Polymethacrylate Hydrogels Research Articles

Triggered Release of Ampicillin from Metallic Implant Coatings for Combating Periprosthetic Infections.

Periprosthetic infections caused by Staphylococcus aureus (S. aureus) pose unique challenges in orthopedic surgeries, in part due to the bacterium's capacity to invade surrounding bone tissues besides forming recalcitrant biofilms on implant surfaces. We previously developed prophylactic implant coatings for the on-demand release of vancomycin, triggered by the cleavage of an oligonucleotide (Oligo) linker by micrococcal nuclease (MN) secreted by the Gram-positive bacterium, to eradicate S. aureus surrounding the implant in vitro and in vivo. Building upon this coating platform, here we explore the feasibility of extending the on-demand release to ampicillin, a broad-spectrum aminopenicillin β-lactam antibiotic that is more effective than vancomycin in killing Gram-negative bacteria that may accompany S. aureus infections. The amino group of ampicillin was successfully conjugated to the carboxyl end of an MN-sensitive Oligo covalently integrated in a polymethacrylate hydrogel coating applied to titanium alloy pins. The resultant Oligo-Ampicillin hydrogel coating released the β-lactam in the presence of S. aureus and successfully cleared nearby S. aureus in vitro. When the Oligo-Ampicillin-coated pin was delivered to a rat femoral canal inoculated with 1000 cfu S. aureus, it prevented periprosthetic infection with timely on-demand drug release. The clearance of the bacteria from the pin surface as well as surrounding tissue persisted over 3 months, with no local or systemic toxicity observed with the coating. The negatively charged Oligo fragment attached to ampicillin upon cleavage from the coating did diminish the antibiotic's potency against S. aureus and Escherichia coli (E. coli) to varying degrees, likely due to electrostatic repulsion by the anionic surfaces of the bacteria. Although the on-demand release of the β-lactam led to adequate killing of S. aureus but not E. coli in the presence of a mixture of the bacteria, strong inhibition of the colonization of the remaining E. coli on hydrogel coating was observed. These findings will inspire considerations of alternative broad-spectrum antibiotics, optimized drug conjugation, and Oligo linker engineering for more effective protection against polymicrobial periprosthetic infections.

Inherent Photodegradability of Polymethacrylate Hydrogels: Straightforward Access to Biocompatible Soft Microstructures

AbstractHydrogels are important functional materials useful for 3D cell culture, tissue engineering, 3D printing, drug delivery, sensors, or soft robotics. The ability to shape hydrogels into defined 3D structures, patterns, or particles is crucial for biomedical applications. Here, the rapid photodegradability of commonly used polymethacrylate hydrogels is demonstrated without the need to incorporate additional photolabile functionalities. Hydrogel degradation depths are quantified with respect to the irradiation time, light intensity, and chemical composition. It can be shown that these parameters can be utilized to control the photodegradation behavior of polymethacrylate hydrogels. The photodegradation kinetics, the change in mechanical properties of polymethacrylate hydrogels upon UV irradiation, as well as the photodegradation products are investigated. This approach is then exploited for microstructuring and patterning of hydrogels including hydrogel gradients as well as for the formation of hydrogel particles and hydrogel arrays of well‐defined shapes. Cell repellent but biocompatible hydrogel microwells are fabricated using this method and used to form arrays of cell spheroids. As this method is based on readily available and commonly used methacrylates and can be conducted using cheap UV light sources, it has vast potential to be applied by laboratories with various backgrounds and for diverse applications.

A comparative study of zwitterionic ligands-mediated mineralization and the potential of mineralized zwitterionic matrices for bone tissue engineering.

Cationic and anionic residues of the extracellular matrices (ECM) of bone play synergistic roles in recruiting precursor ions and templating the nucleation, growth and crystalline transformations of calcium apatite in natural biomineralization. We previously reported that zwitterionic sulfobetaine ligands can template extensive 3-dimensional (3-D) hydroxyapaptite (HA)-mineralization of photo-crosslinked polymethacrylatehydrogels. Here, we compared the potency of two other major zwitterionic ligands, phosphobetaine and carboxybetaine, with that of the sulfobetaine in mediating 3-D mineralization using the crosslinked polymethacrylate hydrogel platform. We confirmed that all three zwitterionic hydrogels were able to effectively template 3-D mineralization, supporting the general ability of zwitterions to mediate templated mineralization. Among them, however, sulfobetaine and phosphobetaine hydrogels templated denser 3-D mineralizationthan the carboxybetaine hydrogel, likely due to their higher free water fractions and better maintenance of zwitterionic nature throughout the pH-changes during the in vitro mineralization process. We further demonstrated that the extensively mineralized zwitterionic hydrogels could be exploited for efficient retention (e.g. 99% retention after 24-h incubation in PBS) of osteogenic growth factor recombinant bone morphogenetic protein-2 (rhBMP-2) and subsequent sustained local release with retained bioactivity. Combined with the excellent cytocompatibility of all three zwitterionic hydrogels and the significantly improved cell adhesive properties of their mineralized matrices, these materials could find promising applications in bone tissue engineering.

