Publications by authors named "Joseph M DeSimone"

In an era marked by a growing demand for sustainable and high-performance materials, the convergence of additive manufacturing (AM), also known as 3D printing, and the thermal treatment, or pyrolysis, of polymers to form high surface area hierarchically structured carbon materials stands poised to catalyze transformative advancements across a spectrum of electrification and energy storage applications. Designing 3D printed polymers using low-cost resins specifically for conversion to high performance carbon structures via post-printing thermal treatments overcomes the challenges of 3D printing pure carbon directly due to the inability of pure carbon to be polymerized, melted, or sintered under ambient conditions. In this perspective, we outline the current state of AM methods that have been used in combination with pyrolysis to generate 3D carbon structures and highlight promising systems to explore further.

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Soft sensors that can perceive multiaxial forces, such as normal and shear, are of interest for dexterous robotic manipulation and monitoring of human performance. Typical planar fabrication techniques have substantial design constraints that often prohibit the creation of functionally compelling and complex architectures. Moreover, they often require multiple-step operations for production.

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Stereolithography enables the fabrication of three-dimensional (3D) freeform structures via light-induced polymerization. However, the accumulation of ultraviolet dose within resin trapped in negative spaces, such as microfluidic channels or voids, can result in the unintended closing, referred to as overcuring, of these negative spaces. We report the use of injection continuous liquid interface production to continuously displace resin at risk of overcuring in negative spaces created in previous layers with fresh resin to mitigate the loss of Z-axis resolution.

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Acoustic levitation is frequently used for non-contact manipulation of objects and to study the impact of microgravity on physical and biological processes. While the force field produced by sound pressure lifts particles against gravity (primary acoustic force), multiple levitating objects in the same acoustic cavity interact via forces that arise from scattered sound (secondary acoustic forces). Current experimental techniques for obtaining these force fields are not well-suited for mapping the primary force field at high spatial resolution and cannot directly measure the secondary scattering force.

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Using high-resolution 3D printing, a novel class of microneedle array patches (MAPs) is introduced, called latticed MAPs (L-MAPs). Unlike most MAPs which are composed of either solid structures or hollow needles, L-MAPs incorporate tapered struts that form hollow cells capable of trapping liquid droplets. The lattice structures can also be coated with traditional viscous coating formulations, enabling both liquid- and solid-state cargo delivery, on a single patch.

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Vat photopolymerization (VP) additive manufacturing enables fabrication of complex 3D objects by using light to selectively cure a liquid resin. Developed in the 1980s, this technique initially had few practical applications due to limitations in print speed and final part material properties. In the four decades since the inception of VP, the field has matured substantially due to simultaneous advances in light delivery, interface design, and materials chemistry.

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Particle fabrication has attracted recent attention owing to its diverse applications in bioengineering, drug and vaccine delivery, microfluidics, granular systems, self-assembly, microelectronics and abrasives. Herein we introduce a scalable, high-resolution, 3D printing technique for the fabrication of shape-specific particles based on roll-to-roll continuous liquid interface production (r2rCLIP). We demonstrate r2rCLIP using single-digit, micron-resolution optics in combination with a continuous roll of film (in lieu of a static platform), enabling the rapidly permutable fabrication and harvesting of shape-specific particles from a variety of materials and with complex geometries, including geometries not possible to achieve with advanced mould-based techniques.

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Achieving a circular plastics economy is one of our greatest environmental challenges, yet conventional mechanical recycling remains inadequate for thermoplastics and incompatible with thermosets. The next generation of plastic materials will be designed with the capacity for degradation and recycling at end-of-use. To address this opportunity in the burgeoning technologies of 3D printing and photolithography, we report a modular system for the production of degradable and recyclable thermosets photopolymerization.

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The intradermal (ID) space has been actively explored as a means for drug delivery and diagnostics that is minimally invasive. Microneedles or microneedle patches or microarray patches (MAPs) are comprised of a series of micrometer-sized projections that can painlessly puncture the skin and access the epidermal/dermal layer. MAPs have failed to reach their full potential because many of these platforms rely on dated lithographic manufacturing processes or molding processes that are not easily scalable and hinder innovative designs of MAP geometries that can be achieved.

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To date, a compromise between resolution and print speed has rendered most high-resolution additive manufacturing technologies unscalable with limited applications. By combining a reduction lens optics system for single-digit-micrometer resolution, an in-line camera system for contrast-based sharpness optimization, and continuous liquid interface production (CLIP) technology for high scalability, we introduce a single-digit-micrometer-resolution CLIP-based 3D printer that can create millimeter-scale 3D prints with single-digit-micrometer-resolution features in just a few minutes. A simulation model is developed in parallel to probe the fundamental governing principles in optics, chemical kinetics, and mass transport in the 3D printing process.

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In additive manufacturing, it is imperative to increase print speeds, use higher-viscosity resins, and print with multiple different resins simultaneously. To this end, we introduce a previously unexplored ultraviolet-based photopolymerization three-dimensional printing process. The method exploits a continuous liquid interface-the dead zone-mechanically fed with resin at elevated pressures through microfluidic channels dynamically created and integral to the growing part.

