Hydrogel dressings with intrinsic antibiofilm and antioxidative dual functionalities accelerate infected diabetic wound healing.

Chronic wounds are often infected with biofilm bacteria and characterized by high oxidative stress. Current dressings that promote chronic wound healing either require additional processes such as photothermal irradiation or leave behind gross amounts of undesirable residues. We report a dual-functionality hydrogel dressing with intrinsic antibiofilm and antioxidative properties that are synergistic and low-leaching. The hydrogel is a crosslinked network with tethered antibacterial cationic polyimidazolium and antioxidative N-acetylcysteine. In a murine diabetic wound model, the hydrogel accelerates the closure of wounds infected with methicillin-resistant Staphylococcus aureus or carbapenem-resistant Pseudomonas aeruginosa biofilm. Furthermore, a three-dimensional ex vivo human skin equivalent model shows that N-acetylcysteine promotes the keratinocyte differentiation and accelerates the re-epithelialization process. Our hydrogel dressing can be made into different formats for the healing of both flat and deep infected chronic wounds without contamination of the wound or needing other modalities such as photothermal irradiation.

Cationic Carbon Monoxide-Releasing Polymers as Antimicrobial and Antibiofilm Agents by the Synergetic Activity.

Recent studies indicate that carbon monoxide-releasing molecules (CORMs), a class of organometallic compounds, exert antibacterial activities through the delivery of carbon monoxide (CO) molecules. We developed a new-class CO-delivery system by conjugating classical low-molecular-weight CORMs (i.e., [Ru(CO)3Cl2]2 and Mn(CO)5Br) onto a positively charged carrier, polyimidazolium (PIM), giving cationic CO-releasing polymers Ru@PIM and Mn@PIM, respectively. Compared with low-molecular-weight CORMs, our polymeric CO vehicles showed improved water solubility, reduced cytotoxicity, significantly extended CO-releasing duration, and enhanced antimicrobial ability against both planktonic and biofilm microorganisms. Ru@PIM and Mn@PIM inhibited the growth of a broad spectrum of free Gram-positive and Gram-negative bacteria as well as fungus with the lowest minimum inhibitory concentration (MIC) at 8 µg/mL. They were effective in preventing pathogenic Pseudomonas aeruginosa biofilm formation with biofilm reduction by more than 92% at 16 µg/mL and 99% at 32 µg/mL. They also demonstrated potent dispersal efficacy on recalcitrant well-established biofilms through a synergetic activity with a biofilm log10 reduction of 2.5-3.2 ≥ 64 µg/mL and nearly 2.0 at the concentration of as low as 16 µg/mL. This CO-releasing system may retain long-time antimicrobial ability after the complete release of CO molecules owing to the cationic structure. The novel CO-releasing polymers have great potential as antimicrobial and antibiofilm agents in biomedical applications.

Smart Multifunctional Polymer Systems as Alternatives or Supplements of Antibiotics To Overcome Bacterial Resistance.

In recent years, infectious diseases have again become a critical threat to global public health largely due to the challenges posed by antimicrobial resistance. Conventional antibiotics have played a crucial role in combating bacterial infections; however, their efficacy is significantly impaired by widespread drug resistance. Natural antimicrobial peptides (AMPs) and their polymeric mimics demonstrate great potential for killing bacteria with low propensity of resistance as they target the microbial membrane rather than a specific molecular target, but they are also toxic to the host eukaryotic cells. To minimize antibiotics systemic spread and the required dose that promote resistance and to advocate practical realization of the promising activity of AMPs and polymers, smart systems to target bacteria are highly sought after. This review presents bacterial recognition by various specific targeting molecules and the delivery systems of active components in supramolecules. Bacteria-induced activations of antimicrobial-based nanoformulations are also included. Recent advances in the bacteria targeting and delivery of synthetic antimicrobial agents may assist in developing new classes of highly selective antimicrobial systems which can improve bactericidal efficacy and greatly minimize the spread of bacterial resistance.

High-Density Three-Dimensional Network of Covalently Linked Nitric Oxide Donors to Achieve Antibacterial and Antibiofilm Surfaces.

