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.Keywords: antimicrobial coating; antimicrobial polyester; cationic polymer coating; functionalized polyester; nontoxic antimicrobial polymer; Pseudomonas aeruginosa biofilm;

Synthetic polymers exhibiting reversible lower critical solution temperature (LCST), such as poly(N-isopropylacrylamide) (PNIPAM), are intriguing materials with various potential applications. We recently developed a new class of biodegradable thermoresponsive polyesters (TR-PEs) based on N-substituted diol monomers. TR-PEs exhibited reversible cloud point temperatures (Tcp) between 0–50 °C and were shown to be non-cytotoxic. The synthesis of N-substituted diols and TR-PEs is highly modular, allowing for a wide variety of possible homo- and copolyesters. In this work, we report the synthesis and characterization of 20 homopolyesters in order to better understand the structure–property relationship of TR-PEs. UV-vis spectroscopy showed that the Tcp of TR-PEs was highly dependent on pendant group structure, such as secondary or tertiary amides, cyclic and linear groups, and substitution of oxygen atoms. Structure-Tcp analysis provides a correlation between Tcp and the number of heteroatoms relative to the number of carbon atoms in the pendant group thereby providing a rationale for the design of thermoresponsive polyesters with desired Tcp values. To demonstrate the expanded tunability of the TR-PE system, copolyesters bearing covalently attached ibuprofen were synthesized and shown to exhibit LCST behavior dependent on comonomer hydrophilicity.

Polymers with controlled sequence can exhibit unique properties and functions compared to their random counterparts. While many methodologies have been utilized to synthesize sequence-controlled polymers, there is still a strong need to build a fundamental understanding of sequence–property correlations. Here we report the design and development of an alternating pendant-functionalized polyester and compare it to a random polyester of the same composition. Our results showed that such polyesters exhibit distinct physical properties compared to their random counterparts. It was found that polyesters with controlled alternating sequences are less ductile and exhibit higher Young's modulus compared to random polyesters. The alternating and random polyesters showed distinctly different hydrolytic degradation profiles. Fluorescence quenching studies showed that the sequence of the polyesters influences their ability to interact with fluoride ions. These interesting results suggest that polyesters with alternating pendant groups exhibit unique properties and would allow access to different applications.

AbstractRecognizing the potential for synthetic adhesives that can function in wet environments, elements of mussel foot proteins such as L-3,4-dihydroxyphenylalanine (DOPA) and phosphoserine have been incorporated into synthetic adhesives. Such adhesives have corroborated the advantage of surface active groups like DOPA, but have not yet demonstrated superior performance in wet or underwater environments, without using organic solvents. What has been conspicuously absent from such designs is the effect of hydrophobic components in the performance of underwater adhesives. Herein it is shown that incorporation of hydrophobic groups in low modulus polyester adhesives provides very high lap-shear strength and resistance to water penetration. In addition to the excellent performance in wet conditions, the designed adhesive can be applied underwater without any solvent, is biodegradable, and is designed from soybean oil, which is a readily available and renewable resource.

Recently, we reported a new class of biodegradable, thermoresponsive polyesters (TR-PEs) inspired by polyacrylamides and elastin-like peptides (ELPs). The polyesters exhibit tunable cloud point temperatures (Tcp) and thermoresponsive coacervation in aqueous solution as shown via UV-vis spectroscopy, 1H NMR, and DLS. However, the Tcp of all TR-PEs remained low (<15 °C), and higher thermoresponsivity would be beneficial for many applications. This study examines the synthesis, polymerization, and analysis of a new monomer bearing a more hydrophilic pendant group, bis-2-methoxyethylamine (bMoEtA). The resulting TR-PE, TR-bMoEtAPE, displays a threefold increase in Tcp (ca. 50 °C) that is affected by solution (DI water vs. phosphate buffered saline), concentration (1–40 mg mL−1) molecular weight (20–130 kDa), and cosolutes (Hofmeister salts and urea). The Tcp and Tg of random TR-bMoEtAPE copolymers can be tuned via comonomer feed. Variable temperature 1H NMR indicated a cooperative coacervation mechanism above Tcp, further reinforced by DLS measurements. As evidenced by UV-vis and SEC analysis, TR-bMoEtAPE underwent rapid degradation over a period of 7 days in DI water and PBS. Finally, cytotoxicity studies suggested that TR-bMoEtAPE is non-cytotoxic even at high concentrations (ca. 1000 μg mL−1). The increased Tcp and tunability suggests TR-bMoEtAPE as a potential candidate for future functionalized TR-PE therapeutic-delivery systems.