Corneal epithelialisation on surface-modified hydrogel implants

The objective was to investigate corneal re-epithelialisation of surface-modified polymethacrylate hydrogel implants in order to evaluate them as potential materials for an artificial cornea. Polymethacrylate hydrogels were modified with amines and then coated with different extracellular matrix proteins (collagen I, IV, laminin and fibronectin). The modified hydrogels were surgically implanted into bovine corneas maintained in a 3-D culture system for 5 days. The epithelial growth across the implant surface was evaluated using fluorescent, light and electron microscopy. Full epithelialisation was achieved on 1,4-diaminobutane-modified hydrogels after coating with collagen IV. Hydrogels modified with 1,4-diaminobutane but without further coating only showed partial re-epithelialisation. Hydrogels modified with other amines (1,2-diaminoethane or 1,3-diaminopropane) showed only partial re-epithelialisation; further coating with extracellular matrix proteins improved epithelialisation of these surfaces but did not result in complete re-epithelialisation. Evaluation of the corneas implanted with the 1,4-diaminobutane-modified hydrogels coated with collagen IV showed that the artificial corneas remain clear, integrate well and become covered by a healthy stratified epithelium. In conclusion the 1,4-diaminobutane surface-modified hydrogel coated with collagen IV supported the growth of a stable stratified epithelium. With further refinement this hydrogel has the potential to be used clinically for an artificial cornea.

Evolution process of polymethacrylate hydrogels investigated by rheological and dynamic light scattering techniques

Evolving gel formation processes of colloidal hydrogels derived from high solid-content polymethacrylate microemulsions have been studied using rheological and dynamic light scattering (DLS) techniques. The critical gel points, evaluated through oscillatory shear measurement and characterized by a single power-law exponent of G′ and G″ on the frequency (the power-law exponent, n = 0.36–0.65) were influenced more by the volume fraction of polymers than by the gelling temperature. Further topological fractal analysis and rheological studies suggested that reaction-limited cluster aggregation (RLCA) may dominate the aggregation behavior of polymer nanoparticles with the fractal dimension ( d f) = 1.8–2.2. The DLS results showed a fast relaxation mode with a single exponential decay followed by a slow one with a stretched exponential decay, which indicated that the gradual incorporation of polymer nanoparticles or clusters into the gel network leads to the maturity of the homogenous hydrogel network. Comparative studies on a series of polymethacrylate hydrogel systems with different hydrophilicities demonstrated that a slight hydrophilicity favors gel formation. The gelation mechanism was discussed based on the in-situ aggregation of nanoparticles as well as in terms of the colloidal instability of high solid-content nanolatex.

Mineralization of Synthetic Polymer Scaffolds: A Bottom-Up Approach for the Development of Artificial Bone

The controlled integration of organic and inorganic components confers natural bone with superior mechanical properties. Bone biogenesis is thought to occur by templated mineralization of hard apatite crystals by an elastic protein scaffold, a process we sought to emulate with synthetic biomimetic hydrogel polymers. Cross-linked polymethacrylamide and polymethacrylate hydrogels were functionalized with mineral-binding ligands and used to template the formation of hydroxyapatite. Strong adhesion between the organic and inorganic materials was achieved for hydrogels functionalized with either carboxylate or hydroxy ligands. The mineral-nucleating potential of hydroxyl groups identified here broadens the design parameters for synthetic bonelike composites and suggests a potential role for hydroxylated collagen proteins in bone mineralization.

Enthalpy of Swelling of Potassium Polyacrylate and Polymethacrylate Hydrogels. Evaluation of Excluded‐Volume Interaction

AbstractSummary: The enthalpy of swelling over the entire concentration range in potassium polyacrylate and polymethacrylate hydrogels with varying charge density was measured by means of isothermal Calvet microcalorimetry at 298 K. Concentration plots of the enthalpy of swelling at polymer volume fractions up to 50% were used for evaluation of Flory‐Huggins binary parameter of interaction. Apparent values of χ determined directly from experimental plots revealed extremely strong concentration dependence at high degrees of swelling. This was taken as evidence for the overlap of electrostatic and excluded‐volume interactions. The separate evaluation of these contributions to the enthalpy of swelling was performed using the recent theory developed for the enthalpy of dilution in semi‐dilute polyelectrolyte solutions. The mean value of the parameter χ over a wide range of swelling for the uncharged poly(acrylic acid) and poly(methacrylic acid) gel was found equal to 0.21 and −0.50 respectively. The ionization of the gel network due to the introduction of potassium salt residues resulted in the progressive decrease in the quality of the solvent. At 40–50% of ionization, the binary interaction parameter was about 2.8 both for potassium polyacrylate and polymethacrylate hydrogels. That value is much more than the critical value for liquid‐liquid phase separation in non‐electrolyte polymer solutions. magnified image

Synthesis of CuII‐complexed polymers and use as catalysts in the hydrolytic decontamination of Sarin nerve agent†

AbstractA range of polymer‐supported bidentate amine Cu II complexes have been synthesized based on linear polymers, crosslinked resins and hydrogels as precursor species. Linear styrene, acrylate and methacrylate structures have been examined along with reactive crosslinked resins derived from vinylbenzyl chloride, glycidyl methacrylate and methacrylic acid (Amberlite IRC‐50). Hydrogels based on hydroxyethyl methacrylate, hydroxyethyl acrylate and hydroxypropyl acrylate, each copolymerized with a diamine containing monomer, have also been prepared.Each Cu II‐complexed polymer has been assessed as a catalyst in the hydrolytic decomposition of the nerve agent, Sarin, as a possible strategy for developing self‐decontaminating materials and coatings for both personnel and equipment in the event of a nerve agent challenge in the field.Based on the measured half‐lives for hydrolysis of Sarin all of the polymer Cu II complexes show remarkable catalytic activity relative to the rate of the uncatalyzed hydrolysis reaction. The linear polymethacrylate‐based catalysts are the most active followed by the linear polystyrene‐based species, the macroporous polymethacrylates and the polystyrene resins. The polymethacrylate hydrogels are the least effective. It seems therefore that the hydrophilic/hydrophobic balance is important in controlling Sarin access to the catalytic sites, and this seems to be optimal in the linear polymethacrylate‐based catalysts. The results are discussed further in the context of the existing literature. Copyright © 2001 John Wiley & Sons, Ltd.