural support during the and products made of other materials as for medical and dental applications. initial healing phase, composed of a well. For example, silicon nitride can be Lithoz’s lithography-based ceramic manu- ceramic material with good mechanical mixed into polymer-based products or facturing technology 3D prints complex stability such as zirconia, with a porous coated onto titanium devices to enhance structures layer-by-layer using a photo- inner scaffold of bioresorbable ceramic biocompatibility of those surfaces, pro- curable polymer–ceramic slurry. After substrate such as tricalcium phosphate mote healing, and prevent infection and printing, green parts are debinded and or hydroxyapatite. The inner material spread of viral diseases, according to Bal. sintered to remove the polymer, leaving more closely matches the inorganic “We are looking at 3D processing proce- fully dense ceramic parts. component of bone, and its porosity per- dures that we can commercialize, in which Lithoz developed both the expertise mits cell attachment and penetration of we put a very tenacious micron-level coat- and the custom printers to additively blood vessels, allowing the body to heal ing of silicon nitride that supercharges the manufacture a diverse array of ceramic and replace the bioresorbable substrate metal and makes it antibacterial,” he says. materials, everything from piezoceram- with natural tissues over time. ics to regolith, and certainly including Such multimaterial implants could 3D PRINTING: A TECHNOLOGY WITH ceramics with medical applications be used to repair many types of bone LAYERED MEDICAL POTENTIAL such as alumina, zirconia, silicon defects, such as those in the jawbone. nitride, hydroxyapatite, and tricalcium Multimaterial implants Critically, Bomze says, the material’s phosphate. Daniel Bomze, head of the resorption rate can be tuned to the area At the intersection of medical care Lithoz’s medical business unit, says the of the body being targeted. “The ideal and additive manufacturing lies tremen- company also has success printing with would be that the regrowth, the new dous promise to completely change how bioactive glass. “We have produced tissue forms at the same speed as the we approach health strategies to replace, several parts and some slurries already implant is being resorbed. So you have enhance, and restore function of the successfully with bioglass. So we know it the overall volume and stability, and the human body. works,” he says. Now, Bomze says Lithoz whole healing time is the same by tuning According to the annual Wohler’s is waiting for a commercial partner who

24 www.ceramics.org | American Ceramic Society Bulletin, Vol. 99, No. 9 this artificial material and the natural material,” he says. Although the individual components of these implants were implanted into a small number of human patients, with good results so far, the multimaterial implant is currently a proof-of-concept. And although the current design is printed into two separate steps, Lithoz has bigger plans for the future. Figure 8. A multicomponent demo part made “The future will be printing it simul- of alumina (outside) and zirconia (inside, taneously, in one single step—you could Lithoz writing) printed on a CeraFab Multi print the cage and the inner part at 2M30. Both materials were printed in one run the same time and then sinter them simultaneously, and the part is sintered. together,” Bomze says. “You can probably Credit: Lithoz make even more sophisticated materials, ent raw materials (Figure 8). This ability ing ceramic-based biomaterials at room for example a sandwich structure with an affords new functional applications, temperature, with no additional post- inner part of hydroxyapatite, then a shell such as printing multiple materials in a processing sintering steps required— of zirconia, and then a tiny outer coating single layer and allowing gradual compo- affording the ability to incorporate or a third layer again of hydroxyapatite to sitional variation from one material to organic molecules such as proteins, facilitate ingrowth of the of implant. And the next.15 drugs, and antibiotics into the materials here we’re making really rapid progress.” 3D-painting themselves before printing. In that vein, Lithoz released in As noted in a May 2019 Bulletin arti- Additive manufacturing is a diverse September 2020 a new multimaterials cle,16 “3D-painting is a materials-centric technology, so Lithoz’s lithography- 3D printer called the CeraFab Multi advanced manufacturing technology that based technique is one of many differ- 2M30. The printer is similar to the permits nearly any material to be trans- ent approaches. company’s other offerings but now formed into a 3D-printable ‘3D-paint’ Another company, Dimension Inx includes two vats to provide the ability via simple, room-temperature extrusion (Chicago, Ill.), is innovating with print- to simultaneously print with two differ- without the need for support materials,

