Structures in Other Domains The methodology of structural analysis discussed in this article has been applied beyond the narrow realm of natural language syntax that we have discussed in this article. Within the study of language, similar methods of analysis have been pervasively applied to the study of sounds (phonology), words (morphology), and meanings (semantics), yielding a range of of abstract structural representations whose properties bear considerable explanatory burden. There are a wealth of cases in each of these domains analogous to those discussed here, though space prevents us from going in these (see Akmajian, Demers, Farmer and Harnish 1995 for a traditional overview, and Jackendo 1994 for one more focused on connections with cognitive science). Additionally, these representations have shed substantial light on the processes of language acquisition and language change. It has been found that variation in the types of sentences that are used, whether during the course of children's acquisition of their native languages or in the centuries-long periods of linguistic change, are best characterized not as super cial and haphazard alterations, but rather in terms of parametric modi cations to the fundamental underlying grammatical rules and constraints. Moving outside the domain of language, one application of these same methods has been in the study of music cognition. Just as the representations of linguistic theory arise out of an attempt to model speakers' intuitions about well-formedness and possible meanings of the sentences of their

Structural analysis

Three-dimensional (3D) cell printing is a versatile technique enabling the creation of 3D constructs containing hydrogel and cells in the desired shape or pattern. Bioinks exhibiting appropriate mechanical properties and biological activities to support cell growth and/or differentiation toward a specific lineage play critical roles in 3D cell printing and tissue engineering applications. Herein, we explored alginate/graphene oxide (GO) composites as bioinks for their potential to improve printability, structural stability, and osteogenic activities for osteogenic tissue engineering applications. The addition of GO (0.05-1.0 mg mL-1) to 3% alginate significantly enhanced the printing performances of the alginate bioink. In addition, mesenchymal stem cells (MSCs) printed with alginate/GO showed good proliferation and higher survival in an oxidative stress environment. The 3D scaffolds printed with MSCs and alginate/GO demonstrated significantly enhanced osteogenic differentiation compared with those printed with MSCs and alginate. Overall, a bioink of 3% alginate and 0.5 mg mL-1 GO showed the most balanced characteristics in terms of printability, structural stability, and osteogenic induction of the printed MSCs. Alginate/GO composite bioinks will be useful for bioprinting research for various tissue engineering applications.

Graphene oxide/alginate composites as novel bioinks for three-dimensional mesenchymal stem cell printing and bone regeneration applications

3D bioprinting of graphene oxide-incorporated cell-laden bone mimicking scaffolds for promoting scaffold fidelity, osteogenic differentiation and mineralization.

Bacterial infections are a major threat to human health, exacerbated by increasing antibiotic resistance. These infections can result in tremendous morbidity and mortality, emphasizing the need to identify and treat pathogenic bacteria quickly and effectively. Recent developments in detection methods have focused on electrochemical, optical, and mass-based biosensors. Advances in these systems include implementing multifunctional materials, microfluidic sampling, and portable data-processing to improve sensitivity, specificity, and ease of operation. Concurrently, advances in antibacterial treatment have largely focused on targeted and responsive delivery for both antibiotics and antibiotic alternatives. Antibiotic alternatives described here include repurposed drugs, antimicrobial peptides and polymers, nucleic acids, small molecules, living systems, and bacteriophages. Finally, closed-loop therapies are combining advances in the fields of both detection and treatment. This review provides a comprehensive summary of the current trends in detection and treatment systems for bacterial infections.

Recent Innovations in Bacterial Infection Detection and Treatment.

Graphene and graphene derivatives (e.g., graphene oxide (GO)) have been incorporated into hydrogels to improve the properties (e.g., mechanical strength) of conventional hydrogels and/or develop new functions (e.g., electrical conductivity and drug loading/delivery). Unique molecular interactions between graphene derivatives and various small or macromolecules enable the fabrication of various functional hydrogels appropriate for different biomedical applications. In this mini-review, we highlight the recent progress in GO-incorporated hydrogels for biomedical applications while focusing on their specific uses as mechanically strong materials, electrically conductive scaffolds/electrodes, and high-performance drug delivery vehicles. Graphene derivatives (e.g., graphene oxide (GO)) have been incorporated in hydrogels to improve the properties (e.g., mechanical strength) of conventional hydrogels and/or develop new functions (e.g., electrical conductivity and drug loading/delivery) for various biomedical applications.

Graphene oxide-incorporated hydrogels for biomedical applications

Alginate-graphene oxide hydrogels with enhanced ionic tunability and chemomechanical stability for light-directed 3D printing

Intravascular catheter related bloodstream infections (CRBSIs) are a leading cause of hospital-acquired infections worldwide, resulting not only in the burden of cost and morbidity for patients but also in the over-consumption of medical resources for hospitals and health care organizations. In this study, a novel auranofin releasing antibacterial and antibiofilm polyurethane (PU) catheter coating was developed and investigated for future use in preventing CRBSIs. Auranofin is an antirheumatic drug with recently identified antimicrobial properties. The drug carrier, PU, acts as a barrier surrounding the antibacterial agent, auranofin, to extend the drug release profile and improve its long-term antibacterial and antibiofilm efficacy and potentially the length of catheter implantation within a patient. The PU+auranofin coatings developed here were found to be highly stretchable (exhibiting ~500% percent elongation), which is important for the compliance of the material on a flexible catheter. PU+auranofin coated catheters were able to inhibit the growth of methicillin-resistant Staphylococcus aureus (MRSA) for 8 to 26 days depending on the specific drug concentration utilized during the dip coating process. The PU+auranofin coated catheters were also able to completely inhibit MRSA biofilm formation in vitro, an effect that was not observed with auranofin or PU alone. Lastly, these coatings were found to be hemocompatible with human erythrocytes and maintain liver cell viability.

