In Situ Cured Silicone Could Enable Personalized Implants
An innovative new packaging solution for in situ curable liquid silicone rubber (LSR) features a double-cartridge prefilled dispensing system that’s designed specifically to allow sterilization of uncured medical-grade LSRs.
Medical-grade silicone is a highly valued, versatile biomaterial widely used for medical implants. Often associated with applications such as cardiovascular pacemakers, cochlear implants, hydrocephalus shunts, implantable infusion pumps, and even intraocular lenses, silicones began to be used for a broad range of orthopedic medical applications beginning in the 1960s. The idea of replacing the small joints of the hand with silicone implants was first introduced by Swanson about 50 years ago.1Since then, medical-grade silicone elastomer implants have become common in the replacement of diseased small joints. Typically, silicone elastomers are used to fabricate components of devices or entire devices, which are then assembled, packaged, and sterilized prior to implantation via surgery. Now, new dispensing technology serves as a means to provide an alternate method of surgical implantation, where uncured pre-sterilized silicone can be provided as a part of the surgical kit and cured in situ during the orthopedic procedure.
Medical-grade silicone is a highly valued, versatile biomaterial widely used throughout the body.
Benefits and Innovation
Silicone provides a diverse range of characteristics that make it useful, with properties ranging from very sticky to very slippery, and from soft and pliable to stiff or rigid. Consequently, it is very attractive for different medical uses, such as molded parts or lubricious coatings for medical devices; soft silicone adhesives for wound care; soft tissue implants; and even high-modulus tubing.
Device manufacturers often choose silicone for its established pedigree of biocompatibility, unique physical properties, and its ability to be altered at the polymer level. This ability to let manufacturers custom-modify material properties to satisfy specific medical device requirements has given silicone a reputation as a high-technology biomaterial that invites innovation.
Innovation in silicones, however, is expanding beyond the properties of the biomaterial itself. A new development in sterilizable dispensing systems allows sterile, uncured silicone elastomers to be considered for therapeutic use in orthopedic and other applications where pre-formed silicone implants are traditionally used. By enabling the silicone to be cured to its final form in situ within the specific area in the body receiving the implant, new approaches to orthopedic device design, fabrication, and implantation have the potential to be developed.
Medical-Grade Silicones: Value for Implantable Devices
To explore the value of in situ cured silicone elastomers in orthopedic applications, it’s helpful to examine some key traits and performance considerations that make silicone particularly appealing for implants.
Biocompatibility: Medical-grade silicones have been proven to be chemically stable for use in long-term implantable devices, with results demonstrating that biocompatible silicones are not harmful to living tissue.
The biomaterials supply crisis of the early 1990s presented a significant testing and documentation challenge for medical device manufacturers. There was a need to provide exhaustive safety data to obtain the regulatory approval required to market their products. Silicone especially, as the primary material from which breast implants are made, received intense evaluation. As a result, more than two decades of laboratory and clinical research and experience with silicone-containing medical devices of all types has produced thousands of peer-reviewed articles, as well as carefully considered regulatory decisions. These findings validate the safety and biocompatibility of implantable devices manufactured with silicone.
Customization: Silicone-based implanted orthopedic devices have multiple therapeutic applications, whether for finger joints or even spinal repair. Depending upon how it is used, each device has unique physical property requirements, such as firmness, cushioning ability, or flexibility. The advantage of silicone is its ability to be highly customized, so the desired properties such as elasticity, fatigue resistance, and durometer can be formulated for the appropriate functionality in a device.
Durability: Cured silicone retains its properties over long periods of time. This is especially useful in applications such as finger joint replacement, where the elasticity of the moving joint is a key characteristic. In long-term implantable applications, whatever balance of elasticity or firmness the device manufacturer specifies needs to be sustained over the life of the implant.
Curability: To fully leverage the properties of silicone, the material must be cured to activate these properties and make the material chemically stable. A widely used method for curing silicone is platinum-catalyzed addition cure. With this method, a platinum-based catalyst is included in the silicone formulation to activate crosslinking. Depending upon the final application, the silicone can cure to be relatively flexible or very hard. Platinum-catalyzed, addition cure chemistry is frequently chosen for implanted medical devices because there are no catalyzation byproducts; all formulation components are chemically bonded in the polymer matrix. Another benefit is the platinum catalyzation allows for flexibility in controlling the cure rate over a wide range of time and temperature.
