Bioresorbable PLA (polylactic acid) and PGA (polyglycolic acid) resins have been used in orthopaedic applications for several decades. Initial applications for these resins included sutures and staples for wound closure and eventually extended to the internal fixation of fractures and other orthopaedic uses. Parts molded from PLA and PGA resins offer significant benefits over metallic fixation in many orthopaedic applications. The biodegradable nature of these resins eliminates the need for secondary removal of metal plates, screws, and cleats due to wear or loosening. It also significantly reduces considerations of metallic biocompatibility.

Orthopaedic devices molded of PLA and PGA resins typically conform to conventional macromolding parameters. With the exception of high sensitivity to moisture and oxygen exposure, both the mold design and processing of such parts are fairly straightforward. The desirable features of bioresorbable resins, however, have led to an expansion of applications with smaller and smaller device designs. As implantable and bioresorbable molded parts approach micro or nano sizes, even a toothpick-sized runner is still too large and too costly (bioresorbable raw material costs $3,000–$22,000/lb).

In addition, as applications have evolved toward the micro (and eventually nano) regime, these resins have presented a number of challenges in the storage, molding, and processing of bioresorbable micromolded parts. Micromolding, with its small gate sizes, creates challenges for bioresorbable PLA and PGA materials, which are highly shear sensitive and moisture sensitive. This article explores some of the challenges involved, such as shear stress through small gates, humidity control for extremely small shot sizes, and integrating macro-to-micro technologies to produce near-micron-level geometry in precision, micromolded bioresorbable components.  

Bioresorbable Applications

Figure 1 shows common applications for bioresorbable micromolded components. In this life cycle curve, most of the work being done is in the new product area, R&D developments, drug-eluting products, and implants being used as pharmaceutical carriers (see Figure 2 for examples of some specific applications). High-volume (growth) products, which are produced in the hundreds of thousands of parts annually, include bone screws, anchors, and facial implants. Bone screws typically made of titanium can be replaced with bioresorbable materials so that patients are not stuck with those bone screws for the rest of their lives. After a certain amount of time, the affected bones fuse together and no longer require screws; unlike with titanium screws, the body can absorb the resorbable material and turn it into carbon dioxide and water. It is then flushed from the human system naturally. 

The mature products segment is also a highly active area because this is the stage at which many conventional molders try to develop a workaround molding method. In the beginning, molders may put microcomponents into large mold frames and conventionally sized molding machines. However, the runners and sprues generate costly material scrap, so retooling programs  to accommodate true micromolding processes are almost always an immediate return on investment (ROI).

Mold Design

Figure 1. [click to enlarge] A life cycle curve showing common applications for bioresorbable micromolded components.

A mold design with a properly sized gate and a very small runner and sprue (if any) is critical to product quality and cost. As previously mentioned, bioresorbable raw material costs $3,000–$22,000 per pound, and even a toothpick-sized runner and sprue can add up to hundreds of thousands of dollars of scrap annually. Mold venting is also important because clogged vents prematurely degrade the polymer and cause burning of the implant during processing. 

If gates and runners are used, a micromolded part is typically easier to degate using an edge gate as opposed to a subgate. Degating methods such as ultrasonic degating, using tiny knives in a fixture, or in-mold degating are used to avoid gate vestiges as a result of subgating. If the bioresorbable implant is in direct contact with skin or arteries, even a very small gate vestige can be detrimental to the implantable application—that little piece can pierce an artery or vein. If the wall thickness allows, cutting into the part (i.e., shaving the part) is better than taking a chance on the vestige. 

Processing Challenges of Bioresorbables

There are many different compounds of PLA-PGA, with the most common being the 82/18 version (82% lactide, 18% glycolide). A very high concentration of glycolide creates material-handling and feeding difficulties due to the gooey nature of the glycolide. An abundance of information about the materials can be found through bioresorbable polymer suppliers such as Purac, Boehringer Ingelheim, SurModics, and DSM.

Figure 2. Examples of bioresorbable parts. Shown here is a bioresorbable suture artiface for internal tissue reconstruction (a), bioresorbable suture feature for internal tissue repair (b), and bioresorbable micromolded containers for targeted drug delivery (c).