Bacterial colonization on biomedical devices often leads to biofilms that are recalcitrant to antibiotic treatment and the leading cause of hospital-acquired infections. We have invented a novel pretreatment chemistry for device surfaces to produce a high-density three-dimensional (3-D) network of covalently linked S-nitrosothiol (RSNO), which is a nitric oxide (NO) donor. Poly(polyethylene glycol-hydroxyl-terminated) (i.e., PPEG-OH) brushes were grafted from an ozone-pretreated polyurethane (PU) surface. The high-density hydroxyl groups on the dangling PPEG-OH brushes then underwent condensation with a mercapto-silane (i.e., MPS, mercaptopropyl trimethoxysilane) followed by S-nitrosylation to produce a 3-D network of NO-releasing RSNO to form the PU/PPEG-OH-MPS-NO coating. This 3-D coating produces NO flux of up to 7 nmol/(cm2 min), which is nearly 3 orders of magnitude higher than the picomole/(cm2 min) levels of other NO-releasing biomedical implants previously reported. The covalent immobilization of RSNO avoids donor leaching and reduces the risks of cytotoxicity arising from leachable RSNO. Our coated PU surfaces display good biocompatibility and exhibit excellent antibiofilm formation activity in vitro (up to 99.99%) against a broad spectrum of Gram-positive and Gram-negative bacteria. Further, the high-density RSNO achieves nearly 99% and 99.9% in vivo reduction of Pseudomonas aeruginosa (P. aeruginosa) and methicillin-resistant Staphylococcus aureus (MRSA) in a murine subcutaneous implantation infection model. Our surface chemistry to create high NO payload without NO-donor leaching can be applied to many biomedical devices.

Mixed-charge pseudo-zwitterionic copolymer brush as broad spectrum antibiofilm coating.

Zwitterionic polymers are classical antifouling polymers but they require specialized monomers that have cationic and anionic charges integrated into a single monomer. Herein, we show that pseudo-zwitterionic copolymers synthesized from a mixture of 2 monomers each having a single opposite polarity has excellent antibiofilm efficacy. We have discovered a new mixed-charge copolymer brush (#1-A) synthesized from 2 oppositely charged monomers, the anionic SPM (3-Sulfopropyl methacrylate) and the cationic AMPTMA ((3-Acrylamidopropyl) trimethylammonium chloride), that achieves broad spectrum in vitro antibiofilm effect of greater than 99% reductions against all six Gram-positive and Gram-negative bacteria tested. In the murine subcutaneous wound catheter infection models, the #1-A has good long-term anti-biofilm efficacy against MRSA and Pseudomonas aeruginosa of 3.41 and 3.19 orders respectively, outperforming previous mixed-charge copolymer coatings. We discovered a new method to choose the cationic/anionic pair combination to form the best antibiofilm copolymer brush coating by exploiting the solution polymerization kinetics disparity between the cationic and anionic monomers. We also showed that #1-A is softer and has higher hydration than the classical zwitterionic polymer. This study shows the possibility of achieving potent antibiofilm efficacy by combining readily available opposite singly charged monomers.

Robust anti-infective multilayer coatings with rapid self-healing property.

Surface coatings are extensively applied on biomedical devices to provide protection against biofouling and infections. However, most surface coatings prevent both bacteria and cells interactions with the biomaterials, limiting their uses as implants. Furthermore, damage to the surface such as scratches and abrasions can happen during transport and clinical usage, resulting in the loss of antibacterial property. In this work, we introduce an efficient method to fabricate stable anti-infective and self-healable multilayer coatings on stainless steel surface via a three-step procedue. Firstly, modified polyethyleneimine (PEI) and poly(acrylic acid) (PAA), both contain pendant furan groups, were deposited on the surface using Layer-by-Layer (LbL) self-assembly technique. Secondly, the polymer layers were cross-linked, via Diels-Alder cycloaddition, using a bismaleimide poly(ethylene glycol) linker, to enhance the stability of the coatings. Thirdly, the Diels-Alder adduct was utilised in the thiol-ene click reaction for post-modification of the coatings, which allowed for the grafting of antimicrobial poly(hexamethylene biguanide) (PHMB) and ε-poly(lysine) (EPL). The resultant multilayer coatings not only exhibited rapid self-healing property, with complete scratch closure within 30 min, but also demonstrated effective antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In addition, biofouling of bovine serum albumin was found to be inhibited on the coated surfaces. Furthermore, these coatings showed no toxicity effect towards seeded osteoblastic cells (MC3T3-E1) and evidence of anti-inflamatory activity when tested against macrophage cell line U-937. Our coating method thus represents an effective strategy for the anti-infective protection of biomedical-devices having direct contact with tissues.

