Synergistic Effect of Physical and Chemical Cross-Linkers Enhances Shape Fidelity and Mechanical Properties of 3D Printable Low-Modulus Polyesters.

Three-dimensional (3D) printing is becoming increasingly prevalent in tissue engineering, driving the demand for low-modulus, high-performance, biodegradable, and biocompatible polymers. Extrusion-based direct-write (EDW) 3D printing enables printing and customization of low-modulus materials, ranging from cell-free printing to cell-laden bioinks that closely resemble natural tissue. While EDW holds promise, the requirement for soft materials with excellent printability and shape fidelity postprinting remains unmet. The development of new synthetic materials for 3D printing applications has been relatively slow, and only a small polymer library is available for tissue engineering applications. Furthermore, most of these polymers require high temperature (FDM) or additives and solvents (DLP/SLA) to enable printability. In this study, we present low-modulus 3D printable polyester inks that enable low-temperature printing without the need for solvents or additives. To maintain shape fidelity, we incorporate physical and chemical cross-linkers. These 3D printable polyester inks contain pendant amide groups as the physical cross-linker and coumarin pendant groups as the photochemical cross-linker. Molecular dynamics simulations further confirm the presence of physical interactions between different pendants, including hydrogen bonding and hydrophobic interactions. The combination of the two types of cross-linkers enhances the zero-shear viscosity and hence provides good printability and shape fidelity.

Multiphasic Coacervates Assembled by Hydrogen Bonding and Hydrophobic Interactions.

Coacervation has emerged as a prevalent mechanism to compartmentalize biomolecules in living cells. Synthetic coacervates help in understanding the assembly process and mimic the functions of biological coacervates as simplified artificial systems. Though the molecular mechanism and mesoscopic properties of coacervates formed from charged coacervates have been well investigated, the details of the assembly and stabilization of nonionic coacervates remain largely unknown. Here, we describe a library of coacervate-forming polyesteramides and show that the water-tertiary amide bridging hydrogen bonds and hydrophobic interactions stabilize these nonionic, single-component coacervates. Analogous to intracellular biological coacervates, these coacervates exhibit "liquid-like" features with low viscosity and low interfacial energy, and form coacervates with as few as five repeating units. By controlling the temperature and engineering the molar ratio between hydrophobic interaction sites and bridging hydrogen bonding sites, we demonstrate the tuneability of the viscosity and interfacial tension of polyesteramide-based coacervates. Taking advantage of the differences in the mesoscopic properties of these nonionic coacervates, we engineered multiphasic coacervates with core-shell architectures similar to those of intracellular biological coacervates, such as nucleoli and stress granule-p-body complexes. The multiphasic structures produced from these synthetic nonionic polyesteramide coacervates may serve as a valuable tool for investigating physicochemical principles deployed by living cells to spatiotemporally control cargo partitioning, biochemical reaction rates, and interorganellar signal transport.

Accelerated in vitro oxidative degradation testing of polypropylene surgical mesh.

Polypropylene (PP) surgical mesh had reasonable success in repair of hernia and treatment of stress urinary incontinence (SUI); however, their use for the repair of pelvic organ prolapse (POP) resulted in highly variable results with lifelong complications in some patients. One of several factors that could be associated with mesh-related POP complications is changes in the properties of the implanted surgical mesh due to oxidative degradation of PP in vivo. Currently, there are no standardized in vitro bench testing methods available for assessing the susceptibility to oxidative degradation and estimating long-term in vivo stability of surgical mesh. In this work, we adapted a previously reported automated reactive accelerated aging (aRAA) system, which uses elevated temperatures and high concentrations of hydrogen peroxide (H2 O2 ), for accelerated bench-top oxidative degradation testing of PP surgical mesh. Since H2 O2 is highly unstable at elevated temperatures and for prolonged periods, the aRAA system involves a feedback loop based on electrochemical detection methods to maintain consistent H2 O2 concentration in test solutions. Four PP mesh samples with varying mesh knit designs, filament diameter, weight, and % porosity, were selected for testing using aRAA up to 4 weeks and characterized using thermal analysis, Fourier-transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR) and scanning electron microscopy (SEM). Additionally, the oxidation index (OI) values were calculated based on the FTIR-ATR spectra to estimate the oxidative degradation and oxidation reaction kinetics of PP surgical mesh. The OI values and surface damage in the form of surface flaking, peeling, and formation of transverse cracks increased with aRAA aging time. The aRAA test method introduced here could be used to standardize the assessment of long-term stability of surgical mesh and may also be adopted for accelerated oxidative degradation testing of other polymer-based medical devices.

