Although we’ve heard a lot about the promise of additive manufacturing (AM), the reality is that this technology has not yet caused a revolution in medical device manufacturing. But there is a slowly forming niche of AM medical devices that relies on the combination of advanced design, processing, and innovative materials to create customized solutions.
Most hearing aids, such as those made by Sonova, are patient matched and produced using AM technologies. Cranio-facial plates that are patient matched, such as those marketed by Oxford Performance, are also notable. At the same time, serial manufacture of multi-sized products is also growing, for example, EndoLIF On-Cage and EIT Cervical Implant fusion cages marketed by Joimax and Emerging Implant Technologies, respectively.
While there are, in total, about 100 additively manufactured medical devices cleared or approved by FDA, there are only three notable devices, and two having received 510(k) clearance, that are made from bioresorbable polymers (see Table 1). These three devices all use polycaprolactone as the bioresorbable element. This material can be limiting, however, due to low melting temperature (60 °C) and extended degradation time (>3 years). Additive manufacturing technologies have significant promise for preparing custom implants and tissue scaffolding, and the number of marketed bioresorbable products is surprisingly low.
Bioresorbable polymer implants are designed to serve a temporary function. Primarily, they are polyester materials that degrade in the presence of water. This degradation breaks the polymer into shorter and shorter segments, which at some point become soluble and metabolized through natural pathways, i.e., the Krebs cycle. For example, a polylactide polymer degrades over the course of several months to years, eventually breaking down into lactic acid, while a polyglycolide polymer degrades over the course of weeks and degrades into glycolic acid. These polymers have been used in medical implants since Davis & Geck (now Medtronic) introduced Dexon®, a polyglycolide suture, in 1972.
Bioresorbable polymers are primarily thermoplastic materials that are processed using traditional manufacturing techniques such as melt extrusion and injection molding. It is common to design copolymers to customize mechanical and degradation performance, and varying the polymer chemistry has a significant impact of physical and degradation characteristics, ranging in tensile modulus from about 1,000 Pa to 1 GPa and implant duration on the order of 1 week to several years. This modularity in polymer design has enabled numerous products and has proven capable in supporting tissue repair, removing the need for retrieval surgeries, and subsequently benefiting patient quality of life.
Ideally, combining material advantages of bioresorbable polymers with an AM process that can easily create complex implants that can support tissue integration is a significant advance in patient care. But additive manufacturing hasn’t lived up to the hype … yet. So, what is holding back AM applications in bioresorbable medical devices?
Four Pillars Support Additive Manufacturing
Additive manufacturing for medical products is only possible with the combination of four pillars: software, hardware, regulation/standardization, and materials. With recent advances in software, hardware, and regulation, the reasons for slow adoption are quickly disappearing.
Software. The collection of digital resources enables image capture, part design, and motion control, which ultimately creates a series of commands that controls the printer. For custom implants, this includes CT and other imaging systems that can create a digital reconstruction of the patients own anatomy. Current technology can generate patient images with resolution down to the micrometer level, and the ability to differentiate tissues is improving. At the same time, solid modeling software is concurrently more powerful and easier to use. Most engineers and designers are now native to solid modeling concepts. Software is clearly an asset and requirement for additive manufacturing and has never been in a better position to support manufacturing.
Once a part shape is generated, the process of translation to machine commands is performed using, most often, a different piece of software. There are multiple solutions for this, with a variety of capability and quality. Current software developments are improving optimized tool paths, simultaneously saving material, improving print quality, and shortening manufacturing times.
Hardware. Hardware encompasses the equipment used to convert raw materials into a finished printed part. This is more than just a printer, as there are universal requirements for post-processing and/or cleaning after a part is printed.
The current proliferation of printer manufacturers has created significant pricing competition, bringing down the entry cost. Inexpensive desktop models for just about all but laser sintering technologies are readily available, but there do exist truly capable manufacturing-ready industrial printers.
For manufacturing with absorbable polymers, the three most common AM processes are possibly, with varying availability: fused filament fabrication (FFF), selective laser sintering (SLS), and stereolithography (SLA). FFF, because it relies on processing thermoplastic filaments in a manner not that far removed from typical melt-processing operations, has the widest material availability. Compared with other AM operations, FFF is somewhat limited by feature size and layer thickness. SLS is used to manufacture the TRS Cranial Bone Void Filler and can make parts with complex internal lattice geometries. Materials, however, are currently limited to polycaprolactone and polylactide because the laser sintering process can damage sensitive bioresorbable materials. SLA and its variants are also a capable process, and there are several bioresorbable materials in development to support product manufacturing. As with SLS, the lack of variation in bioresorbable materials is a current limitation for SLA technologies.