BREATHALYZERS: ANOTHER WAY TO DETECT COVID-19 In the fight against COVID-19, the main tech- includes advances on nanomaterials for detect- nique used to collect samples is a deep nasal ing specific breath gases at concentrations that swab, a procedure doctors describe as moder- can make a diagnosis. ately uncomfortable but some patients describe Gouma says her team initially tested the new as “being stabbed in the brain.” breathalyzer by using gas canisters that were Testing methods that are more comfortable and mixed to simulate the breath gas mixture as more easily administered would certainly be a result of COVID-19 infection. However, they appreciated by patients and physicians alike, have since moved to conducting human testing and researchers have explored saliva testing and have been testing at various COVID-19 test- as an alternative, with some promising results. ing sites around Columbus, Ohio. However, according to Edward Orton, Jr., Chair In mid-September, they reported initial results in Ceramic Engineering Pelagia-Iren (Perena) from the ICU-focused human testing at the Gouma at The Ohio State University, breathalyz- Ohio State Wexner Medical Center. The results ers may be an even easier and readily acces- showed the breathalyzer could detect acute sible way to administer tests. Credit: Perena Gouma and M. Stanacevic. cases of COVID-19 and can monitor the severity Breathalyzers use selective gas sensing ele- The portable, battery-operated breatha- of the disease. ments to detect certain biomarkers in breath lyzer prototype to detect COVID-19 The researchers currently are seeking FDA emer- that signal disease. Compared to swab-based developed at The Ohio State University. gency-use authorization for the breathalyzer. testing methods, breathalyzers are noninvasive, diseases a few years ago, and she has worked nonintrusive, and can deliver a result in dozens extensively the past few months to use that For more information on Gouma’s study, as of seconds. knowledge to design a breathalyzer that detects well as other breathalyzer studies taking place at Northeastern University, check out a recent Gouma has explored the use of breathalyzers COVID-19. Wired story on the topic at https://www.wired. for medical diagnostics since 2003. She started The in-development COVID-19 breathalyzer com/story/could-breathalyzers-make-covid- investigating the development of breathalyz- uses ceramic sensors to target biomarkers that testing-quicker-and-easier. n ers aimed specifically at detecting infectious give a response specific to that infection, and it

American Ceramic Society Bulletin, Vol. 99, No. 9 | www.ceramics.org 25 Better bodies with biomaterials Credit: Adam Jakus, Dimension Inx

Figure 9. Anatomical structures display a handful of possible struc- Credit: Adam Jakus, Dimension Inx tures that were 3D printed by Dimension Inx with Hyperelastic Bone: Figure 10. A sheet of Dimension Inx’s 3D-printed Hyperelastic (clockwise, from top left) spine, femoral head, mandible, and pelvis. Bone, which is flexible despite being 90% ceramic. powder-beds, resin-baths, cross-linking, Jakus explains. Human bones contain control aspects of the process, showing or curing.” 60%–70% dry weight of crystalline that it can demonstrate consistent results. In the 3D-painting technique, a hydroxyapatite, bound by collagen and “So a lot of our efforts throughout 2020 powder-based material is mixed with other structural and functional proteins. have been establishing new quality con- elastomer and solvents; after extrusion “But the end result is actually flexible trol systems and quality manufacturing through a nozzle, the finished printed and cuttable and shapeable, which you systems around design and synthesis product requires only rinsing and steril- wouldn’t really expect for a something of these new materials as well as the izing. The flexibility of the technique that’s mostly ceramic.” 3D-painting process itself,” he says. means that in addition to 3D printing That flexibility is because of That includes establishing consistent structures out of 3D-paints, the same Hyperelastic Bone’s unique microstruc- and detailed manufacturing processes strategy could also be used to coat prod- ture, which forms as evaporants vapor- and identifying and mitigating risks—all ucts manufactured via other techniques ize from the printed material after it is part of the company’s preparations and out of other materials. extruded through a printer nozzle. The toward seeking FDA approval for Importantly, 3D-painting can be rate of evaporation tunes precipitation Hyperelastic Bone devices. applied to almost any material, includ- of the elastomer, forming an optimized 3D printing inherently conjures ideas ing ceramics. “3D-painting is materi- structure in the printed material.17 of patient-specific printed implants. And als agnostic. It’s not dependent on “A very specific microstructure really while that is an eventual direction for what you’re making or what material allows the different components of the Dimension Inx, the company is starting you’re using,” says Adam Jakus, co- composite, the ceramic and the resorbable with a more practical pathway—and one founder and chief technology officer at polymer, to play off each other and move common for biomedical innovations—by Dimension Inx. around and then return to their