Nontoxic Antimicrobial Cationic Peptide Nanoconstructs with Bacteria-Displaceable Polymeric Counteranions.

Antimicrobial peptides that target the integrity of bacterial envelopes can eradicate pathogens with little development of resistance, but they often inflict nonselective toxicity toward mammalian cells. The prevailing approach to optimize the selectivity of cationic peptides has been to modify their composition. Instead, we invent a new generation of broad-spectrum antibacterial nanoconstructs with negligible mammalian cell toxicity through a competitive displacement of counter polyanions from the complementary polycations. The nanoconstruct, which has a highly cationic Au nanoparticles (NPs) core shielded by polymeric counterions, is inert in nonbacterial environments. When exposed to negatively charged bacterial envelopes, this construct sheds its polyanions, triggering a cationic Au NP/bacterial membrane interaction that rapidly kills Gram-positive and Gram-negative bacteria. The anionic charge and hydrophilicity of the polyanion provides charge neutralization for the peptide-decorated Au NP core, but it is also bacteria-displaceable. These results provide a foundation for the development of other cationic particles and polymeric counterion combinations with potent antimicrobial activity without toxicity.

Smart nanomicelles with bacterial infection-responsive disassembly for selective antimicrobial applications.

New generation antimicrobial agents are expected to exhibit non-metabolic killing mechanisms, high killing potency and biocompatibility. We synthesized a cationic chitosan derivative and an anionic chitosan derivative - specifically an α-poly(l)lysine side-grafted chitosan (CS-PLL) and an anionic citraconyl anhydride (CA) modified polylysine side graft for chitosan (CS-PLL-CA). The ß-carboxylic amide of CS-PLL-CA is pH-labile and self-cleavable under pH 6 or below. When we mixed the cationic (CS-PLL) and anionic (CS-PLL-CA) peptidosaccharide copolymers, they self-assembled, due to electrostatic charge interactions, into nanomicelles (NMs) with the oppositely charged peptides in the core and the chitosan polysaccharide arms on the shell. The NMs exhibited high hemo- and cytocompatibility (nontoxic) at physiological pH of 7.4, due to the chitosan protection on the shell and charge neutralization on the core. Upon reaching the bacterial infection site, the chitosan shell interacted and accumulated around the bacteria. The bacterial infection sites in the body usually show localized acidity as a result of the combined actions of bacterial metabolism and host immune response, and the pH can decrease to as low as 5.5. At this low pH, the ß-carboxylic amide bond of the anionic polypeptide gradually hydrolyzed to expose the initial cationic amine moieties, causing the NMs to 'decompose' into individual CS-PLL and 'spill' the cationic molecules which then disrupted and killed the bacteria. This 'smart' bacteria-recognizing chitosan-decorated nanosystem opens the pathway to explore other anionic and cationic and biocompatible polymers for 'stealth' delivery of antimicrobial polypeptide, and 'on-demand' recovery of the cationic parts to kill bacteria at infection sites.

Precisely Structured Nitric-Oxide-Releasing Copolymer Brush Defeats Broad-Spectrum Catheter-Associated Biofilm Infections In Vivo.

Gram-negative bacteria cannot be easily eradicated by antibiotics and are a major source of recalcitrant infections of indwelling medical devices. Among various device-associated infections, intravascular catheter infection is a leading cause of mortality. Prior approaches to surface modification, such as antibiotics impregnation, hydrophilization, unstructured NO-releasing, etc., have failed to achieve adequate infection-resistant coatings. We report a precision-structured diblock copolymer brush (H(N)-b-S) composed of a surface antifouling block of poly(sulfobetaine methacrylate) (S) and a subsurface bactericidal block (H(N)) of nitric-oxide-emitting functionalized poly(hydroxyethyl methacrylate) (H) covalently grafted from the inner and outer surfaces of a polyurethane catheter. The block copolymer architecture of the coating is important for achieving good broad-spectrum anti-biofilm activity with good biocompatibility and low fouling. The coating procedure is scalable to clinically useful catheter lengths. Only the block copolymer brush coating ((H(N)-b-S)) shows unprecedented, above 99.99%, in vitro biofilm inhibition of Gram-positive and Gram-negative bacteria, 100-fold better than previous coatings. It has negligible toxicity toward mammalian cells and excellent blood compatibility. In a murine subcutaneous infection model, it achieves >99.99% biofilm reduction of Gram-positive and Gram-negative bacteria compared with <90% for silver catheter, while in a porcine central venous catheter infection model, it achieves >99.99% reduction of MRSA with 5-day implantation. This precision coating is readily applicable for long-term biofilm-resistant and blood-compatible copolymer coatings covalently grafted from a wide range of medical devices.

