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Additive manufacturing (AM) affords the opportunity to print tailored pharmaceuticals to customize the quantity of medicine, number of medicines, and time and rate of release to be adapted for an individual's needs. A series of sulfonated poly(ethylene glycol) (SPEG) polymers for fused filament fabrication (FFF) that (i) dissolves quickly (

Additive manufacturing enables the creation of novel structures and geometries previously unattainable through traditional processing techniques. In particular, vat photopolymerization provides unprecedented resolution through the tailored delivery of light with photo-crosslinkable or photo-polymerizable materials. Traditionally, chemical crosslinks generate a permanent network, which exhibits swelling but not dissolution. In this work, photopolymerization of photo-reactive monomers with acrylate, acrylamide, and vinyl polymerizable sites enabled the formation of water-soluble 3D printed parts using vat photopolymerization. A library of monomers with varied ionic and hydrogen bonding sites provided photopolymerized films with tensile properties approaching 1200% elongation at break and 0.47 MPa stress at 100% elongation. The rate of polymerization and the subsequent mechanical properties revealed a dependence on the type of supramolecular interactions and functionality on the resulting hydrogel. The diverse functionality of the monomers enabled aqueous dissolution times ranging from 27 to 41 min. Vat photopolymerization of a trimethylammonium ethyl acrylate chloride solution and with 30 wt% N-vinyl pyrrolidone provided 3D parts with fine structural resolution. This method of creating soluble, water-swollen structures through vat photopolymerization provides future research with a larger library of monomers for diverse applications including soluble support scaffolds.

Single-walled carbon nanohorns (SWNHs) have been shown to be effective photothermal enhancers and drug delivery agents for potential cancer therapy, particularly for the eradication of bladder cancer lesions. In this study, the potential for SWNHs to serve as nanotheranostic vehicles is demonstrated through simultaneous delivery of the chemotherapeutic cisplatin from SWNH cone interiors and imaging of the nanoparticle transport to tumor cells using conjugated quantum dots (QDs). Following the formation of cisplatin-modified SWNH-QD (SWNH-QD + cis) hybrids, their characterization by scanning and transmission electron microscopy (STEM, TEM), energy dispersive spectroscopy (EDS), and dynamic light scattering (DLS) were performed to characterize the composite nanoparticles. Drug release profiles and 50% inhibitory concentration (IC50) determination showed that QDs do not hinder the therapeutic ability of SWNHs. In addition, the hybrids were trackable over the course of a 3 day period, which indicates that internalized SWNHs can continue to deliver therapy after removal of the nano-agents from the cell culture. This unique SWNH hybrid can successfully be used as an imaging agent to study nanoparticle transport and consequently the delivery of a therapeutic to the targeted cancer cells.

This research presents a rapid screening process for analyzing the extrudability of polymeric materials for filament extrusion based additive manufacturing (AM) by predicting extrusion failure. This rapid screening process can further suggest optimal Fused Filament Fabrication (FFF) processing conditions for a specific material. Annular backflow and filament buckling, which are the two primary failure modes during extrusion in FFF, are considered in this study. The screening method focuses on model analysis of annular backflow while simultaneously considering a previously developed model for filament buckling and includes the introduction of a non-dimensional number (Flow Identification Number, or FIN) that predicts a material's propensity to backflow based on a rheological analysis and the system geometry. Annular backflow was modeled by calculating velocity profiles and determining the normalized net flow magnitude. The backflow and buckling models were experimentally verified with acrylonitrile butadiene styrene, low density polyethylene, and sodium sulfonated poly(ethylene) glycol. We empirically validated that the FIN was able to accurately predict backflow and that the potential to backflow and, by extension, propensity to fail during extrusion, is most sensitive to fluctuations in filament diameter and the material's shear thinning behavior. Our results demonstrate the importance of printing in the shear thinning regime to reduce the effect of processing conditions on the extrudability of a polymer.