original targeting mass-produced implants of As one example of the 3D-painting form without breaking,” Jakus says. Hyperelastic Bone, a collection of stan- technology, Dimension Inx’s bone- Hyperelastic Bone also is micropo- dard shapes like “strips or squares or specific 3D-paint formulation, called rous, which provides excellent osteo- blocks,” Jakus says. “We are introducing Hyperelastic Bone®, is primarily ceramic conductivity and biocompatibility. “If a new material in a new manufactur- yet still incredibly flexible, offering sig- it’s intended to regrow bone, the body ing process. So I think it’s important to nificant potential for bone implants. tissue needs to be able to access that get the regulatory agencies, the FDA, Hyperelastic Bone can be printed in material on the microstructure level and surgeons, everybody comfortable with specific structures (Figure 9) as well as transform it,” Jakus says, although the the material and the process first so they porous scaffolds and sheets that could be porosity can have a drawback. “But it’s are then willing to take that next step to cut and custom-fit in the operating room a balance if you want structural integrity patient-matched implants.” (Figure 10). and you want bioactivity. Those things That acceptance is a considerable issue “The really interesting thing about are in conflict all the time.” in the medical industry—you not only Hyperelastic Bone is that it’s 90% Since the technology is relatively have to prove that a device or technology ceramic, which is technically more well-established at this point, Jakus says works (see sidebar: Regulating the pace of ceramic than is in our actual bones,” Dimension Inx is now working on quality medical innovation), but you also have to

26 www.ceramics.org | American Ceramic Society Bulletin, Vol. 99, No. 9 convince medical professionals to use it Infiltrating a site like the craniofacial Biomaterials were once designed to as well. And that can be a major barrier, space can then be a strategic initial target minimize interactions with the body especially for new medical innovations. application of a new technology to gain and to eliminate any potential adverse “The technology is the easy part,” acceptance before expanding to addi- reactions. But starting with Larry Jakus says. “And even after you identify tional sites and applications. Hench’s discovery of bioactive glass a technology that addresses an actual Another consideration that makes 50 years ago,18 a more modern perspec- need, getting surgeons to venture out the craniofacial segment attractive for tive for biomaterials no longer attempts their comfort zone is very hard.” If an innovation in additive manufacturing, to eschew cell biology. existing clinical solution is trusted and especially with bioresorbable materials, “Design of a new biomaterial should works relatively well, medical profession- is that these surgeons treat many pediat- always consider the need of the cells, als often are not keen to change a pro- ric defects. “So they’re most excited to because the cells are the engineers of our cess, especially if the solution does not use new materials, ceramic or not, that body,” says Aldo Boccaccini, professor offer additional profit or patient benefit transform over time and grow with the of biomaterials and head of the Institute or it requires the professional to master patient,” Jakus says. of Biomaterials in the Department a new technique. Introducing a new of Materials Science and Engineering product also comes with some inherent TISSUE REGENERATION: THE SOFTER at University of Erlangen-Nuremberg risk, which medical care is designed to SIDE OF BIOMATERIALS (Erlangen, Germany). minimize, for good reason. In terms of the body’s natural materi- Many biomaterials now aim to not One sector, however, where medi- als, ceramics and glass are most analo- only stand in for living tissues when they cal professionals are often more willing gous to bone and tooth enamel—so it need to be repaired or replaced, but the to take modest risks is the craniofacial is not surprising that there are so many materials play a more supportive role space—which is why medical innovations orthopedic and dental applications for in actually helping the body perform its often target this site. ceramics and glass (see sidebar: Ceramics own healing—more like an assist rather In particular, additively manufactured used in dentistry). than a complete substitution. That guid- medical technologies often focus on But modern developments in nano- ance can be used to mediate processes craniofacial applications because these technology, particularly the ability to such as wound healing and to rebuild defects are non-load bearing and highly engineer nanosurfaces, nanoparticles, damaged or missing tissues, broadly individualized. In addition, there are few and nanoscaffolds, as well as more contributing to the overall field of tissue existing off-the-shelf products to treat nuanced understanding of cell biology engineering, or regenerative medicine. craniofacial defects, so these medical pro- are together reshaping how we think In terms of the future of healthcare, fessionals are often more willing to take a about the potential of biomaterials. regenerative medicine is a big business. slight risk with innovative new solutions. The global market for tissue engineering