The first challenge encountered by processors of bioresorbables is material handling, which is the single largest area for error. PLA-PGA materials are highly susceptible to moisture and heat. They must be stored properly (usually in a freezer) at a specified temperature in nitrogen-sealed foil pouches. They must then be used according to the material drying cycle and the processing run quantities needed. Material usage must be matched with the injection screw and shot size in an injection molding machine so that the material is not sitting in an improperly sized machine. Having the material rest in a poorly sized machine can cause overdrying and overheating due to the prolonged temperature and drying exposure.

Micromolding machines are also a key component to processing bioresorbable polymers. When it comes to this topic, however, very little information is available on the market due to proprietary processing techniques and a lack of industry-specific testing for custom compounds. Because the materials in question are highly shear and heat sensitive, it is critical to have a proper fit of the shot size for a micromolded part to the screw and barrel. The residence time (the amount of time the polymer sits in the barrel) can affect the intrinsic viscosity (IV) of the material. Small shot–sized machines are typical in the design of micromolding machines. Some of them use reciprocating screws and some use screw-over-plunger technology. In addition, some bioresorbable material processors are developing new equipment because even the smallest shot sizes available on the market are too large to properly process small amounts of bioresorbable polymers. These machines are typically proprietary and primarily used internally or through licensing agreements.

Several other challenges exist in micromolding, but there are ways to minimize these challenges and the corresponding risk of failure for component manufacturers. These challenges include the following.

Modeling of Microcomponents. There remains a limited understanding of fundamental physics at the micro scale, and these principles are necessary to develop reliable models. Perfecting the mesh is critical to obtaining the correct result in any analysis. Because microparts have such small features (and therefore very large solid model sizes), implementing painstaking processes in meshing a high-resolution model is key to an accurate analysis.   

Environment. A fraction of one single degree of temperature change can affect precision when machining (or measuring) at the submicron level. As such, many micromolders and micromachining experts enclose the entire machine or inspection area to create a controlled working environment.

Metrology and Inspection Techniques. Inspection methods for micromolded parts dictate customized vises, tweezers, and fixturing (not to mention extreme patience). Inspecting the mold steel as opposed to the actual parts is also practical because the tooling surfaces and intersections are usually flatter and crisper than the parts themselves. They are also better suited for noncontact measurement. And because the mold cavities and cores are much bigger than the parts, fixturing and contact measurement are easier. With microparts, the difference between the steel and plastic is minimal because the shrinkage factor doesn’t play much of a role.

Using these same surfaces to certify the dimensions can provide much more repeatability and reproducibility than attempting the same corresponding measurement in the micromolded components. It’s not uncommon for the first-article inspection to consume as much time if not more than the entire micromold making and micromolding project combined. One of the latest time-saving techniques in this area, however, is laser scanning of the micropart. The laser scans the component, turns it into point cloud data, and those data can then be directly file-compared to the nominal solid model to see where problem dimensions exist. 

Figure 3. Tensile bar tooling for bioresorbable resins.

Gauge repeatability and reproducibility (R&R) from client to vendor requires using duplicate fixtures and exact methods of inspection techniques to repeat the results to near-micron tolerances. Only a select few sources of inspection equipment exist that can measure to submicron tolerances. In addition, extremely clean, HEPA-filtered, air-controlled rooms are necessary environmental elements for repeatable measurements. 

It’s also common in macrocomponents, and specifically with medical devices, to insist on 1.33 Cpk or better with respect to drawing dimensions or tolerance. But achieving 1.33 Cpk on 0.0001-in. tolerances is nearly a mathematical impossibility in some cases when the gauge R&R and operator R&R are taken into account. Component manufacturers and micromolders require similar inspection machines with identical fixtures to validate tolerances in microcomponents.

Properly Sized Machines. It is common to see micromolded components that have sprue and runner systems amount to 75% or more of the total shot. For many molders trying to enter this market, micromolding parts in larger machines is commonly attempted. Molding parts in this manner is not recommended on machines larger than 0.5 oz because it is hard to control such small shot sizes. Also, long residence times and material degradation can occur with oversized screw-barrel combinations. Tabletop machines are not considered good candidates for micromolding because they are not usually designed for high-volume production and process control capability.