Due to continued health and safety concerns surrounding isocyanates, alternative synthetic routes to obtain urea-containing polymers is gaining much attention. Melt polycondensation of urea with diamines achieved polyureas in the absence of catalyst or solvents. 1H NMR spectroscopy and thermogravimetric analysis confirmed targeted compositions and thermal stability, respectively. Differential scanning calorimetry and dynamic mechanical analysis provided insight into the copolymers’ thermal and morphological behavior. A steady increase in the melting temperature across the range of compositions suggested co-crystallization of the different repeating units, in sharp contrast to non-hydrogen bonded copolymers. Furthermore, tunable melt temperatures and mechanical performance illustrated the versatility of these copolymers in high performance applications. Finally, initial biodegradation studies using a naturally occurring, soil enzyme (urease) demonstrated steady degradation over 4 weeks, releasing ammonia as a potential nitrogen source for agricultural applications.

Gynecological cancer treatment strategies commonly employ pelvic brachytherapy, a technique that temporarily locates radioactive materials in or near the source of the tumor. Despite numerous advances in brachytherapy treatment protocols, advances in the required vaginal packing materials lag significantly. This paper describes a packing material for vaginal brachytherapy based on a poly(ethylene glycol) (PEG)-based hydrogel. Commercially available oligomeric starting materials rapidly formed a hydrogel upon action of mild base (NaHCO3) through a thiol-Michael addition reaction. Tuning the base concentration enabled rapid formation of hydrogels with moduli sufficient for effective tissue displacement (>10 kPa). The poly(ethylene glycol) diacrylate oligomer molecular weight exerted minimal influence on the hydrogel modulus. The hydrogels absorbed up to four times their weight in water from the dry state. CT imaging demonstrated distinguishability between hydrogel, water, and metal medical tools. The hydrogels did not induce significant IL-8 upregulation or cytotoxicity when cultured against vaginal macrophage cells, suggesting lack of immunogenicity. Our findings support these hydrogels as ideal candidates for a packing material in pelvic brachytherapy applications.

Peptide nucleic acids (PNAs) are an emerging family of biomaterials designed to specifically target and treat diseased cells, most commonly in the antimicrobial-resistant bacteria MRSA. While PNAs offer great promise for the elimination of these bacteria, they are significantly more expensive than traditional peptides and often do not provide functionality for analysis. In this work, a model peptide (KFFCCQ) was developed to evaluate peptide coatings adhered to fibrous surfaces with multiple functional handles, i.e. the presence of a sulfur atom in cysteine and an aromatic ring in phenylalanine, to predict the durability of PNA coatings on 50/50 nylon/cotton blends (NyCo), which are commonly used in clothing such as combat and medical attire. Following elemental analysis through XPS and EDX-SEM, rinses were performed on the fabrics and the subsequent release of peptide was evaluated with UV–vis. As expected, elevated temperature and increased time resulted in higher KFFCCQ release levels from the NyCo fibers. Finally, EDX-SEM examined the presence of KFFCCQ following rinse cycles, revealing that a higher level of KFFCCQ released from nylon fibers compared to cotton fibers. This evaluation proves the utility of KFFCCQ as a preliminary model to evaluate adhesion and release of peptides from nylon and cotton fibrous surfaces.

The inherent hydrolytic reactivity of polyesters renders them excellent candidates for a variety of biomedical applications. Incorporating ionic groups further expands their potential impact, encompassing charge-dependent function such as deoxyribonucleic acid (DNA) binding, antibacterial properties, and pH-responsiveness. Catalyst-free and solvent-free polycondensation of a bromomethyl imidazolium-containing (BrMeIm) diol with neopentylglycol (NPG) and adipic acid (AA) afforded novel charged copolyesters with pendant imidazolium sites. Varying ionic content influenced thermal properties and offered a wide-range, −41 to 40 °C, of composition-dependent glass transition temperatures (Tgs). In addition to desirable melt and thermal stability, polyesters with ionic concentrations ≥15 mol % readily dispersed in water, suggesting potential as nonviral gene delivery vectors. An electrophoretic gel shift assay confirmed the novel cationic copolyesters successfully bound DNA at an N/P ratio of 4 for 50 mol % and 7...