REGULATING THE PACE OF MEDICAL INNOVATION While there is no shortage of innovative ideas devoted to testing and documenting effective- new device—such observation trials would for medical applications, bringing such innova- ness and safety in both lab settings and in completely stifle innovation and prohibit en- tions to the market is a whole different story. animal models. trance of any new product on the market. “The medical market is slow and steady in In the U.S., where the FDA regulates the ap- Instead, to develop materials for the future, terms of innovation,” says Lucian Strong, vice proval process, bringing a medical device to we need robust short-term outcome proxies president of CoorsTek Bioceramics (Grand market takes on average 3–7 years.1 Although that can predict long-term behavior, Bal says. Junction, Colo.). “While new applications or this process unavoidably slows the pace of “That’s the Holy Grail.” processes may demand new materials, there is innovation, these pathways are critical to Bal made the analogy to how NASA uses algo- a well-defined process that is governed through maintain safety and minimize potential harm to rithms and modeling to predict the outcomes of the regulatory bodies around the globe. There human health. its missions. There are no practice runs when is no simple introduction of a new material Yet even once clinical data does provide accep- sending a rocket to Mars—NASA incorporates that will be implanted into a patient. Clinical tance for a material, the story is still not over. knowledge and modeling to maximally reduce data, proven over numerous years and multiple the margin of error. And that, he envisions, is patients, is necessary for any new material to “The increasing longevity of the human race, where biomaterials need to go. gain acceptance.” younger patients undergoing surgical inter- ventions, all points to a future in which we as “Instead of experimenting with humans, we Collecting such data takes considerable time, scientists need to understand the long-term need to be able to predict how a biomaterial will but it is a critical component of the regulatory interaction of the implant with the body,” says behave in the body just like NASA does—be- processes to ensure that biomaterials and B. Sonny Bal, president and CEO of SINTX. cause there’s no room for mistakes. You do it devices are safe and effective once implanted once, and that patient has to live with it. You into human patients. And even before the Of course, it is not feasible to wait decades can’t have failures,” he says. n clinical data, much additional time must be first while collecting long-term outcomes for every 1G. A. Van Norman, “Drugs, devices, and the FDA: Part 2: An overview of approval processes: FDA approval of medical devices,” JACC: Basic to Translational Science, 1[4] 277–87 (2016). DOI: 10.1016/j.jacbts.2016.03.009

American Ceramic Society Bulletin, Vol. 99, No. 9 | www.ceramics.org 27 Better bodies with biomaterials and regeneration was valued at $24.7 still being realized today. When in con- anisms, the potential exists for bioactive billion in 2018 and is predicted to reach tact with body fluids, bioactive glasses glass compositions and properties to cata- $109.9 billion by 2023, representing an dissolve and release ionic dissolution lyze a diverse array of cellular responses, impressive CAGR of 34.8%.19 While products such as biologically active ions precisely tuned to the target tissue and bone is a significant focus of this market, within the body. Cells, in turn, respond the desired effect in that tissue—whether it encompasses soft tissues as well, such as to these ionic products, some of which that is modulating an immune reaction, strategies to repair damaged cardiac and stimulate growth of new blood vessels in prompting tissue regeneration, or stimu- gastrointestinal tissues or engineer vascu- the tissue, a process called angiogenesis. lating release of growth factors to guide lar, muscle, neural, and skin tissues. Blood vessels nourish developing tissue stem cell differentiation. Likewise, there is potential for many with oxygen and nutrients and remove “Understanding genetic upregulation different types of materials in this broad waste products, so the angiogenic and activation by ionic stimuli released field. “In the field of regenerative medi- response is part of what makes bioactive from bioactive glasses offers the possibil- cine and tissue engineering, there is no glass so attractive for tissue repair.20 ity of developing patient-specific thera- one material that is going to tackle all But ionic dissolution products also do pies, a huge challenge for the aging pop- the problems,” Boccaccini says. And more than stimulate angiogenesis—these ulation,” per a 2015 Bulletin article on many of the ceramic- or glass-based strat- products alter gene expression patterns bioactive glasses.21 egies to heal tissues actually combine in nearby cells, shifting signaling path- One of the more familiar and clini- them with organic materials, in polymer ways that orchestrate every cellular func- cally approved applications of bioactive composites or hydrogels, for example. tion, such as cell migration, prolifera- glasses for soft tissues is in wound repair, Although bioactive glasses were tion, and differentiation. with products such as a cotton candy-like discovered half a century ago, their Although we are just beginning to borate bioactive glass fiber matrix to heal potential within regenerative medicine is unravel some of these biomolecular mech- advanced wounds.22

