Additive manufacturing processes such as 3D printing use time-consuming, stepwise layer-by-layer approaches to object fabrication. We demonstrate the continuous generation of monolithic polymeric parts up to tens of centimeters in size with feature resolution below 100 micrometers. Continuous liquid interface production is achieved with an oxygen-permeable window below the ultraviolet image projection plane, which creates a "dead zone" (persistent liquid interface) where photopolymerization is inhibited between the window and the polymerizing part. We delineate critical control parameters and show that complex solid parts can be drawn out of the resin at rates of hundreds of millimeters per hour. These print speeds allow parts to be produced in minutes instead of hours.

Despite the increasing popularity of 3D printing, also known as additive manufacturing (AM), the technique has not developed beyond the realm of rapid prototyping. This confinement of the field can be attributed to the inherent flaws of layer-by-layer printing and, in particular, anisotropic mechanical properties that depend on print direction, visible by the staircasing surface finish effect. Continuous liquid interface production (CLIP) is an alternative approach to AM that capitalizes on the fundamental principle of oxygen-inhibited photopolymerization to generate a continual liquid interface of uncured resin between the growing part and the exposure window. This interface eliminates the necessity of an iterative layer-by-layer process, allowing for continuous production. Herein we report the advantages of continuous production, specifically the fabrication of layerless parts. These advantages enable the fabrication of large overhangs without the use of supports, reduction of the staircasing effect without compromising fabrication time, and isotropic mechanical properties. Combined, these advantages result in multiple indicators of layerless and monolithic fabrication using CLIP technology.stereolithogaphy | continuous liquid interface production | 3D printing | additive manufacturing | isotropic properties Additive manufacturing (AM), or 3D printing, is a growing field that employs the selective layering of material to build a part, which has distinct advantages compared with subtractive manufacturing (1). The benefits of additive over subtractive manufacturing are numerous and include unlimited design space, freedom of complex geometries, and reduction of waste by-products (2). Significant advancements were made to AM in the 1980s with the development of the stereolithography (SL) apparatus, a platform that uses the exposure of a rastering UV laser to selectively solidify a resin through a photopolymerization process in a top-down manner (3). The method has since been modified to solidify in a bottom-up process through the use of a digital light projection (DLP) chip that eliminates the rastering laser. The process of bottomup SL begins with a computer-aided design (CAD) file that is then converted into a series of 2D renderings using a method called "slicing" (Fig. 1A). The original object is then reconstructed in a layer-by-layer manner by reproducing these 2D renderings, one slice at a time. This process is done iteratively whereby a photoactive resin is selectively exposed to UV light through a transparent substrate, allowing for selective photopolymerization corresponding to a specific slice shape (4). Once the slice has been exposed, a series of mechanical steps of separation, recoating, and repositioning follow (Fig. 1B) to allow for subsequent exposure.The polymeric materials used in the SL process are known to have intrinsic properties that are a function of the chemical structure, molecular weight, and topology (3). Printed part properties differ from intrinsic polymeric properties because they a...

Mass customization along with the ability to generate designs using medical imaging data makes 3D printing an attractive method for the fabrication of patient-tailored drug and medical devices. Herein we describe the application of Continuous Liquid Interface Production (CLIP) as a method to fabricate biocompatible and drug-loaded devices with controlled release properties, using liquid resins containing active pharmaceutical ingredients (API). In this work, we characterize how the release kinetics of a model small molecule, rhodamine B-base (RhB), are affected by device geometry, network crosslink density, and the polymer composition of polycaprolactone- and poly (ethylene glycol)-based networks. To demonstrate the applicability of using API-loaded liquid resins with CLIP, the UV stability was evaluated for a panel of clinically-relevant small molecule drugs. Finally, select formulations were tested for biocompatibility, degradation and encapsulation of docetaxel (DTXL) and dexamethasone-acetate (DexAc). Formulations were shown to be biocompatible over the course of 175 days of in vitro degradation and the clinically-relevant drugs could be encapsulated and released in a controlled fashion. This study reveals the potential of the CLIP manufacturing platform to serve as a method for the fabrication of patient-specific medical and drug-delivery devices for personalized medicine.