Supramolecular chemistry continues to experience widespread growth, as fine-tuned chemical structures lead to well-defined bulk materials. Previous literature described the roles of hydrogen bonding, ionic aggregation, guest/host interactions, and π-π stacking to tune mechanical, viscoelastic, and processing performance. The versatility of reversible interactions enables the more facile manufacturing of molded parts with tailored hierarchical structures such as tissue engineered scaffolds for biological applications. Recently, supramolecular polymers and additive manufacturing processes merged to provide parts with control of the molecular, macromolecular, and feature length scales. Additive manufacturing, or 3D printing, generates customizable constructs desirable for many applications, and the introduction of supramolecular interactions will potentially increase production speed, offer a tunable surface structure for controlling cell/scaffold interactions, and impart desired mechanical properties through reinforcing interlayer adhesion and introducing gradients or self-assembled structures. This review details the synthesis and characterization of supramolecular polymers suitable for additive manufacture and biomedical applications as well as the use of supramolecular polymers in additive manufacturing for drug delivery and complex tissue scaffold formation. The effect of supramolecular assembly and its dynamic behavior offers potential for controlling the anisotropy of the printed objects with exquisite geometrical control. The potential for supramolecular polymers to generate well-defined parts, hierarchical structures, and scaffolds with gradient properties/tuned surfaces provides an avenue for developing next-generation biomedical devices and tissue scaffolds.

Water-soluble polymers as sacrificial supports for additive manufacturing (AM) facilitate complex features in printed objects. Few water-soluble polymers beyond poly(vinyl alcohol) enable material extrusion AM. In this work, charged poly(ether ester)s with tailored rheological and mechanical properties serve as novel materials for extrusion-based AM at low temperatures. Melt transesterification of poly(ethylene glycol) (PEG, 8k) and dimethyl 5-sulfoisophthalate afforded poly(ether ester)s of sufficient molecular weight to impart mechanical integrity. Quantitative ion exchange provided a library of poly(ether ester)s with varying counterions, including both monovalent and divalent cations. Dynamic mechanical and tensile analysis revealed an insignificant difference in mechanical properties for these polymers below the melting temperature, suggesting an insignificant change in final part properties. Rheological analysis, however, revealed the advantageous effect of divalent countercations (Ca2+, Mg2+, and Z...

Subfailure matrix injuries such as sprains and strains account for a considerable portion of ligament and tendon pathologies. In addition to the lack of a robust biological healing response, these types of injuries are often characterized by seriously diminished matrix biomechanics. Recent work has shown nanosized particles, such as nanocarbons and nanocellulose, to be effective in modulating cell and biological matrix responses for biomedical applications. In this article, we investigate the feasibility and effect of using high stiffness nanostructures of varying size and shape as nanofillers to mechanically reinforce damaged soft tissue matrices. To this end, nanoparticles (NPs) were characterized using atomic force microscopy and dynamic light scattering techniques. Next, we used a uniaxial tensile injury model to test connective tissue (porcine skin and tendon) biomechanical response to NP injections. After injection into damaged skin and tendon specimens, the NPs, more notably nanocarbons in skin, led to an increase in elastic moduli and yield strength. Furthermore, rat primary patella tendon fibroblast cell activity evaluated using the metabolic water soluble tetrazolium salt assay showed no cytotoxicity of the NPs studied, instead after 21 days nanocellulose-treated tenocytes exhibited significantly higher cell activity when compared with nontreated control tenocytes. Dispersion of nanocarbons injected by solution into tendon tissue was investigated through histologic studies, revealing effective dispersion and infiltration in the treated region. Such results suggest that these high modulus NPs could be used as a tool for damaged connective tissue repair.