Benefits of In Situ Cured Silicones in Orthopedics
The distinctive features of silicone offer tremendous potential value for therapeutic orthopedic applications. For example, they can create a seal, fill a void, provide cushioning, or enable flexibility. These types of applications can perform best when they fit the anatomy of a patient.
Until recently, silicone orthopedic devices were typically produced, cured, and sterilized prior to surgical implantation. However, the advent of silicone that can be cured in situ at the site of the implant is appealing for several reasons. In situ curing of medical-grade silicones in the body, rather than fabricating the device outside the body and implanting it, increases the ability to customize the fit of implanted orthopedic devices, since it is more of a “real-time” implant. In fact, research has already been conducted on the use of in situ-cured silicones in spinal applications. In vertebral repair, for example, it is conceivable that in situ-cured silicone could enable a custom-fit device. Using in situ-cured silicone implants also opens possibilities for less invasive implantation procedures. In addition, customization of in situ-cured silicone enables the material properties to be “tuned” in accordance with specific therapeutic requirements. For example, viscosity can be defined to make in situ implantation and curing easier to accomplish. The cure time can be tuned, so that the silicone cures in situ at body temperature. Moreover, the final physical properties of the material can be precisely defined to provide the desired performance, such as a specific level of hardness, if the orthopedic application is to support; or softness, if the orthopedic device is meant to cushion.
Sterilizing Silicone for Implants
As the industry reviews the potential for versatility and usefulness of in situ-cured silicone materials for orthopedic implants, another key factor to consider is sterilization. In order to be implanted, devices pre-fabricated with medical-grade silicones must be sterilized—so an efficient and fully verifiable sterilization solution is necessary.
The traditional method for producing silicone orthopedic devices uses a multi-step process. Although methods vary between manufacturers, most implants are molded from liquid silicone, which is then cured. This cured, molded part is typically placed along with other devices used for a specific therapeutic application into a single package or tray, which is then sealed and sterilized before it is delivered for use with a patient.
A number of processes can be used to sterilize uncured silicone. However, these processes have had challenges in the past with sterilization of platinum-catalyzed, addition cure silicones in their uncured state.
- Gamma and electron-beam irradiation: May cause premature cure
- Dry heat and autoclave: May be detrimental for heat- or moisture-sensitive formulation ingredients and packaging components
Exposing the silicone to ethylene oxide (EtO) gas is a widely used and effective sterilization method when used with compatible packaging to allow for ingress and egress of the sterilant gas. The implant is typically packaged along with the other components in the orthopedic surgical kit and sterilized as a single unit.
This process works for implants that are fabricated and cured prior to implantation. However, a technical challenge often faced by silicone manufacturers is how to package uncured silicones, so they can be sterilized then later used for in situ-cured therapeutic treatments.
New Packaging Enables Sterilization
Designed specifically to allow sterilization of uncured medical grade silicones, a new innovation in silicone dispensing systems makes in situ-cured silicone implants for orthopedics possible.
This novel, patented system2 features a dual-cartridge prefilled dispensing system. One cartridge contains the uncured silicone while the other contains the catalyzing agent. Each cartridge has a gas-permeable plunger seal that allows EtO sterilant gas to permeate through the plunger seal to sterilize the contents of the cartridge.
Key features of the packaging system include:
- Disposable syringes that are available in a variety of sizes—5.0, 10, 25, 50, and 75 mL—which offers choices to help match the needs for the specific quantity of material required
- One-step sterilization of both the material in the cartridge and the packaging
- Easily adaptable to a variety of injection technologies
- Engineered for use in complete surgical kits
Testing of this two-part dispensing system demonstrated that, after sterilization, the uncured silicones were fully sterilized, and there was no residual EtO remaining in the material. Equally important, there was minimal change to key silicone physical properties, such as rheology, durometer, modulus, work time, and cure rate.
Thus, the highly valued material properties of silicone—and the increased versatility and custom-fit capabilities offered by in situ curing of silicone—are now more viable through a dispensing system that can be efficiently and effectively sterilized prior to the orthopedic procedure.
The development of a new patented dual-cartridge prefilled silicone dispensing system makes in situ silicone curing a practical reality, offering the orthopedic community the potential to explore new therapeutic approaches that provide better outcomes to meet the implant needs of patients.