Understanding the Roughness-Fouling Relationship in Reverse Osmosis: Mechanism and Implications.

This paper investigates the relationship between roughness and fouling in reverse osmosis (RO) through specially designed experimental protocols and computational fluid dynamics (CFD) studies. Conventional polyamide thin-film composite membranes with a ridge-and-valley structure and an emerging type of smooth membranes are prepared. A wide range of foulants are used, and fouling under static, crossflow, and RO conditions are tested. Feature size on the membrane surface is important when foulants and the microscale structure show a similar size, and otherwise membrane-foulant interactions govern the static attachment. Under crossflow mode, fouling on the ridge-and-valley surface is not reduced to the same extent as that on smooth membranes, with the insufficient vortices in the valley region being identified as the key factor by CFD studies. In RO, uneven flux distribution as confirmed by gold nanoparticle filtration is also found to account for the much higher fouling rate of conventional membranes. Our study then suggests two strategies to design next-generation fouling-resistant RO membranes via structural optimization: first, a smooth selective layer should be maintained to ensure uniform flux distribution; second, one may mimic nature to fabricate patterned porous membranes as the support, so that it optimizes hydrodynamics while maintaining even fluxes.

Amino-containing tannic acid derivative-mediated universal coatings for multifunctional surface modification.

The development of a universal coating strategy for the construction of functional surfaces and modulation of surface properties is of great research interest. Tannic acid (TA) could serve as a sole precursor for the deposition of colorless coatings on substrate surfaces. However, the deposition of TA requires a high salt concentration (0.6 M), which may limit its practical application. Herein, primary amine moieties were introduced on the gallic acid groups in TA. The resultant amine-containing TA derivative (TAA) can self-polymerize under mild conditions (10 mM, Tris buffer), and form uniform and colorless coatings in a material-independent manner. In comparison with the TA coating under the same preparation conditions, the TAA coating exhibits an increased thickness as measured by ellipsometry. The TAA coating is adapted for secondary surface functionalization. The hydrophilic mPEG brushes can be grafted on the TAA coating to inhibit non-specific protein adsorption. A biotin probe can be immobilized on the TAA coating to promote specific binding with avidin. In addition, the TAA coating can be utilized for in situ reduction of silver ions to AgNPs. The resulting AgNP-loaded TAA coating can inhibit bacterial adhesion and prevent biofilm formation.

A Simple Drop-and-Dry Approach to Grass-Like Multifunctional Nanocoating on Flexible Cotton Fabrics Using In Situ-Generated Coating Solution Comprising Titanium-Oxo Clusters and Silver Nanoparticles.

Multifunctional nanocoatings have been of central importance in various technological fields, yet their fabrication, especially on flexible substrates, still remains a persistent challenge to date. We herein demonstrate a mild single-step drop-and-dry approach to the in situ growth of hierarchical grass-like nanostructures on flexible cotton fabrics. A precursor solution comprising titanium-oxo clusters [Ti18MnO30(OEt)20(MnPhen)3] (Phen = 1,10-phenanthroline) and AgNO3 is employed wherein Ag+ cations are in situ-reduced to silver nanoparticles (AgNPs). Drop-casting onto cotton fabrics under mild conditions induces the in situ growth of the heterogeneous grass-like assembly, and each constituent nanofibrous 'grass leaf' incorporates AgNPs both on the surface and embedded in the interior. The hierarchical morphology and heterogeneous composition of these grass-like nanostructures impart the coated cotton fabrics with enhanced antibacterial properties, robust hydrophobicity, and UV-blocking capability, which are features desired in textile materials but lacking in natural cotton.

Antimicrobial Peptide-Reduced Gold Nanoclusters with Charge-Reversal Moieties for Bacterial Targeting and Imaging.