Nanoparticle research has seen advances in many fields, including the imaging and treatment of cancer. Specifically, nanotechnology has been investigated for its potential to be used as a tool to deliver well-tested drugs in potentially safer concentrations through both passive and active tumor targeting, while additionally providing means for a secondary therapy or imaging contrast. In particular, the use of light in conjunction with nanoparticle-based imaging and therapies has grown in popularity in recent years due to advances in utilizing light energy. In this review, we will first discuss nanoparticle platforms that can be used for optical imaging of cancer, such as fluorescence generation with quantum dots and surface-enhanced Raman scattering with plasmonic nanoparticles. We then analyze nanoparticle therapies, including photothermal therapy, photodynamic therapies, and photoacoustic therapy and their differences in exploiting light for cancer treatment. For photothermal therapies in particular, we have aggregated data on key variables in gold nanoparticle treatment protocols, such as exposure energy and nanoparticle concentration, and hope to highlight the need for normalization of variable reporting across varying experimental conditions and energy sources. We additionally discuss the potential to co-deliver chemotherapeutic drugs to the tumor using nanoparticles and how light can be harnessed for multifunctional approaches to cancer therapy. Finally, current in vitro methods of testing these therapies is discussed as well as the potential to improve on clinical translatability through 3D tissue phantoms. This review is focused on presenting, for the first time, a comprehensive comparison on a wide variety of photo based nanoparticle interactions leading to novel treatments and imaging tools from a basic science to clinical aspects and future directions.

Single-walled carbon nanohorns (SWNHs) have significant potential for use in photothermal therapies due to their capability to absorb near infrared light and deposit heat. Additionally, their extensive relative surface area and volume makes them ideal drug delivery vehicles. Novel multimodal treatments are envisioned in which laser excitation can be utilized in combination with chemotherapeutic-SWNH conjugates to thermally enhance the therapeutic efficacy of the transported drug. Although mild hyperthermia (41–43 °C) has been shown to increase cellular uptake of drugs such as cisplatin (CDDP) leading to thermal enhancement, studies on the effects of hyperthermia on cisplatin loaded nanoparticles are currently limited. After using a carbodiimide chemical reaction to attach CDDP to the exterior surface of SWNHs and nitric acid to incorporate CDDP in the interior volume, we determined the effects of mild hyperthermia on the efficacy of the CDDP-SWNH conjugates. Rat bladder transitional carcinoma cells were exposed to free CDDP or one of two CDDP-SWNH conjugates in vitro at 37 °C and 42 °C with the half maximal inhibitory concentration (IC50) for each treatment. The in vitro results demonstrate that unlike free CDDP, CDDP-SWNH conjugates do not exhibit thermal enhancement at 42 °C. An increase in viability of 16% and 7% was measured when cells were exposed at 42 deg compared to 37 deg for the surface attached and volume loaded CDDP-SWNH conjugates, respectively. Flow cytometry and confocal microscopy showed a decreased uptake of CDDP-SWNH conjugates at 42 °C compared to 37 °C, revealing the importance of nanoparticle uptake on the CDDP-SWNH conjugate's efficacy, particularly when hyperthermia is used as an adjuvant, and demonstrates the effect of particle size on uptake during mild hyperthermia. The uptake and drug release studies elucidated the difference in viability seen in the drug efficacy studies at different temperatures. We speculate that the disparity in thermal enhancement efficacy observed for free drug compared to the drug SWNH conjugates is due to their intrinsic size differences and, therefore, their mode of cellular uptake: diffusion or endocytosis. These experiments indicate the importance of tuning properties of nanoparticle-drug conjugates to maximize cellular uptake to ensure thermal enhancement in nanoparticle mediated photothermal-chemotherapy treatments.

Additive manufacturing, or three-dimensional (3D) printing, has emerged as a viable technique for the production of vascularized tissue engineering scaffolds. In this report, a biocompatible and biodegradable poly(tri(ethylene glycol) adipate) dimethacrylate was synthesized and characterized for suitability in soft-tissue scaffolding applications. The polyester dimethacrylate exhibited highly efficient photocuring, hydrolyzability, and 3D printability in a custom microstereolithography system. The photocured polyester film demonstrated significantly improved cell attachment and viability as compared with controls. These results indicate promise of novel, printable polyesters for 3D patterned, vascularized soft-tissue engineering scaffolds.