CERAMICS USED IN DENTISTRY Ceramics are ubiquitous in the $10.7 billion U.S. polyalkenoate cementb material to restore the standard tooth restoration for severely dam- dental industry,1 with applications in prosthet- tooth form. age teeth because of their greater durability ics, fillings, orthodontic appliances, cosmetic When the disease progresses into the pulp, a and more natural aesthetic. Today, all-ceramic products, process materials, preventive products, medication that induces the pulp tissue to build a crowns—such as alumina, lithium disilicate, toothpaste, and more. Below are some highlights protective barrier of reparative dentine is needed. and yttria-stabilized tetragonal zirconia—are of the roles that ceramics play in this industry. Calcium hydroxide-containing materials used to the most common crown type because of their be the standard material used for this purpose, but strength, ease of fabrication, and aesthetics. Dental caries: From prevention now tricalcium silicate cements, which are based Tetragonal zirconia with 3% yttria dominates this to treatment on the same materials as white Portland cement, market due to its high strength, but zirconia with Dental caries, commonly known as tooth decay, are the “gold standard.” (These cements are set higher yttria formula are also in use due to better is the most common bacterial disease of children with a matrix that includes calcium hydroxide.) aesthetics, despite their diminished strength. and adults worldwide.2 Formerly, tooth loss If the pulp becomes irreversibly infected, a root Whenever a temporary or permanent crown or due to bacteria attacking the tooth enamel was canal procedure is required. In this proce- bridge is placed, dental cements are needed. inevitable, but advances in dental materials and dure, the pulp is removed and is replaced by a Numerous ceramic- and glass-containing dental techniques during the last few decades have combination of rubber points shaped like a root cements are used in dentistry, but the original greatly reduced chances of this outcome. canal and sealed with another material. The cements were all based on zinc oxide. More Plaque removal and teeth cleaning at home and trans-polyisoprene rubber points are usually recently, glass-ionomer cements evolved from by hygienists is the first line of defense against filled with zinc oxide and barium sulfate. The the original silicate filling materials in the mid these bacteria. Toothpastes contain many sealing material comes in a variety of polymer 20th century and remain popular because of their ceramic powders ranging from stannous fluoride, and ceramic matrices, ranging from epoxy to zinc temporary fluoride release, which deters caries potassium nitrate, and several calcium phos- oxide–eugenol. The newest sealers are based on from forming under a crown. Resin-modified phate compounds. Bioactive glass is also present tricalcium silicate powders. Sometimes, glass glass-ionomer cements and compomers are in some toothpastes, to promote remineralization fiber-reinforced composite posts are inserted in also advantageous, by combining light-curable of the enamel. Sodium bicarbonate is often used a root canal after a root canal procedure to help polymers from composites with limited fluoride by hygienists to more thoroughly remove plaque, restore tooth function. ion release from the glass ionomers. and pumice is sometimes used as well. When a majority of the anatomy of a tooth is When bacterial attack progresses into the Tooth extractions: Replacing the lost, the anatomy is restored with a crown. Gold missing teeth enamel, a dentist will seek to remove the soft- foil and its alloys were the materials tradition- ened tissue and restore tooth anatomy. Small to ally used for crowns, but in the 1950s, porcelain Periodontal diseases and tooth fractures may medium bacterial lesions (cavities) are treated enameled crowns and bridges became the lead to tooth extraction. Dental implants, or posts with ceramic composite fillinga material or glass surgically placed into the jawbone, are increas- aUrethane polymers filled with about 40–70% by weight of ceramic powders, which may include radiopaque glasses, fumed silica, or quartz in combination. Requires bonding agents such as silane and a polymer primer to induce adhesion. bIn other words, glass-ionomer, composed of fluoroaluminosilicate glass powder reacted with a polyacrylic acid liquid, which bonds to tooth structure. Used for restoring tooth anatomy plus permanent cementation of crowns, bridges, inlays, onlays, posts, and orthodontic appliances.