3D printing has enabled the design of biomaterials into intricate and customized scaffolds. However, current 3D printed biomaterial scaffolds have potential drawbacks due to residual monomers, free-radical initiators, solvents, or printing at elevated temperatures. This work describes a solvent, initiator, and monomer-free degradable polyester platform for room temperature 3D printing. Linoleic acid side chains derived from soybean oil lowers the Tg and prevents packing and entanglement, ensuring that G″ > G′ during room temperature printing. Upon printing, cross-linking of pendant functionalized coumarin moieties fixes the viscous filaments to elastomeric solids. Furthermore, the modular design of the polyester platform enables conjugation of ligands, as demonstrated by the conjugation of FITC to surface amines on the 3D printed scaffolds. This low modulus, printable polyester platform addresses several design challenges in 3D printing of functional biomaterials and could potentially be useful in many tissue engineering applications.

We report on a new class of thermoresponsive biodegradable polyesters (TR-PE) inspired by polyacrylamides and elastin-like proteins (ELPs). The polyesters display reversible phase transition with tunable cloud point temperatures (Tcp) in aqueous solution as evidenced by UV–vis spectroscopy, 1H NMR, and DLS measurements. These polyesters form coacervate droplets above their lower critical solution temperature (LCST). The Tcp of the polyesters is influenced by the solutes such as urea, SDS, and NaCl. The Tcp of the copolymers shows a linear correlation with the composition of the polyesters indicating the ability to tune the phase change temperature. We also show that such thermoresponsive coacervates are capable of encapsulating small molecules such as Nile Red. Furthermore, the polyesters are hydrolytically degradable.

•Reproducible block sizes with microwave assisted RAFT polymerization.•Dual end functionalization of polyacrylate diblock copolymers.•Control of micelle size by tuning size of hydrophobic block.•Characterization of α- and ω-chain end functionalizations.This work demonstrates the preparation of amphiphilic block copolymers with remarkable reproducibility of each block and the dual functionalization of the chain ends with a targeting unit and a fluorescent moiety. The size of the resulting micelles can be controlled between 17 and 55 nm by tuning the size of the hydrophobic block. The polymerization of the diblock was carried out by microwave assisted reversible addition fragmentation chain transfer (RAFT) polymerization and results in a very high degree of reproducibility of the number of repeat units of each block. The hydrophilic block of the polymer comprised of poly(2-hydroxyethyl acrylate) (pHEA) while the hydrophobic block was made of poly(2-ethylhexyl acrylate) (pEHA). Folic acid, a folate receptor targeting moiety, was tethered to the α end of the polymer while anthracene was covalently linked to the ω end. The ω end covalent attachment is via a redox cleavable disulfide bond, which is optimal for controlled drug delivery systems. High efficiencies of α- and ω-conjugations were obtained as determined by UV and NMR measurements.

Guidance and migration of cells in the nervous system is imperative for proper development, maturation, and regeneration. In the peripheral nervous system (PNS), it is challenging for axons to bridge critical-sized injury defects to achieve repair and the central nervous system (CNS) has a very limited ability to regenerate after injury because of its innate injury response. The photoreactivity of the coumarin polyester used in this study enables efficient micropatterning using a custom digital micromirror device (DMD) and has been previously shown to be biodegradable, making these thin films ideal for cell guidance substrates with potential for future in vivo applications. With DMD, we fabricated coumarin polyester thin films into 10 × 20 μm and 15 × 50 μm micropatterns with depths ranging from 15 to 20 nm to enhance nervous system cell alignment. Adult primary neurons, oligodendrocytes, and astrocytes were isolated from rat brain tissue and seeded onto the polymer surfaces. After 24 h, cell type and neurite alignment were analyzed using phase contrast and fluorescence imaging. There was a significant difference (p < 0.0001) in cell process distribution for both emergence angle (from the body of the cell) and orientation angle (at the tip of the growth cone) confirming alignment on patterned surfaces compared to control substrates (unpatterned polymer and glass surfaces). The expected frequency distribution for parallel alignment (≤15°) is 14% and the two micropatterned groups ranged from 42 to 49% alignment for emergence and orientation angle measurements, where the control groups range from 12 to 22% for parallel alignment. Despite depths being 15 to 20 nm, cell processes could sense these topographical changes and preferred to align to certain features of the micropatterns like the plateau/channel interface. As a result this initial study in utilizing these new DMD micropatterned coumarin polyester thin films has proven beneficial as an axon guidance platform for future nervous system regenerative strategies.Keywords: Axon guidance; cortical neurons; glial cells; micropatterned polymers; nanotopography; nervous system regeneration; photoreactive polymers

The synthesis and photochemical characterization of two classes of photoresponsive polyesters are described. These polyesters contain either alkoxyphenacyl or coumarin chromophores embedded along the polymer chain. The alkoxyphenacyl polyesters undergo efficient photoinduced chain scission upon irradiation at 300 nm in solution or as a nanoparticle suspension. At 254 nm the coumarin polyesters undergo polymer chain scission. Irradiation of the coumarin polyesters in solution at 350 nm results in both chain crosslinking and chain scission behavior, while irradiation of the coumarin polyesters as nanoparticles results in chain crosslinking. The properties of the alkoxyphenacyl and coumarin polyesters are influenced by the choice of diacid as seen from their thermal behavior. The use of glutamic acid enabled surface or bulk functionalization of the photoresponsive polymers. In addition, controlled release of Nile Red from coumarin polyester nanoparticles is demonstrated by modulation of the wavelength and intensity of irradiation.