Auranofin releasing antibacterial and antibiofilm polyurethane intravascular catheter coatings

Hydrogels are used extensively in wound management. Many wounds are highly susceptible to infection and hydrogels can provide localized antibacterial delivery to treat and prevent this infection. There are several key considerations in designing antibacterial hydrogels for wound therapy, including preserving activity of encapsulated antibacterial agents, controlling drug release timescales and concentrations, and having the ability to conform to various wound configurations. In this work, we have used gellan, a U.S. Food and Drug Administration approved food additive, to develop antibiotic loaded hydrogels focusing on these criteria. These hydrogels were formed to exhibit a range of mechanical properties, which were investigated using oscillatory rheology. We denoted hydrogels formed using 1% w/v gellan and 1 mM CaCl2"ointment" hydrogels and those formed using 4% w/v gellan and 7 mM CaCl2"sheet" hydrogels. Vancomycin, a broad-spectrum antibiotic against Gram-positive bacteria, was encapsulated in these hydrogels both directly and/or in graphitized carbon black nanoparticles (CNPs). We found that vancomycin released from both sheet and ointment hydrogels at therapeutically effective concentrations over 9 days with CNPs and 6 days without CNPs. Applying the Ritger-Peppas and Peppas-Sahlin semi-empirical drug release models to sheet hydrogels, we determined that Fickian diffusion dominates release while case II relaxation also has a small contribution. The sheet hydrogels exhibited a larger overall release of the drug (83.6 ± 1.6% compared to 67.0 ± 2.6% for ointments), which was attributed to the larger swelling resulting from osmotic pressure differences between the hydrogel formulations and the release buffer. We also suggest that final drug release amounts are influenced by intermolecular interactions between vancomycin and gellan, which were observed via quartz crystal microbalance with dissipation monitoring. Lastly, we examined the potential for future in vivo translation. We demonstrated in vitro growth inhibition of Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus in the presence of these hydrogels, demonstrating that vancomycin activity is preserved upon encapsulation. We also showed that these hydrogels are non-toxic to important wound healing cells including fibroblasts and mesenchymal stem cells.

Tunable antibiotic delivery from gellan hydrogels

Probiotics might provide an alternative approach for the control of oral candidiasis. However, studies on the antifungal activity of probiotics in the oral cavity are based on the consumption of yogurt or other dietary products, and it is necessary to use appropriate biomaterials and specific strains to obtain probiotic formulations targeted for local oral administration. In this study, we impregnated gellan gum, a natural biopolymer used as a food additive, with a probiotic and investigated its antifungal activity against Candida albicansLactobacillus paracasei 28.4, a strain recently isolated from the oral cavity of a caries-free individual, was incorporated in several concentrations of gellan gum (0.6% to 1% [wt/vol]). All tested concentrations could incorporate L. paracasei cells while maintaining bacterial viability. Probiotic-gellan gum formulations were stable for 7 days when stored at room temperature or 4°C. Long-term storage of bacterium-impregnated gellan gum was achieved when L. paracasei 28.4 was lyophilized. The probiotic-gellan gum formulations provided a release of L. paracasei cells over 24 h that was sufficient to inhibit the growth of C. albicans, with effects dependent on the cell concentrations incorporated into gellan gum. The probiotic-gellan gum formulations also had inhibitory activity against Candida sp. biofilms by reducing the number of Candida sp. cells (P < 0.0001), decreasing the total biomass (P = 0.0003), and impairing hyphae formation (P = 0.0002), compared to the control group which received no treatment. Interestingly, a probiotic formulation of 1% (wt/vol) gellan gum provided an oral colonization of L. paracasei in mice with approximately 6 log CFU/ml after 10 days. This formulation inhibited C. albicans growth (P < 0.0001), prevented the development of candidiasis lesions (P = 0.0013), and suppressed inflammation (P = 0.0006) compared to the mice not treated in the microscopic analysis of the tongue dorsum. These results indicate that gellan gum is a promising biomaterial and can be used as a carrier system to promote oral colonization for probiotics that prevent oral candidiasis.

Shashank Shukla

Papers

Alginate-graphene oxide hydrogels with enhanced ionic tunability and chemomechanical stability for light-directed 3D printing

Auranofin releasing antibacterial and antibiofilm polyurethane intravascular catheter coatings

Tunable antibiotic delivery from gellan hydrogels

Development of Probiotic Formulations for Oral Candidiasis Prevention: Gellan Gum as a Carrier To Deliver Lactobacillus paracasei 28.4.

Effect of polymer and ion concentration on mechanical and drug release behavior of gellan hydrogels using factorial design