28 www.ceramics.org | American Ceramic Society Bulletin, Vol. 99, No. 9 “But you can also think of internal on the market. “They’re making these Randel Mercer, chief technology officer wounds, such as adhesives with hemostatic products better by the addition of bioac- at CoorsTek. “One exciting avenue ability for coating internal wounds where tive glass,” Jung says. CoorsTek has been working on is the there is a lot of bleeding,” Boccaccini says. Jung says that in veterinary medicine, use of engineered ceramic cell cultur- “Here I think yet is an open area for the there also have been some indications ing devices. Our product, Cerahive, is applications of [bioactive glass], either as a that bioactive glass can also repair used to grow human tissue cells in an fiber or mesh or in composites.” tendons and ligaments. “To me, that environment that mimics the growth As research continues to characterize kind of outcome is really what gets you environment in the human body.” These how cells respond to the unique materi- thinking about sports injury-type situa- porous ceramic substrates line the bot- als as well as the underlying biomecha- tions—if you blow a ligament, could we tom of a cell culture dish to support 3D nisms of these responses, soft tissue develop a technology to help to heal cell cultivation, allowing in vitro growth applications of bioactive glass will also that back together?” he says. of cell spheres (Figure 11). “The future continue to expand. Beyond being implanted within the potential to ‘manufacture’ specific tis- Mo-Sci’s Steve Jung says that bioactive human body to aid tissue regeneration, sues in the laboratory could be used as glass is experiencing increasing integra- ceramic and glass materials can also be a source for repairing damaged tissue in tion in medical products due to the similarly used to grow tissues outside of humans,” Mercer says. material’s recognition as a “premium the body, with the vision that these tissues material” and its ability to intimately could eventually be harvested and implant- LOOKING FORWARD—A GLIMPSE OF interact with tissues. Bioactive glasses ed into or on the body as appropriate. FUTURE HEALTHCARE are being combined with other materials “The possibilities for ceramic tech- So what does the future of medical to make new products as well as being nologies for improving the health and care look like, and how do biomaterials integrated into existing products already wellbeing of mankind are vast,” says fit into that future?

ingly used to replace single teeth and to support bound in rubber; others are used in paste form. “Dentistry often follows the innovations in other bridges and dentures. Implants used to be exclu- “Of course, most of the equipment used in den- industries or adopts materials used in other sively titanium, sometimes with a hydroxyapatite tistry would not be possible without ceramics, fields,” Primus says. (ceramic) coating. However, tetragonal zirconia from microscopes and cameras to curing lights For example, computer-aided design and is gaining popularity despite its higher cost due to air turbines handpieces; from piezoelectric computer-aided manufacturing (CAD/CAM) are to its improved biocompatibility. devices, to general electronic devices, to office examples of innovations from other industries When implants are not possible, a partial or full scheduling and case record software and com- adopted for dental applications beginning in denture may be made for a patient. Today, most puters,” says Carolyn Primus, medical device the 1980s.3 CAD/CAM dentistry is becoming a dentures are composed of pressure formed consultant and the 2020 Larry Hench awardee widespread method for making ceramic dental acrylic base with injection molded acrylic teeth. for Bioceramics. crowns in a dental office. However, in some regions of the world, porcelain Additive manufacturing is also being adopted for Future of dental ceramics teeth in an acrylic base remain popular. (Por- dentistry. Fabrication of dentures and temporary celain was the standard denture material in the Biocompatibility is a top priority for medical restorations are leading the way for additive early 20th century.) devices, and ceramics excel in biocompatibility manufacturing. Lithoz GmbH (Vienna, Austria) compared to polymers and metals. On the other is helping to lead the adoption of additive Other applications: Brackets, hand, durability is a key concern for ceramic manufacturing for dental purposes with their abrasives, equipment restoratives in dentistry, particularly composite lithography-based CeraFab 7500 Dental and Orthodontic brackets are commonly made of ceramics. Current research on zirconia, for CeraFab System Series ceramic manufacturing stainless steel, but sapphire, tetragonal zirconia, example, looks to optimize the strength and machines. Ivoclar Vivadent (Schaan, Liechten- and polycrystalline alumina (with no glass bond- appearance of zirconia by exploring variations in stein) is also exploring additive manufacturing) are also used to manufacture orthodontic the stabilizers for the tetragonal phase. Ceramic ing with their PrograPrint PR5, a digital light brackets because of their aesthetic appeal (they nanoparticles are another subject of much processing-based stereolithography printer. make the brackets less obvious). Ceramic coat- research, as nanoparticles offer a way to provide As these technical innovations allow people to ings such as rhodium oxide are also used on orth- unique biological responses. Nanoparticles are retain more teeth, the dentistry field will con- odontic wires to disguise the orthodontic device. not new in dentistry, however—silica nanopar- tinue to grow, and the opportunities for ceramic ticles have been used for decades in composites Diamonds, tungsten carbide, and alumina and and glass materials along with it. n silica abrasives are essential for dentistry to and toothpastes. remove tooth structure and to polish or adjust any Compared to other fields, manufacturing in dental restorative or denture. Some abrasives are dentistry happens at a small scale. As such,

1Dental products & materials.” Freedonia Group, January 2016. https://www.freedoniagroup.com/industry-study/dental-products-materials-3359.htm 2Kassebaum NJ, Bernabé E, Dahiya M, Bhandari B, Murray CJ, Marcenes W, “Global burden of untreated caries: a systematic review and metaregression,” Journal of Dental Research, 94(5): 650–658 (May 2015). doi: 10.1177/0022034515573272 3Klim J and Corrales E. (2008). “Innovation in dentistry: CAD/CAM restorative procedures.” https://www.semanticscholar.org/paper/Innovation-in-Dentistry-%3A-CAD-%2F-CAM-Restorative-Corrales/ f80ede5fc034b50afe972b7b7e15435108c7c8d5#paper-header. Accessed on Oct. 29, 2020.