Part Handling. Part handling can be challenging given the sizes of micromolded components. Many micromolders use edge-gated runners to carry their parts from one location to another and many are used as part of the automation process. If parts cannot be edge-gated, micromolders often use customized end-of-arm tooling, vacuum systems, reel-to-reel take-up equipment, and blister packs.

Static. Static electricity is a micromolder’s nightmare. Parts as small as dust can easily be lost if proper grounding of part collection systems, robotics, packaging, and inspection systems are not performed. Static guns, wands, air curtains, and grounding mats are commonplace in micromolding facilities.

Materials Testing

To determine whether the bioresorbable implant is robust enough, it is important to characterize the material during many different phases in the injection molding process. For example, PLA-PGA pellets in their raw form are stored in nitrogen-sealed pouches. Opening this pouch and exposing the polymer to a small degree of temperature change and humidity starts to degrade the polymer immediately (as if it were already in the body and starting to do its job). 

Consequently, PLA-PGA compounds must be dried in nitrogen-sealed hoppers in most cases, and IVs must be validated throughout the injection molding process. Temperature rise from shear in the injection molding screw and barrel also decreases the material’s IV. Additional shear from small mold gates can also decrease the IV. Once the PLA-PGA component is molded, however, there is a protective skin around the molded part. This allows the part to be left for a small period of time outside of a nitrogen-sealed environment.

Validation

Due to the nature of bioresorbable polymers and their use in implantable devices, they are often processed in a classified cleanroom and validated using ISO 9001 and ISO 13485 quality systems. IV values should be validated throughout the molding process. Samples should be taken from the bag after the drying process and molding cycle. Test both the runner and the part to compare shear effects through the gates, after a period of time in the package, and through different temperatures for shelf life tests. This testing ensures the validity of the implant throughout its life cycle in vitro for proper form, fit, and function.

Design of Experiment Testing

By the time a 4.0-IV material is processed, rapid deterioration of polymer properties can take place. If improperly processed, the material also behaves improperly in vitro and causes an implant to resorb prematurely. There are tools available to test the effect of processing conditions on PLA-PGA materials, such as a gate shear test or tensile bar test shown in Figure 3. The gate shear test consists of eight cavities with varying wall thicknesses from 0.002 to 0.009 in. (0.05–0.23 mm), and the gate is always 75% of the wall thickness. The varying gates simulate varying shear on the PLA-PGA materials. These coupons are then tested for IV loss and simulate what happens to a particular compound before an expensive shaped mold is built using a similar gate size. The tensile bar, an ASTM standard for micromolding, can be used to test tensile properties of a given wall thickness (see Figure 3). 

Mature Products

Table I. [click to enlarge] Example of an ROI for a workaround molding method.

Mature products, which are not truly mature in time or years but mature in cost and depreciation, reach this stage when conventional injection molding methods are used to create the molded parts. This is typical when using 40–80-tn presses that require large-surface-area molds to fit in them. The material loss due to large paths in sprues and runners is extremely costly for $3,000/lb materials. These mature products provide a return on their initial investment when molders switch to equipment more appropriate for micromolding, and an even quicker return when runnerless molds are used. 

The example in Table I shows a typical ROI for what is referred to as a workaround micromolding method. About $4 million in cost savings is realized when changing from a toothpick-sized runner and sprue to a runnerless bioresorbable mold. It would take just one molding run to pay for the capital of micro runnerless tooling equipment.

Conclusion

There are critical steps required in the handling, testing, processing, and validation of bioresorbable molded components. Material characterization throughout the molding process is critical to understanding the viscosity changes of bioresorbable polymers such that when they are in the body, they will not prematurely resorb or stay too long for the implant to properly function. 

As is usually the case in micromolding, processing bioresorbable materials requires specialized equipment, design, and validation expertise. Choosing the right supplier, i.e., one that is experienced in bioresorbable processing and micro feature generation, can create a smooth path to success.

Donna Bibber is technical consultant for microPEP (East Providence, RI).