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Resolving microscopic and complex 3D polymeric structures while maintaining high print speeds in additive manufacturing has been challenging. To achieve print precision at micrometer length scales for polymeric materials, most 3D printing technologies utilize the serial voxel printing approach that has a relatively slow print speed. Here, a 30-µm-resolution continuous liquid interface production (CLIP)-based 3D printing system for printing polymeric microstructures is described.

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Vaccination is an essential public health measure for infectious disease prevention. The exposure of the immune system to vaccine formulations with the appropriate kinetics is critical for inducing protective immunity. In this work, faceted microneedle arrays were designed and fabricated utilizing a three-dimensional (3D)-printing technique called continuous liquid interface production (CLIP).

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We developed a vaccine formulation containing ApoB derived P210 peptides as autoantigens, retinoic acid (RA) as an immune enhancer, both of which were delivered using PLGA nanoparticles. The formula was used to induce an immune response in 12-week-old male mice with pre-existing atherosclerotic lesions. The nanotechnology platform PRINT was used to fabricate PLGA nanoparticles that encapsulated RA inside and adsorbed the P210 onto the particle surface.

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Atherosclerosis is a systemic chronic inflammatory disease. Many antioxidants including alpha-lipoic acid (LA), a product of lipoic acid synthase (Lias), have proven to be effective for treatment of this disease. However, the question remains whether LA regulates the immune response as a protective mechanism against atherosclerosis.

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CpG oligodeoxynucleotides are potent toll-like receptor (TLR) 9 agonists and have shown promise as anticancer agents in preclinical studies and clinical trials. Binding of CpG to TLR9 initiates a cascade of innate and adaptive immune responses, beginning with activation of dendritic cells and resulting in a range of secondary effects that include the secretion of pro-inflammatory cytokines, activation of natural killer cells, and expansion of T cell populations. Recent literature suggests that local delivery of CpG in tumors results in superior antitumor effects as compared to systemic delivery.

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Multiple studies have been published emphasizing the significant role of nanoparticle (NP) carriers in antigenic peptide-based subunit vaccines for the induction of potent humoral and cellular responses. Various design parameters of nanoparticle subunit vaccines such as linker chemistry, the proximity of antigenic peptide to NPs, and the density of antigenic peptides on the surface of NPs play an important role in antigen presentation to dendritic cells (DCs) and in subsequent induction of CD8+ T cell response. In this current study, we evaluated the role of peptide antigen proximity and density on DC uptake, antigen cross-presentation, in vitro T cell proliferation, and in vivo induction of CD8+ T cells.

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Despite efforts to develop increasingly targeted and personalized cancer therapeutics, dosing of drugs in cancer chemotherapy is limited by systemic toxic side effects. We have designed, built, and deployed porous absorbers for capturing chemotherapy drugs from the bloodstream after these drugs have had their effect on a tumor, but before they are released into the body where they can cause hazardous side effects. The support structure of the absorbers was built using 3D printing technology.

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The performance of binary electrolytes is governed by three transport properties: conductivity, salt diffusion coefficient, and transference number. Rigorous methods for measuring conductivity and the salt diffusion coefficient are well established and used routinely in the literature. The commonly used methods for measuring transference number are the steady-state current method, t, and pulsed field gradient NMR, t.

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Dengue virus (DENV) is the causative agent of dengue fever and dengue hemorrhagic shock syndrome. Dengue vaccine development is challenging because of the need to induce protection against four antigenically distinct DENV serotypes. Recent studies indicate that tetravalent DENV vaccines must induce balanced, serotype-specific neutralizing antibodies to achieve durable protective immunity against all 4 serotypes.

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Purpose: Pulmonary delivery of biologics is of great interest, as it can be used for the local treatment of respiratory diseases or as a route to systemic drug delivery. To reach the full potential of inhaled biologics, a formulation platform capable of producing high performance aerosols without altering protein native structure is required.

Methods: A formulation strategy using Particle Replication in Non-wetting Templates (PRINT) was developed to produce protein dry powders with precisely engineered particle morphology.

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Despite major advancements in cancer treatments, there are still many limitations to therapy including off-target effects, drug resistance, and control of cancer-related symptoms. There are opportunities for local drug delivery devices to intervene at various stages of cancer to provide curative and palliative benefit. Iontophoretic devices that deliver drugs locally to a region of interest have been adapted for the treatment of cancer.

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Microneedle patches, arrays of micron-scale projections that penetrate skin in a minimally invasive manner, are a promising tool for transdermally delivering therapeutic proteins. However, current microneedle fabrication techniques are limited in their ability to fabricate microneedles rapidly and with a high degree of control over microneedle design parameters. We have previously demonstrated the ability to fabricate microneedle patches with a range of compositions and geometries using the novel additive manufacturing technique Continuous Liquid Interface Production (CLIP).

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Purpose: Effective treatment of patients with locally advanced pancreatic cancer is a significant unmet clinical need. One major hurdle that exists is inadequate drug delivery due to the desmoplastic stroma and poor vascularization that is characteristic of pancreatic cancer. The local iontophoretic delivery of chemotherapies provides a novel way of improving treatment.

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