Fabrication and Bioactivity of Peptide-Conjugated Biomaterial Tissue Engineering Constructs.

Tissue engineering combines materials engineering, cells and biochemical factors to improve, restore or replace various types of biological tissues. A nearly limitless combination of these strategies can be combined, providing a means to augment the function of a number of biological tissues such as skin tissue, neural tissue, bones, and cartilage. Compounds such as small molecule therapeutics, proteins, and even living cells have been incorporated into tissue engineering constructs to influence biological processes at the site of implantation. Peptides have been conjugated to tissue engineering constructs to circumvent limitations associated with conjugation of proteins or incorporation of cells. This review highlights various contemporary examples in which peptide conjugation is used to overcome the disadvantages associated with the inclusion of other bioactive compounds. This review covers several peptides that are commonly used in the literature as well as those that do not appear as frequently to provide a broad scope of the utility of the peptide conjugation technique for designing constructs capable of influencing the repair and regeneration of various bodily tissues. Additionally, a brief description of the construct fabrication techniques encountered in the covered examples and their advantages in various tissue engineering applications is provided.

Design principles for creating synthetic underwater adhesives.

Water and adhesives have a conflicting relationship as demonstrated by the failure of most man-made adhesives in underwater environments. However, living creatures routinely adhere to substrates underwater. For example, sandcastle worms create protective reefs underwater by secreting a cocktail of protein glue that binds mineral particles together, and mussels attach themselves to rocks near tide-swept sea shores using byssal threads formed from their extracellular secretions. Over the past few decades, the physicochemical examination of biological underwater adhesives has begun to decipher the mysteries behind underwater adhesion. These naturally occurring adhesives have inspired the creation of several synthetic materials that can stick underwater - a task that was once thought to be "impossible". This review provides a comprehensive overview of the progress in the science of underwater adhesion over the past few decades. In this review, we introduce the basic thermodynamics processes and kinetic parameters involved in adhesion. Second, we describe the challenges brought by water when adhering underwater. Third, we explore the adhesive mechanisms showcased by mussels and sandcastle worms to overcome the challenges brought by water. We then present a detailed review of synthetic underwater adhesives that have been reported to date. Finally, we discuss some potential applications of underwater adhesives and the current challenges in the field by using a tandem analysis of the reported chemical structures and their adhesive strength. This review is aimed to inspire and facilitate the design of novel synthetic underwater adhesives, that will, in turn expand our understanding of the physical and chemical parameters that influence underwater adhesion.

Synergism between Rifampicin and Cationic Polyurethanes Overcomes Intrinsic Resistance of Escherichia coli.

Antibiotic-resistant Gram-negative bacteria are emergent pathogens, causing millions of infections worldwide. While there are several classes of antibiotics that are effective against Gram-positive bacteria, the outer membrane (OM) of Gram-negative bacteria excludes high-molecular-weight hydrophobic antibiotics, making these species intrinsically resistant to several classes of antibiotics, including polyketides, aminocoumarins, and macrolides. The overuse of antibiotics such as ß-lactams has also promoted the spread of resistance genes throughout Gram-negative bacteria, including the production of extended spectrum ß-lactamases (ESBLs). The combination of innate and acquired resistance makes it extremely challenging to identify antibiotics that are effective against Gram-negative bacteria. In this study, we have demonstrated the synergistic effect of outer membrane-permeable cationic polyurethanes with rifampicin, a polyketide that would otherwise be excluded by the OM, on different strains of E. coli, including a clinically isolated uropathogenic multidrug-resistant (MDR) E. coli. Rifampicin combined with a low-dose treatment of a cationic polyurethane reduced the MIC in E. coli of rifampicin by up to 64-fold. The compositions of cationic polyurethanes were designed to have low hemolysis and low cell cytotoxicity while maintaining high antibacterial activity. Our results demonstrate the potential to rescue the large number of available OM-excluded antibiotics to target normally resistant Gram-negative bacteria via synergistic action with these cationic polyurethanes, acting as a novel antibiotic adjuvant class.

