Eric Luis*, Hang Liu, Juha Song, Wai Yee Yeong
Singapore Centre for 3D Printing, School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore
*Corresponding author: Eric Luis, Singapore
Centre for 3D Printing, School of Mechanical and Aerospace Engineering, Nanyang
Technological University, N3.1-B2C-03, 50 Nanyang Avenue Singapore 639798,
Singapore. Email: G001@ntu.edu.sg, firstname.lastname@example.org
Received Date: 16 July, 2018; Accepted Date:
20 July, 2018; Published Date: 25 July, 2018
This paper discusses medical grade silicone use in the production of medical implants and devices and reviews the state-of-the-art silicone 3D printing technologies including stereolithography , moisture-cured extrusion , heat-cured extrusion, hybrid jetting and UV-extrusion  and freeform reversible embedding  including PICSIMA . The advantages and disadvantages of each method are discussed in detail and the challenges unique to silicone 3D Printing are highlighted.
Silicone resins are thermoset materials which start out in liquid form and cures irreversibly into solid state with heat. The key attributes of liquid silicone resin (LSR) which make it the ideal material of choice include its hardness, tensile strength, compression strength and fluid resistance. Medical grade silicones, in addition, are selected for their biocompatibility and bio-implantability. The benefits of medical-grade LSR over other elastomeric materials include :1) its Bio-inertness in compliance with ISO 10993, USP Class VI and RoHS standards, 2) its ability to be sterilized by a variety of methods such as Autoclave, ETO, E-beam and Gamma-radiation processes, 3) its stability over a wide range of temperatures 150 F to 450 F and 4) its ability to maintain its resilience, flexibility and capability to transfer mechanical force at extreme temperatures. Using the standard ISO 10993 which evaluates the biosafety of materials in contact with the body, medical grade silicones can be grouped into 3 categories, namely: limited exposure, prolonged exposure and permanent contact. Limited exposure products have less than 24-hour contact with skin, mucosal membranes or breached surface. Prolonged exposure products have surface contact or are implanted more than 24 hours and up to 30 days and require tests protocols for haemolysis, genotoxicity, toxicity and intramuscular implantation with histopathology. Permanent contact silicone products are implanted for more than 30 days and require test protocols for carcinogenicity, chronic toxicity and developmental toxicity.
Silicone was first used for urethral implantation in 1950 and subsequently for shunts and interphalangeal joint silicone replacement prosthesis. It was not until 1962 that silicone breast implant made its debut and its development continued through the 1990s. Unfortunately, the use of silicones for meniscus replacement in knees have not been described in literature. Typical medical application of silicones is shown in (Table 1).
Its use in silicone implants and extracorporeal equipment and devices are discussed below. Conventionally, silicone implants have been manufactured by direct or indirect molding techniques . Since 2015, only a limited number of silicone 3D Printing, also known as additive manufacturing, technologies have been introduced such as stereolithography , moisture-cured extrusion , hybrid jetting and UV-extrusion  and freeform reversible embedding . While these methods are only capable of printing industrial-grade silicones, only heat-cured extrusion technology is capable of printing medical grade silicones.
In 1946, F. Lahey first reported the use of silicone stents for bile duct repair . Subsequently, silicone has been used to encapsulate and insulate electronic cochlear implants and cardiac pacemakers . Recently, it has also been used for the production of intraocular lens, replacement of vitreous humor and restoration of the continuity of median and ulnar nerves in the forearm [8,9]. In 1962, Cronin. et al,  implanted the first pair of silicone gel-filled breast implants. Despite its approval for use by the U.S. Food and Drug Administration since 2006 , its long-term safety profile remained a major concern [16,17]. In contrast to Balk et al. which showed equivocal long-term health outcomes of silicone breast implants , Singh et al., in a 5 to 8-year follow-up, showed that these implants did not increase the risks of systemic diseases or suicidal rates when compared to saline implants . In 1968, A. Swanson developed the first interphalangeal implants for the hands and feet. These implants were shown to be safe without provoking any immunological or systemic reactions [12,20]. Subsequently in 1973, F. Mazas, et al. developed a total knee silicone prosthesis with shock absorbing capabilities . In reconstructive and plastic surgeries, silicone implants have also been used for nose and chin augmentation.
Equipment and Devices
Medical grade silicones are also used in the production of tubings and membranes of extracorporeal heart-lung bypass machines and blood oxygenators owing to its biocompatible, hemo-compatible and gas permeable properties . In 1968, W. Robb also developed silicone membranes which can be used to extract oxygen from fresh water .