American Ceramic Society Bulletin, Vol. 99, No. 9 | www.ceramics.org 29 Better bodies with biomaterials

turing different material types together to match the really different material types in the body.” Another systems-level approach that will certainly shape the future of healthcare is smart implants. Miniaturization of devices, enabled by advances in the materials themselves, provided the feasibility for tiny sensors that can be implanted within the body to track an array of biological parameters on-demand. Such sensors provide the ability to track those parameters continuously, rather than sporadic measures taken at a doctor’s office or hospital, and monitor for any changes that could signal a potential health problem. Such rich data provides a more comprehensive view of a patient’s health as well as the ability to respond immediately to a Figure 11. CoorsTek’s Cerahive 3D cell cultivation system. Small porous ceramic discs placed in the bottom of a cell potential disturbance in that health. culture disc allows growth of 3D cell spheres in vitro. Credit: CoorsTek According to Schott’s Jochen Herzberg, smart implants have a promi- “The medical industry is constantly innovation is technologies that address nent place in the future of medical care searching for new, better, and more cost- multiple different tissues simultaneously. not only because they provide better effective solutions, and advancements Although an isolated tissue-specific monitoring but also in terms of reducing in the medical industry are moving at a approach often guides biomaterial devel- healthcare spending, by reducing trips pace so much faster than just a few years opments, components of the human to the doctor or hospital and by inform- ago due to the introduction of advanced body operate together in systems on sev- ing more strategic medical intervention materials. With climbing healthcare eral different scales. when necessary. costs combined with the move from “If you look at everything in isolation, “A trend that is very visible right now inpatient to outpatient procedures, there there are solutions that already exist. is smart implants and remote monitor- is a pull from the market for better mate- They may not be the best solutions, but ing of patients to reduce hospitalization. rials,” says CoorsTek’s Lucian Strong. there are ways to treat individual tis- For example, in-line measurements of Ceramics and glass clearly fit into that sues,” says Dimension Inx’s Adam Jakus. vital signs like blood pressure inside of future vision not only because of the However, most injuries or conditions your body, with smart computers inside role of established products such as joint involve multiple tissues, so more com- your body communicating with your implants but also due to entirely new plex solutions are often required. doctor without being hospitalized,” forms and functionalities of the materi- “This has been a driving force for our Herzberg says. als that are just starting to be discovered, technology for a long time, and we set Glass is already used in several differ- realized, and matured. up a manufacturing technology where all ent components of such devices, includ- “I absolutely believe that ceramics the materials are complementary to each ing hermetic seals, but its optical trans- and bioactive glass have a really strong other,” Jakus says about Dimension Inx’s missivity offers compatibility in terms future, and their areas of use are going to 3D-painting platform. “So we can manu- of data transmission (see sidebar: Could diversify in a big way,” says Mo-Sci’s Steve facture a bone material with a muscle future bandages not only be smart, but also Jung. “Bioactive glass is 50 years old, but material and with a ligament material, made of glass?). we’re still finding new ways to use it all so that in the future you could make a Yet tiny implantable devices also can the time. Old materials used in new ways multitissue implant.” do more than just sense and monitor— or in combination with new techniques I Such strategies will inevitably need to they can also be designed with the capa- think is the wave of the future.” leverage properties and strengths from bility to intervene as well, for instance by Some of those new ways, combina- multiple different materials. “This could delivering a therapeutic. tions, and techniques are highlighted in be partially ceramic, partially polymer, “This is very fast moving technol- this article, but potential extends much, partially biological, even partially things ogy. The idea is to replace conventional much further as well. like graphene and graphite for electrical medical therapies with active implants One particular area ripe for future conductivity,” Jakus adds. “So manufac- so that you avoid overmedicating your whole body, for example by replacing