To combat the increasing risk of infection by pathogenic bacteria, the new generation of antimicrobial agents is expected to exhibit nonmetabolic killing mechanisms, high potency and biocompatibility. In this work, cysteine-terminated antimicrobial peptide (AMP) was employed directly as a reducing ligand to synthesize AMP-coated gold nanoclusters (Au NCs), bypassing the use of other reagents which might interfere with the efficacy of the resulting NCs. In addition to the use of a biocompatible Au core, the primary amines of AMP coating were functionalized with anionic citraconyl moieties to further reduce cytotoxicity. The citraconyl amides could autocleave to re-expose the cationic amines at low pH. As a result, the AMP-coated Au NCs with citraconyl protection were stable and cytocompatible under physiological conditions as determined by fluorescamine, hemolytic, cytotoxicity, and in vivo toxicology studies, but would switch into a cationic bactericidal mode in an acidic environment commonly encountered at bacterial infection sites. Furthermore, the AMP-coated Au NCs system exhibited bacterial binding and photoluminescence features as determined by flow cytometry and confocal microscopy, which were useful for the detection and imaging of bacterial contamination. The AMP-coated Au NCs with citraconyl moieties therefore represent a "smart" design of pH-responsive antimicrobial agents that can serve multiple functions of bacterial detection, bacterial imaging, and anti-infection therapy.

The Pathway to Intelligence: Using Stimuli-Responsive Materials as Building Blocks for Constructing Smart and Functional Systems.

Systems that are intelligent have the ability to sense their surroundings, analyze, and respond accordingly. In nature, many biological systems are considered intelligent (e.g., humans, animals, and cells). For man-made systems, artificial intelligence is achieved by massively sophisticated electronic machines (e.g., computers and robots operated by advanced algorithms). On the other hand, freestanding materials (i.e., not tethered to a power supply) are usually passive and static. Hence, herein, the question is asked: can materials be fabricated so that they are intelligent? One promising approach is to use stimuli-responsive materials; these "smart" materials use the energy supplied by a stimulus available from the surrounding for performing a corresponding action. After decades of research, many interesting stimuli-responsive materials that can sense and perform smart functions have been developed. Classes of functions discussed include practical functions (e.g., targeting and motion), regulatory functions (e.g., self-regulation and amplification), and analytical processing functions (e.g., memory and computing). The pathway toward creating truly intelligent materials can involve incorporating a combination of these different types of functions into a single integrated system by using stimuli-responsive materials as the basic building blocks.

Chitosan-Based Peptidopolysaccharides as Cationic Antimicrobial Agents and Antibacterial Coatings.

The rapid spread of multidrug-resistant bacteria has called for effective antimicrobial agents which work on a more direct mechanism of killing. Cationic peptidopolysaccharides are developed in the present work to mimic the peptidoglycan structure of bacteria and to enhance the membrane-compromising bactericidal efficacy. Antimicrobial CysHHC10 peptide was grafted to the C-2 (amino) or C-6 (hydroxyl) position of chitosan backbone via thiol-maleimide "click" conjugation, utilizing the maleimidohexanoic linkers. The peptidopolysaccharide with primary amino backbone intact (CSOHHC) exhibited higher bactericidal activity toward Gram-positive and Gram-negative bacteria, in comparison to that with amino backbone grafted with the peptide (CSNHHC). Both peptidopolysaccharides also exhibited lower hemolytic activity and cytotoxicity than free CysHHC10 peptide due to the moderation effect contributed by the chitosan backbone. For targeting the Gram-positive bacteria in particular, the CSOHHC expressed 4- and 2-fold increases in hemo- and cytoselectivity, respectively, as compared to the CysHHC10 peptide. In an extended application, peptidopolysaccharide antibacterial coatings were formed via layer-by-layer assembly with tannic acid. The peptidopolysaccharide coatings readily killed the adhered bacteria upon contact while being cytocompatible by maintaining more than 60% viability for the adhered fibroblasts. Therefore, the peptidoglycan-mimetic peptidopolysaccharides are potential candidates for anti-infective drugs in biomedical applications.

Tailoring Polyelectrolyte Architecture To Promote Cell Growth and Inhibit Bacterial Adhesion.