Photoresponsive thin films are commonly encountered as high performance coatings as well as critical component, photoresists, for microelectronics manufacture. Despite intensive investigations into the dynamics of thin glassy polymer films, studies involving reactions of thin films have typically been limited by difficulties in decoupling segregation of reacting components or catalysts due to the interfaces. Here, thin films of coumarin polyesters overcome this limitation where the polyester undergoes predominately cross-linking upon irradiation at 350 nm, while chain scission occurs with exposure to 254 nm light. Spectroscopic ellipsometry is utilized to track these reactions as a function of exposure time to elucidate the associated reaction kinetics for films as thin as 15 nm. The cross-linking appears to follow a second order kinetic rate law, while oxidation of the coumarin that accompanies the chain scission and enables this reaction to be tracked spectroscopically appears to be a first order reaction in coumarin concentration. Because of the asymmetry in the coumarin diol monomer and the associated differences in local structure that result during formation of the polyester, two populations of coumarin are required to fit the reaction kinetics; 10–20% of the coumarin is significantly more reactive, but these groups appear to undergo chain scission/oxidation at both wavelengths. These reaction rate constants are nearly independent (within 1 order of magnitude) of film thickness down to 15 nm. There is maximum rate at a finite thickness for the 254 nm exposure, which we attribute to constructive interference of the UV radiation within the polymer film, rather than typical confinement effects; no thickness dependence in reaction rates is observed for the 350 nm exposure. The utilization of a single polymer with two distinct reactions enables unambiguous investigation of thickness effects on reactions.

The Baylis–Hillman reaction, which is a carbon–carbon bond forming reaction between an aldehyde and an activated alkene, was utilized to prepare densely functionalized monomers suitable for chain and step polymerization. By reacting formaldehyde with various alkyl acrylates, a series of alkyl α-hydroxymethyl acrylate monomers were synthesized. These monomers efficiently underwent RAFT polymerization to provide α-hydroxymethyl-substituted polyacrylates with well controlled molecular weight and low polydispersity. The resulting homopolymers were also efficient macro-chain transfer agents for further RAFT polymerization. The Baylis–Hillman reaction was also utilized to synthesize alkene functionalized diols which underwent step-growth polymerization to provide polyesters and poly(ester urethane)s. Furthermore, it was demonstrated that the alkene group can be quantitatively functionalized by thiol–ene click chemistry to provide a series of polymers with diverse physical properties.

The synthesis and properties of a new class of photoresponsive coumarin polyesters are described. Incorporation of the coumarin chromophore in the polymer chain provides interesting properties such as polymer chain cross-linking upon irradiation at 350 nm and chain un-cross-linking when irradiated at 254 nm. In addition, irradiation at 254 nm also results in polymer chain scission. The cross-linking, un-cross-linking, and chain scission properties were studied by ssNMR, ATR-IR, and GPC measurements. These properties enable the fabrication of 2D surfaces having complementary micropatterned features. Also, initial biocompatibility profiles of the polymers and their irradiation products were demonstrated using MTT assays.

The synthesis and characterization of a library of modular multifunctional polyesters with pendant functional groups are described. The polyesters were synthesized at room temperature by carbodiimide-mediated polymerization of pendant functionalized diols and succinic acid. The pendant groups are designed to mimic the side chains of peptides, and it is shown that the physical properties of the polyesters can be modulated over a wide range by the choice of pendant groups. We also show that the pendant groups can be orthogonally functionalized with ligands such as fluorophores, poly(ethylene glycol) (PEG) or Arg-Gly-Asp (RGD).

We report the design and development of a new class of alkoxyphenacyl based photodegradable polycarbonates. These polymers incorporate the photoactive moiety in the backbone and, when irradiated at 300 nm, undergo controlled chain scission. Micropatterned thin films of these polymers were fabricated by photolithographic techniques. The use of these photodegradable polymers for controlled release applications was demonstrated by the release of Nile Red from polymeric nanoparticles. In addition, these polymers are mechanically robust, thermally stable, and hydrolytically degradable.