6. Silicone Additive Manufacturing Technology
Conventionally, silicone parts or end-products have been manufactured by the molding process or indirect casting. Molding is, however, a major technical barrier since the molding process or mold fabrication is time consuming and expensive when only a few parts are needed. The molding process is also unable to manufacture hollow silicone parts with complex internal architectures or produce parts requiring multi-materials. The recent advent of various silicone AM technologies allow potential space for flexible applications such as components for soft robotics, wearable and custom assistive or rehabilitation devices. The current state-of-the-art technologies in silicone 3D printing are shown in the chart below. This section provides a review on the state-of-the-art AM technology for silicone printing. Current available techniques for silicone 3D printing described in literature are Freeform Reversible Embedding, Stereolithographic-ulltraviolet- (SLA-UV based vat photopolymerization), combined extrusion and ink-jetting, extrusion-based techniques in combination with UV-cured, moisture-cured and heat cured technologies. A comparison of the silicone printing features for available AM techniques is shown in (Table 2) below.
6.1. Freeform Reversible Embedding (FRE) using Carbapol 
6.1.1. The Experimental Setup for Freeform Reversible Embedding: Hinton et al. introduced this system in 2016, as shown in (Figure 1) .
The FRE Printing Process was performed using MakerBot 3D Printer with a custom designed syringe pump to extrude the PDMS ink Sylgard 184 which has been degassed in a planetary centrifugal mixer. The 3D models for printing were designed using SolidWorks CAD software. All STL files were processed by Slic3r software and sliced into 200 μm thick layers to generate G-code instruction, which was sent to the printer using Pronterface, an open source 3D printer host software suite. Before 3D printing, PDMS ink was drawn into a 10-mL plastic syringe and capped with a 400 μm-ID 0.75’ stainless steel needle tip. This extruder needle nozzle was positioned at the bottom center of the Carbapol support bath. The typical print speed is set at 20mm/s. Post-curing of the PDMS is performed for 72 h at room temperature or for 4 h in an oven at 65°C. The prints were then released from the support by immersing in PBS adopted from ).
6.1.2. The Principles of Freeform Reversible Embedding: The working principle of the system leverages on the immiscibility of the hydrophobic PDMS in the hydrophilic Carbopol support. The printing is freeform and is completed layer-by-layer. The Carbapol support fluidizes when the 3D printer needle moves through it and solidifies when PDMS is extruded within it. After printing and curing, the phosphate buffer solution is used to release the embedded PDMS prints.
6.1.3. Proof of Concept of Freeform Reversible Embedding: As a proof-of-concept, Sylgard 184 PDMS is used successfully to 3D print linear and helical filaments via continuous extrusion and cylindrical and helical tubes via layer-and-layer fabrication. These 3D printed tubes are manifold and perfusable, as shown in the (Figure 2) below.
6.2. Hybrid UV-Extrusion and Ink-Jetting Technique 
6.2.1. The Experimental Setup of the Hybrid UV-Extrusion and Ink-Jetting system: The hybrid system, as shown in (Figure 3), consists of three piezoelectric-pneumatic material jetting printheads, one solenoid-actuated material extrusion printhead, one pneumatic material extrusion printhead and a UV lamp.
Three controlling units sits on a 3-axis motion stage to actuate the piezoelectric stacks by sending out the voltage signals, and one controller coordinates the air-pressure in the extrusion-based printheads. The Slic3r software creates the toolpaths for the multiple nozzles. The UV-curable silicone used contains the photoinitiator, 2-Hydroxy-2-methyl propiophenone and has a dual UV/moisture curing mechanism. The polymerization process completes within a few seconds after the UV exposure with 365 nm wavelength. The full mechanical properties are achieved after exposure to the environmental moisture for 7 days.
6.2.2. The Principles of the Piezoelectric-pneumatic material jetting AM in the Hybrid system: The conventional material jetting system, formerly known as inkjet printing, is compatible with fluid shaving a maximum viscosity of 40 mPa.s. In these systems, fluids with an Ohnesorge number (
Figure 1: Experimental testbed of FRE using Carbapol (a) 3D Printing of hydrophobic PDMS prepolymer resins within a hydrophilic Carbopol gel support. Carbopol maintains the dimensional stability of the PDMS prepolymer within the support for up to 72 hours. (adopted from )