An important challenge facing the application of implanted biomaterials for tissue engineering is the need to facilitate desirable tissue interactions with the implant while simultaneously inhibiting bacterial colonization, which can lead to implant-associated infection. In this study, we explore the relevance of the physical parameters of polyelectrolyte multilayers, such as surface charge, wettability, and stiffness, in tissue cell/surface and bacteria/surface interactions, and investigate the tuning of the multilayer architecture to differentially control such interactions. Polyions with different side-chain chemical structures were paired with polyethylenimine to assemble multilayers with parallel control over surface charge and wettability under controlled conditions. The multilayers can be successfully cross-linked to yield stiffer (the apparent Young's modulus was increased more than three times its original value) and more stable films while maintaining parallel control over surface charge and wettability. The initial adhesion and proliferation of 3T3 fibroblast cells were found to be strongly affected by surface charge and wettability on the non-cross-linked multilayers. On the other hand, these cells adhered and proliferated in a manner similar to those on the cross-linked multilayers (apparent Young's modulus ∼2 MPa), regardless of surface charge and wettability. In contrast, Staphylococcus aureus ( S. aureus) and Escherichia coli ( E. coli) adhesion was primarily controlled by surface charge and wettability on both cross-linked and non-cross-linked multilayers. In both cases, negative charge and hydrophilicity inhibited their adhesion. Thus, a surface coating with a relatively high degree of stiffness from covalent cross-linking coupled with negative surface charge and high wettability can serve as an efficient strategy to enhance host cell growth while resisting bacterial colonization.

Dominant Albumin-Surface Interactions under Independent Control of Surface Charge and Wettability.

Understanding protein adsorption behaviors on solid surfaces constitutes an important step toward development of efficacious and biocompatible medical devices. Both surface charge and wettability have been shown to influence protein adsorption attributes, including kinetics, quantities, deformation, and reversibility. However, determining the dominant interaction in these surface-induced phenomena is challenging because of the complexity of inter-related mechanisms at the liquid/solid interface. Herein, we reveal the dominant interfacial forces in these essential protein adsorption attributes under the influence of a combination of surface charge and wettability, using quartz crystal microbalance with dissipation monitoring and atomic force microscopy-based force spectroscopy on a series of model surfaces. These surfaces were fabricated via layer-by-layer assembly, which allowed two-dimensional control of surface charge and wettability with minimal cross-parameter dependency. We focused on a soft globular protein, bovine serum albumin (BSA), which is prone to conformational changes during adsorption. The information obtained from the two techniques shows that both surface charge and hydrophobicity can increase the protein-surface interaction forces and the adsorbed amount. However, surface hydrophobicity triggered a greater extent of deformation in the adsorbed BSA molecules, leading to more dehydration, spreading, and resistance to elution by ionic strength changes regardless of the surface charge. The role played by the surface charge in the adsorbed protein conformation and extent of desorption induced by changes in the ionic strength is secondary to that of surface hydrophobicity. These findings advance the understanding of how surface chemistry and properties can be tailored for directing protein-substrate interactions.

pH-Sensitive Zwitterionic Polymer as an Antimicrobial Agent with Effective Bacterial Targeting.

It is highly desirable to develop new and more potent biocompatible antimicrobial agents to reduce the increasing risk of bacterial infection worldwide. To address this problem, we prepared a smart pH-sensitive polymer, poly(N'-citraconyl-2-(3-aminopropyl-N,N-dimethylammonium)ethyl methacrylate), or P(CitAPDMAEMA), which can undergo change in functionality from a biocompatible zwitterionic polymer to an antimicrobial cationic polymer at acidic bacterial infection sites. The precursor polymer, poly(2-(3-aminopropyl-N,N-dimethylammonium)ethyl methacrylate) (P(APDMAEMA)), was first prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization, and then modified with citraconic anhydride to obtain the zwitterionic P(CitAPDMAEMA). P(CitAPDMAEMA) is zwitterionic at physiological pH and exhibits low hemotoxicity and good biocompatibility. However, P(CitAPDMAEMA) can change from neutral to cationic with decreasing pH because of the hydrolysis of citraconic amide under low pH conditions. This switch leads to pronounced bacteria binding of cationic P(CitAPDMAEMA) under acidic conditions of the infection sites and significantly inhibits the growth of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). These results indicate that P(CitAPDMAEMA) is potentially a new on-demand antimicrobial agent.