Light-Activated Adhesion and Debonding of Underwater Pressure-Sensitive Adhesives.

Pressure-sensitive adhesives (PSAs) such as sticky notes and labels are a ubiquitous part of modern society. PSAs with a wide range of peel adhesion strength are designed by tailoring the bulk and surface properties of the adhesive. However, designing an adhesive with strong initial adhesion but showing an on-demand decrease in adhesion has been an enduring challenge in the design of PSAs. To address this challenge, we designed alkoxyphenacyl-based polyurethane (APPU) PSAs that show a photoactivated increase and decrease in peel strength. With increasing time of light exposure, the failure mode of our PSAs shifted from cohesive to adhesive failure, providing residue-free removal with up to 83% decrease in peel strength. The APPU-PSAs also adhere to substrates submerged underwater and show a similar photoinduced decrease in adhesion strength.

Peptidomimetic Polyurethanes Inhibit Bacterial Biofilm Formation and Disrupt Surface Established Biofilms.

Over 80% of all chronic bacterial infections in humans are associated with biofilms, which are surface-associated bacterial communities encased within a secreted exopolysaccharide matrix that can provide resistance to environmental and chemical insults. Biofilm formation triggers broad adaptive changes in the bacteria, allowing them to be almost 1000-fold more resistant to conventional antibiotic treatments and host immune responses. The failure of antibiotics to eliminate biofilms leads to persistent chronic infections and can promote the development of antibiotic-resistant strains. Therefore, there is an urgent need to develop agents that effectively prevent biofilm formation and eradicate established biofilms. Herein, we present water-soluble synthetic peptidomimetic polyurethanes that can disrupt surface established biofilms of Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli, all of which show tolerance to the conventional antibiotics polymyxin B and ciprofloxacin. Furthermore, while these polyurethanes show poor antimicrobial activity against planktonic bacteria, they prevent surface attachment and stimulate bacterial surface motility to inhibit biofilm formation of both Gram-positive and Gram-negative bacteria at subinhibitory concentrations, without being toxic to mammalian cells. Our results show that these polyurethanes show promise as a platform for the development of therapeutics that target biofilms and modulate surface interactions of bacteria for the treatment of chronic biofilm-associated infections and as antibiofilm agents.

Thread Size and Polymer Composition of 3D Printed and Electrospun Wound Dressings Affect Wound Healing Outcomes in an Excisional Wound Rat Model.

Thread size and polymer composition are critical properties to consider for achieving a positive healing outcome with a wound dressing. Three-dimensional (3D) printed scaffolds and electrospun mats both offer distinct advantages as replaceable wound dressings. This research aims to determine if the thread size and polymer compositions of the scaffolds affect skin wound healing outcomes, an aspect that has not been adequately explored. Using a modular polymer platform, four polyester direct-write 3D printed scaffolds and electrospun mats were fabricated into wound dressings. The dressings were applied to splinted, full thickness skin wounds in an excisional wound rat model and evaluated against control wounds to which no dressing was applied. Wound closure rates and reduction of the wound bed width were not affected by the thread size or polymer composition. However, epidermal thickness was larger in wounds treated with electrospun dressings and was slightly affected by the polymer composition. Two of the four tested polymer compositions lead to delayed reorganization of granulation tissues. Moreover, enhanced angiogenesis was seen in wounds treated with 3D printed dressings compared to those treated with electrospun dressings. The results from this study can be used to inform the choice of dressing architecture and polymer compositions to achieve positive wound healing outcomes.