30 www.ceramics.org | American Ceramic Society Bulletin, Vol. 99, No. 9 COULD FUTURE BANDAGES NOT These data-based monitoring strate- 8 BCC Research, “Advanced orthopedic tech- gies extend beyond implants as well, nologies, implants and regenerative products ONLY BE SMART, BUT ALSO MADE (HLC052D),” August 2018. according to a Deloitte Insights report OF GLASS? 9 23 American Academy of Orthopaedic Surgeons, on the future of health. “Medical “American Joint Replacement Registry Annual products might no longer be limited to Report 2019,” 2019. pharmaceuticals and medical devices. 10 I. V. Antoniac (Ed.), “Handbook of bioceramics They could also include software, appli- and biocomposites,” Springer, 2016. cations, wellness products, even health- 11 “The Prozyr Femoral Ball Recall,” All Things focused foods. The home bathroom of Biomaterials, September 23, 2017. http://allthings- the future, for example, might include a biomaterials.org/archives/170#more-170 smart toilet that uses always-on sensors 12 M. Marcolongo, S. Sarkar, and N. Ganesh, to test for nitrites, glucose, protein, and “Trends in materials for spine surgery,” Comprehensive Biomaterials II, 7: 175–98 (2017). pH to detect infections, disease, even DOI: 10.1016/B978-0-08-100691-7.00269-X Credit: Schott North America; YouTube pregnancy. A smart mirror equipped 13 D. Bray, and B. McEntire “Silicon nitride—A “The materials of the future must be smarter with facial recognition might be able to ceramic surgical implant material,” American than ever,” states a video from Schott’s Op- distinguish a mole from melanoma,” the Ceramic Society Bulletin, 99(3): 32–5 (2020). portunity lab. report says. 14 T. J. McCue, “Additive manufacturing industry The company is clearly giving top marks to Ultimately, the entire landscape of grows to almost $12 billion in 2019,” Forbes, May ultrathin glass, as the video depicts a trans- how we approach, monitor, manage, and 8, 2020. https://www.forbes.com/sites/tjmc- cue/2020/05/08/additive-manufacturing-industry- parent glass bandage being directly applied to mitigate human health is shifting. While grows-to-almost-12-billion-in-2019/#36c737545678 a cut in the skin. these changes will not come without 15 S. Geier, and I. Potestio, “3D-printing: From In this concept, thin-film sensors are inte- challenges to the market for biomateri- multi-material to functionally-graded ceramic,” grated into a small sheet of ultrathin glass, als, they also offer incredible opportu- Ceramic Applications 8: 32–4 (2020). which can be applied directly to a wound to nity—and ceramics and glass are certainly 16A. E. Jakus, “Tissue engineering and addi- not only treat the wound and help it heal but well-positioned to capitalize on such tively manufactured ceramic-based biomaterials,” also to transmit health data in real time. opportunities as well as integrate critical American Ceramic Society Bulletin, 98(4): 23–30 (2019). Although the smart bandage is a concept idea, function into the human body. n 17 it plays into current medical trends toward A. E. Jakus, A. L. Rutz, S. W. Jordan, A. connected devices and data-driven monitor- Kannan, S. M. Mitchell, C. Yun, K. D. Koube, ACKNOWLEDGEMENTS S. C. Yoo, H. E. Whiteley, C.-P. Richter, R. D. ing of health, with increasing use of sensors We thank Carolyn Primus for her Galiano, W. K. Hsu, S. R. Stock, E. L. Hsu, and R. in and on the body to continuously measure review of and detailed suggestions for N. Shah, “Hyperelastic ‘bone’: A highly versatile, diverse health parameters. the section “Ceramics used in dentistry.” growth factor–free, osteoregenerative, scalable, and Yet although thin glass is flexible, it is still surgically friendly biomaterial,” Science Translational Medicine, 8[358], 358ra127 (2016). DOI: 10.1126/ breakable—meaning that damaging this REFERENCES scitranslmed.aaf7704 bandage could result in additional wounds 1 18 ® beyond what the bandage was originally WorldoMeter, “Life expectancy of the world L. L. Hench, “The story of Bioglass ,” Journal of population.” https://www.worldometers.info/ Materials Science: Materials in Medicine, 17: 967–978 intended to treat. demographics/life-expectancy. 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