We prepared nonflammable liquid polymer electrolytes for lithium-ion batteries by mixing ethoxylated perfluoropolyethers (PFPEs) with LiN(SO 2 CF 3) 2 salt. Interestingly, we identified the presence of chain coupling in the PFPE polymers and their functionalized derivatives, resulting in a mixture of PFPEs with varying molecular weights. The distribution of molecular weights, along with PFPE's multiple functionalities, allows systematic manipulation of structure to enhance electrochemical and physical properties. Furthermore, the electrolytes exhibited a wide thermal stability window (5% degradation temperature > 180°C). Despite substantial increases in viscosity upon loading the PFPEs with lithium salt, the conductivity (σ≈5x10-5 S cm-1 at 28°C) of the novel electrolytes was about an order of magnitude higher than that of our previously reported PFPE electrolytes. Ethoxylated derivatives of PFPE electrolytes exhibit elevated conductivity compared to non-ethoxylated derivatives, demonstrating our capability to enhance the conductive properties of the PFPE platform by attaching various functional groups to the polymer backbone.

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Intravaginal rings (IVRs) represent a sustained‐release approach to drug delivery and have long been used and investigated for hormones and microbicides delivery. For decades, IVRs have been manufactured by injection molding and hot‐melt extrusion with very limited design and material capabilities. Additive manufacturing (AM), specifically digital light synthesis (DLS), represents an opportunity to harness the freedom of design to expand control and tunability of drug release properties from IVRs. A novel approach to IVR design and manufacturing is reported that results in geometrically complex internal architectures through the incorporation of distinct unit cells using computationally aided design (CAD) software. A systematic approach is developed to design through the generation of an IVR library and the effects of these parameters are investigated on ring properties. The ability to precisely and predictably control the compressive properties of the IVR independent of the internal architecture with which control of drug release kinetics can be achieved is demonstrated, thus opening the door for a “plug‐and‐play” platform approach to IVR fabrication.

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OBJECTIVES/SPECIFIC AIMS: The study aims to develop and test a biocompatible 3D-printed IVRs for the mechanical and release properties of a model drug, β-estradiol, then translate these methods to the target drug, progesterone. The goals include demonstrating decoupling of mechanical and release properties of the rings, release profiles driven by geometry and efficacy in sheep animal models to evaluate device safety. METHODS/STUDY POPULATION: A novel 3D-printing platform, continuous liquid interface production (CLIP), pioneered by Carbon, enables the fabrication of complex designs on a timescale that is amenable to manufacturing. The process utilizes computational-aided design (CAD), specifying shape and geometry, which is recreated via a photopolymerization process. IVRs are fabricated with CLIP using a biocompatible resin at a rate of approximately 15 min. per ring. Rings were fabricated and assessed for the release of a model drug, β-estradiol. The process was then translated to the target drug, progesterone. Rings were evaluated for radial compression and in vitro release in simulated vaginal fluid (SVF). RESULTS/ANTICIPATED RESULTS: Intravaginal rings (IVRs) were designed and fabricated to be geometrically complex in an effort to control release. Ring geometry and subsequent pore size was achieved through the use of unit cells. Several design parameters were explored including unit cell type, size, and band presence in two resins of differing mechanical properties. Through design, a wide range of radial compressive properties were achieved which spanned values covered by commercially available rings. The release of β-estradiol in SVF was found to span 57 – 115 days and resulted in near or complete release of the total loaded drug. Changing the internal geometric design of the ring was found to have minimal influence on the compression properties, thus the mechanical and release characteristics of the rings were largely decoupled. DISCUSSION/SIGNIFICANCE OF IMPACT: This is a novel approach to the design and fabrication of intravaginal rings for the treatment of infertility. The use of CAD and the decoupling of release from mechanical properties allows for us to move away from the one-size one-dose fits all approach to IVRs.