Lower Critical Solution Temperature-Driven Self-Coacervation of Nonionic Polyester Underwater Adhesives.

To enable attachment to underwater surfaces, aquatic fauna such as mussels and sandcastle worms utilize the advantages of coacervation to deliver concentrated protein-rich adhesive cocktails in an aqueous environment onto underwater surfaces. Recently, a mussel adhesive protein Mfp-3s, was shown to exhibit a coacervation-based adhesion mechanism. Current synthetic strategies to mimic Mfp-3s often involve complexation of oppositely charged polymers. Such complex coacervates are more sensitive to changes in pH and salt, thereby limiting their utility to narrow ranges of pH and ionic strength. In this study, by taking advantage of the lower critical solution temperature-driven coacervation, we have created mussel foot protein-inspired, tropoelastin-like, bioabsorbable, nonionic, self-coacervating polyesters for the delivery of photo-cross-linkable adhesives underwater and to overcome the challenges of adhesion in wet or underwater environments. We describe the rationale for their design and the underwater adhesive properties of these nonionic adhesives. Compared to previously reported coacervate adhesives, these "charge-free" polyesters coacervate in wide ranges of pH (3-12) and ionic strength (0-1 M NaCl) and rapidly (<300 s) adhere to substrates submerged underwater. The study introduces smart materials that mimic the self-coacervation and environmental stability of Mfp-3s and demonstrate the potential for biological adhesive applications where high water content, salts, and pH changes can be expected.

Elucidating the Molecular Interactions of Encapsulated Doxorubicin within a Nonionic, Thermoresponsive Polyester Coacervate.

Thermoresponsive polymers that display a lower critical solution temperature (LCST) are attractive drug delivery systems (DDSs) due to their potential to encapsulate and release therapeutics in a sustained manner as a function of temperature input. To attain the full potential of such DDSs, methods that illustrate the details of drug-polymer interactions are necessary. Here, we synthesized a nonionic, coacervate-forming, thermoresponsive polyester to encapsulate doxorubicin (Dox) and used solution state NMR spectroscopy and fluorescence microscopy techniques to probe the interactions between the polymer and Dox at the molecular level. The incomplete dehydration provides a matrix for encapsulation of sensitive therapeutics and preserving their activity, while the low hysteresis property of the polyester provides rapid transition from soluble to coacervate phase. Saturation transfer difference (STD) NMR revealed the Dox-polymer interactions within the coacervates. 1H-1H nuclear Overhauser effect spectroscopy (NOESY) cross-peak differences of Dox confirmed the Dox-polymer interactions. Diffusion-ordered spectroscopy (DOSY) revealed the slower diffusion rate of Dox in the presence of polyester coacervates. These studies illustrate how the state of the polyester (below and above LCST) affects the polyester-Dox interactions and offers details of the specific functional groups involved in these interactions. Our results provide a framework for future investigations aimed at characterizing fundamental interactions in polymer-based DDSs.

Bacterial Membrane Selective Antimicrobial Peptide-Mimetic Polyurethanes: Structure-Property Correlations and Mechanisms of Action.

The rise in prevalence of antibiotic resistant strains of bacteria is a very significant challenge for treating life-threatening infections worldwide. A source of novel therapeutics that has shown great promise is a class of biomolecules known as antimicrobial peptides. Previously, within our laboratories, we developed a new family of water-soluble antimicrobial polyurethanes that mimic antimicrobial peptides. Within this current investigation, studies were carried out to gain a greater understanding of the structure/property relationships of the polyurethanes. This was achieved by synthesizing a variety of pendant group functionalized polyurethanes and testing their effectiveness as an antimicrobial by carrying out minimum inhibitory concentration testing and determining their compatibility with blood cells. Additionally, insight into the mode of action of the polyurethanes was obtained through experiments using dye encapsulated phospholipids and assays of bacterial cells that indicated the ability of the polyurethanes to penetrate and disrupt membranes. Collectively, the results indicate that the addition of hydrophobic, uncharged polar, and anionic moieties do not have a strong influence on the antimicrobial activity; yet, the addition of hydrophobic groups enhances cytoplasmic membrane disruption, a larger proportion of cationic pendant groups promotes greater outer membrane disruption of Gram negative bacteria, and uncharged polar groups and anionic groups improve compatibility of the polyurethanes with mammalian cells.