Regulation. Regulators, e.g., FDA, and standards organizations, e.g., ISO and ASTM, have shown that they are game to support AM technologies. FDA has recently updated its guidance about the use of AM process, where it is clear that the agency views additive manufacturing as a manufacturing process.
Standards organizations are also working to advance the use of additive manufacturing. The International Organization for Standardization (ISO) has released seven standards, with 14 more in development. ASTM is actively developing additional materials standards, as well as developing a proficiency testing program. And other organizations such as America Makes are creating frameworks through which additive manufacturing technologies can be more readily adopted.
In all cases, guidance and standardization are supportive of the ultimate goal: manufacturing medical devices that consistently meet requirements of safety, repeatability, and efficacy.
Materials. Of the four pillars, materials development is the least advanced, and this is no different for bioresorbable polymers. For the most part, materials used for AM techniques are the same materials that have been used in filament extrusion and injection molding. While this is a good place to start, shape forming by additive manufacturing is performed sequentially in small volumes (voxels) over a very short time. Peculiarities with these processes mean that many material performance features that benefit traditional manufacturing limit utility of standard materials. Of course, this specialization in material design is common for traditional processes — there are more than 30 types of polyethylene terephthalate (PET), each tailored specifically for multifilament, blown film, injection molding, cast film, and other processes.
To support development of AM products, materials specifically suited for AM processes are needed. FFF, for example, benefits from materials with rapid melting, high melt viscosity, slow quench, and low shrinkage. One of the most common FFF materials, polylactic acid (PLA), is a bioresorbable polymer and available from several sources, but is not suitable for most products because it generates relatively brittle parts and exhibits poor layer adhesion.
Several products are now promoted as medical grade, typically through the availability of USP Class VI biocompatibility assays. Sourcing control is important because few of these are made by companies focused on medical manufacturing, meaning the company may focus on higher volume commercial applications and miss key requirements for the medical supply chain. This issue is exaggerated with the case of bioresorbable products, which are almost universally used in implant applications. For these materials, supplier stability, change controls, material performance, and consistency are required to maintain the lowest risk profile.
How Are New Materials Enabling Additive Manufacturing?
Materials are currently a limitation in additive manufacturing of bioresorbable medical devices, and new developments are improving the capability of these materials. The most common concern with additive manufacturing of medical devices relates to mechanical integrity, particularly in the z-height direction (see Figure 1). One way to analyze the print strength of a part is to divide the z-height strength by the strength in the plane direction (either x- or y-) to create a “Z-height/Plane Strength Ratio.” PLA, a common bioresorbable AM material, is substantially anisotropic with build direction strength as low as 16 percent of the build plane strength (see Table 2). Lactoflex® 7415, a new AM filament, however, improves upon uniformity of mechanical performance and in one study showed ratio of build direction of up to 90 percent to build plane strength.
Many proposed applications of bioresorbable polymers relate to hard or soft tissue scaffolding, where the AM part provides a temporary structure that supports incorporation and regrowth of native tissue. Because these implants are intended to act in this way, the materials not only have a mechanical requirement, but must also support tissue ingrowth, support cellular proliferation, and degrade into byproducts that do not damage the surrounding tissue. Many applications benefit from materials with high compliance (low modulus), whereas polylactide exhibits low compliance. Copolymer solutions, such as Strataprene® (Poly-Med, Inc.), can achieve up to 100 times reduced modulus compared with polylactide.
Device architecture on a cellular level has also recently been enabled. FFF, SLA, and SLS techniques are all limited by the voxel size, typically on the order of 50–200 μm (see Figure 2). Several researchers have applied porogen techniques to create small features within a printed scaffold, which may be suitable for improved cell ingrowth or provide areas for incorporation of active pharmaceutical ingredients.
Additive manufacturing is supported by four pillars, and with recent improvements in materials the ability for creating functional products has improved. Advances in software and hardware and clarity in regulations have reduced the overall risk for developing products that rely on additive manufacturing. While these advances garner significant attention, additive manufacturing is enabled with improved materials. This is certainly the case with bioresorbable devices, a device class that could particularly benefit from additive manufacturing. New material developments, specifically designed for use in additive manufacturing, are now available to support these advanced products. With a fully supported foundation, including bioresorbable materials designed for use in these processes, additive manufacturing is finally ready to live up to its potential.
This article was written by Scott Taylor, PhD, chief technology officer at Poly-Med, Anderson, SC. For more information, Click Here .