Viscosity Attunes the Adhesion of Bioinspired Low Modulus Polyester Adhesive Sealants to Wet Tissues.

Clinically used bio-based tissue sealants bring in the risk of animal-borne infections, non-degradability, allergic reactions, tissue compression, tissue necrosis, and poor wet adhesion. Motivated by these unsatisfactory properties of existing tissue sealants, herein, we designed a library of solvent- and initiator-free hydrophobic mussel-inspired degradable tissue adhesives that can stick and seal the epidermis, pericardium, and Glisson's capsule under physiologically relevant wet conditions. By varying the molar ratio of the functional groups, we obtained polyester adhesive sealants with similar surface energy and varying viscosity. The careful examination of the wetting behavior of these polyester adhesive sealants on tissue surfaces showed that the polyester adhesive sealant with lower viscosity has higher intrinsic work of adhesion, which allowed them to adhere to strongly hydrated surfaces such as pericardium and Glisson's capsule. Because of the lower intrinsic work of adhesion, the polyester adhesive sealant with higher viscosity only adhered to the relatively hydrophobic surface (epidermis). The strong wet adhesion to tissue surfaces, cell-compatibility, hydrolytic degradability, and radical scavenging nature of these polyester adhesive sealants make them potential candidates for wound closure procedures.

Structure-Activity Study of Antibacterial Poly(ester urethane)s with Uniform Distribution of Hydrophobic and Cationic Groups.

Infections associated with antibiotic-resistant bacteria have become a threat to the global public health. Antimicrobial polymers, which are synthetic mimics of antimicrobial peptides, have gained increasing attention, as they may have a lower chance of inducing resistance. The cationic-hydrophobic balance and distribution of cationic and hydrophobic moieties of these polymers is known to have a major effect on antimicrobial activity. We studied the properties of a series of facially amphiphilic antimicrobial surfactant-like poly(ester urethane)s with different hydrophobic pendant groups (P1, P2, and P3) and cationic groups distributed uniformly along the polymer chain. These polymers exhibited bactericidal activity against Gram-negative Escherichia coli and Pseudomonas aeruginosa, as well as Gram-positive Staphylococcus aureus and Staphylococcus epidermidis. Microscopy and dye release assays demonstrated that these polymers cause membrane disruption, which is dependent on the cationic-hydrophobic ratio in the polymer. Membrane permeability assays revealed that these polymers can permeabilize the outer membrane of E. coli and damage the cytoplasmic membrane of both E. coli and S. aureus. In addition, our results indicate that the three polymers exhibit a different extent of membrane disruption against E. coli. P1 caused minor damage to the cytoplasmic membrane integrity, but it was able to dissipate the cytoplasmic membrane potential, leading to cell death. P2 and P3 depolarized the cytoplasmic membrane and also caused significant damage to the cytoplasmic membrane. Overall, we showed a new class of broad-spectrum bactericidal polymers whose membrane disrupting ability against E. coli correlates with the structural differences of the hydrophobic pendant groups.

Pendant Functionalized Polyester Nanofibers with Dual Cargo Release.

Common polymeric biomaterials lack the ability to control the release of multiple bioactive compounds due to their inherent lack of functionality. These materials often require additional components or complicated fabrication techniques to achieve the separate release profiles desired for wound healing and tissue engineering applications. This prevents many biomaterials from being translated to the clinic, because the complexity of the wound environment necessitates temporal control of multiple additives for effective healing. Electrospun nanofibers comprised of a functional polymer would allow for separate release profiles of multiple bioactive compounds through covalent conjugation or tuning noncovalent interactions. In this work, two fluorescent dyes as model drugs were released from functional polyester electrospun mats. Two mats were fabricated: one in which both dyes were blended into the electrospinning solution and one in which one dye was blended and the other was covalently conjugated to the polymer. Average fiber diameters were determined using scanning electron microscopy, while fluorescence microscopy showed the presence of both dyes in the fibers. Dye release was tracked using UV-vis spectroscopy by comparing measured values to standard curves. Finally, degradation of the mats was tracked using gel permeation chromatography. With this functional polyester platform, distinct release profiles were achieved for two model drugs. Not only does the release of two model drugs show potential for the future use of this polymer platform in the applications of wound healing and tissue engineering but also the ability to incorporate several distinct conjugation chemistries is of great benefit.

Effect of Dexamethasone on Room Temperature Three-Dimensional Printing, Rheology, and Degradation of a Low Modulus Polyester for Soft Tissue Engineering.

Three-dimensional (3D) printing has enabled benchtop fabrication of customized bioengineered constructs with intricate architectures. Various approaches are being explored to enable optimum integration of such constructs into the physiological environment including addition of bioactive fillers. In this work, we incorporated a corticosteroid drug, dexamethasone (Dex), in a low modulus polyester (SC5050) and examined the effect of Dex incorporation on solvent-, initiator-, and monomer-free pneumatic extrusion-based 3D printing of the polymer. Dex-SC5050 interactions were characterized by plotting thermodynamic binary phase diagrams based on the Flory-Huggins theory. The effect of Dex composition on the 3D printability of the SC5050 polyester was examined by rheological characterization and by image analysis of each layer of the 3D printed scaffolds. The drug release and the degradation of the polymer from the 3D printed scaffolds was used to analyze the effect of Dex composition on the performance of the 3D printed scaffolds. We found that Dex was insoluble in SC5050 polyester at relevant 3D printing temperatures and the insoluble drug particles physically reinforced the polymer, increasing the viscosity and the shear modulus of the base polymer. In addition, the reinforcing effect improved the shape fidelity of the printed filaments and the overall quality of the scaffolds. The Dex particles demonstrated a two-phase release, with an initial burst release and a slower sustained release of drug under in vitro conditions. To investigate preliminary host response of the 3D printed SC5050 scaffolds for tissue engineering applications, the printed scaffolds were implanted subcutaneously in Sprague-Dawley rats for 6 weeks and examined for fibrous tissue formation, infiltration of cells, and vascularization into the pores of the scaffolds.

Direct Observation of the Interplay of Catechol Binding and Polymer Hydrophobicity in a Mussel-Inspired Elastomeric Adhesive.

Marine organisms such as mussels have mastered the challenges in underwater adhesion by incorporating post-translationally modified amino acids like l-3,4-dihydroxyphenylalanine (DOPA) in adhesive proteins. Here we designed a catechol containing elastomer adhesive to identify the role of catechol in interfacial adhesion in both dry and wet conditions. To decouple the adhesive contribution of catechol to the overall adhesion, the elastomer was designed to be cross-linked through [2 + 2] photo-cycloaddition of coumarin. The elastomer with catechol moieties displayed a higher adhesion strength than the catechol-protected elastomer. The contact interface was probed using interface-sensitive sum frequency generation spectroscopy to explore the question of whether catechol can displace water and bond with hydrophilic surfaces. The spectroscopy measurements reveal that the maximum binding energy of the catechol and protected-catechol elastomers to sapphire substrate is 7.0 ± 0.1 kJ/(mole of surface O-H), which is equivalent to 0.10 J/m2. The higher dry and wet adhesion observed in the macroscopic adhesion measurements for the catechol containing elastomer originates from multiple hydrogen bonds of the catechol dihydroxy groups to the surface. In addition, our results show that catechol by itself does not remove the confined interstitial water. In these elastomers, it is the hydrophobic groups that help in partially removing interstitial water. The observation of the synergy between catechol binding and hydrophobicity in enabling the mussel-inspired soft adhesive elastomer to stick underwater provides a framework for designing materials for applications in tissue adhesion and moist-skin wearable electronics.

Multi-purposable filaments of HPMC for 3D printing of medications with tailored drug release and timed-absorption.

Three-dimensional printing (3DP), though developed for nonmedical applications and once regarded as futuristic only, has recently been deployed for the fabrication of pharmaceutical products. However, the existing feeding materials (inks and filaments) that are used for printing drug products have various shortcomings, including the lack of biocompatibility, inadequate extrudability and printability, poor drug loading, and instability. Here, we have sought to develop a filament using a single pharmaceutical polymer, with no additives, which can be multi-purposed and manipulated by computational design for the preparation of tablets with desired release and absorption patterns. As such, we have used hydroxypropyl-methylcellulose (HPMC) and diltiazem, a model drug, to prepare both drug-free and drug-impregnated filaments, and investigated their thermal and crystalline properties, studied the cytotoxicity of the filaments, designed and printed tablets with various infill densities and patterns. By alternating the drug-free and drug-impregnated filaments, we fabricated various types of tablets, studied the drug release profiles, and assessed oral absorption in rats. Both diltiazem and HPMC were stable at extrusion and printing temperatures, and the drug loading was 10% (w/w). The infill density, as well as infill patterns, influenced the drug release profile, and thus, when the infill density was increased to 100%, the percentage of drug released dramatically declined. Tablets with alternating drug-free and drug-loaded layers showed delayed and intermittent drug release, depending on when the drug-loaded layers encountered the dissolution media. Importantly, the oral absorption patterns accurately reproduced the drug release profiles and showed immediate, extended, delayed and episodic absorption of the drug from the rat gastrointestinal tract (GIT). Overall, we have demonstrated here that filaments for 3D printers can be prepared from a pharmaceutical polymer with no additives, and the novel computational design allows for fabricating tablets with the capability of producing distinct absorption patterns after oral administration.

Efficient Protein Encapsulation within Thermoresponsive Coacervate-Forming Biodegradable Polyesters.

Presented here is a novel method for encapsulating proteins into biodegradable, thermoresponsive coacervate-type polyesters. Bovine serum albumin (BSA) was efficiently incorporated into coacervate droplets via a simple thermoresponsive encapsulation mechanism. Tunable modular systems for encapsulation such as the one presented here may be useful in a range of protein delivery applications.

Nontoxic Cationic Coumarin Polyester Coatings Prevent Pseudomonas aeruginosa Biofilm Formation.

The rapid increase in bacterial infections and antimicrobial resistance is a growing public health concern. Infections arising from bacterial contamination of surgical tools, medical implants, catheters, and hospital surfaces can potentially be addressed by antimicrobial polymeric coatings. The challenge in developing such polymers for in vivo use is the ability to achieve high antimicrobial efficacy while at the same time being nontoxic to human cells. Although several classes of antimicrobial polymers have been developed, many of them cannot be used in the clinical setting due to their nonselective toxicity toward bacteria and mammalian cells. Here, we demonstrate that coumarin polyesters with cationic pendant groups are very effective against Gram negative Pseudomonas aeruginosa. Coumarin polyesters with pendant cationic amine groups were coated onto glass coverslips and tested for their antimicrobial activity against P. aeruginosa colonization of the surface. The results demonstrate that the cationic coumarin polyester kills the surface attached bacterial cells preventing biofilm formation but does not show any hemolytic activity or discernible toxicity toward mammalian cells. The antimicrobial polyesters described in this work have several advantages desired in antimicrobial coatings such as high antimicrobial activity, low toxicity toward mammalian cells, visualization and ease of synthesis and fabrication, all of which are necessary for translation to the clinic.