Substance P-Derived Extracellular-Matrix-Mimicking Peptide Hydrogel as a Cytocompatible Biomaterial Platform.

Self-assembled short peptide-based hydrogel platforms have become widely applicable biomedical therapeutic maneuvers for their soft, tunable architecture, which can influence cellular behavior and morphology to an inordinate extent. In this work, a short supramolecular hydrogelator peptide, substance P, has been designed and synthesized from the C terminus conserved "FFGLM" section of a biologically abundant neuropeptide by using a fusion approach. In addition, to incorporate a good hydrophobic-hydrophilic balance, the truncated pentapeptide segment was further C-terminally modified by the incorporation of an integrin-binding "RGD" motif. Thanks to its N-terminal Fmoc group, this octapeptide ensemble "FFGLMRGD" undergoes rapid self-assembly to give rise to an injectable, pH-responsive, hydrogel-based self-supporting platform that exhibited good cytocompatibility with the cultured mammalian cells under both 2D and 3D culture conditions without exerting any potent cytotoxic effect in a Live/Dead experiment. A rheological experiment demonstrated its hydrogel-like mechanical properties, including thixotropicity. The atomic force microscopy and field emission scanning electron microscopy images of the fabricated hydrogel show a tangled fibrous surface topography owing to the presence of the N-terminal Fmoc-FF residue. Furthermore, an in-vitro scratch assay performed on fibroblast cell lines confirmed the wound-ameliorating potency of this designed hydrogel; this substantiates its future therapeutic prospects.

Design of Cationic Lipids with Acetal Linkers: Conformational Preferences, Hydrolytic Stability, and High Drug-Loading Abilities.

Lipids are key constituents of numerous biomedical drug delivery technologies. Here, we present the design, synthesis and biophysical characterizations of a library of cationic lipids containing an acetal residue in their linker region. These cationic acetal lipids (CALs) were conveniently prepared through a trans-acetalization protocol from commercially available precursors. NMR studies highlighted the conformational rigidity at the acetal residue and the high hydrolytic stability of these CALs. Fluorescence anisotropy studies revealed that the CAL with a pyridinium headgroup (CAL1) formed highly cohesive vesicular aggregates in water. These structural and self-assembly features of the CAL1 allowed up to 196 % w/w loading of curcumin (Cur) as a representative hydrophobic drug. A reconstitutable formulation of Cur was obtained as a result, which could deliver the drug inside mammalian cells with very high efficiency. The hemocompatibility and cytocompatibility of CAL1 was significantly enhanced by creating a coating of polydopamine (PDA) onto its vesicular assemblies to produce hybrid lipid-polymer nanocapsules. This work demonstrates rapid access to the useful synthetic lipid formulations with high potential in drug and gene delivery applications.

Antibacterial and Cytocompatible pH-Responsive Peptide Hydrogel.

A short peptide, FHHF-11, was designed to change stiffness as a function of pH due to changing degree of protonation of histidines. As pH changes in the physiologically relevant range, G' was measured at 0 Pa (pH 6) and 50,000 Pa (pH 8). This peptide-based hydrogel is antimicrobial and cytocompatible with skin cells (fibroblasts). It was demonstrated that the incorporation of unnatural AzAla tryptophan analog residue improves the antimicrobial properties of the hydrogel. The material developed can have a practical application and be a paradigm shift in the approach to wound treatment, and it will improve healing outcomes for millions of patients each year.

Antibacterial and Cytocompatible: Combining Silver Nitrate with Strontium Acetate Increases the Therapeutic Window.

Microbial infection and insufficient tissue formation are considered to be the two main causes of dental implant failure. Novel studies have focused on designing dual-functional strategies to promote antibacterial properties and improve tissue cell response simultaneously. In this study, we investigated the antibacterial properties and cytocompatibility of silver nitrate (AgNO3) and strontium acetate (SrAc) in a mono-culture setup for dental application. Additionally, we defined the therapeutic window between the minimum inhibitory concentration against pathogenic bacteria and maximum cytocompatible dose in the case of combined applications in a co-culture setup. Antibacterial properties were screened using Aggregatibacter actinomycetemcomitans and cell response experiments were performed with osteoblastic cells (MC3T3) and fibroblastic cells (NIH3T3). The osteoinductive behavior was investigated separately on MC3T3 cells using alizarin red staining. A therapeutic window for AgNO3 as well as SrAc applications could be defined in the case of MC3T3 cells while the cytocompatibility of NIH3T3 cells was compromised for all concentrations with an antibacterial effect. However, the combined application of AgNO3/SrAc caused an enhanced antibacterial effect and opened a therapeutic window for both cell lines. Enhanced mineralization rates could be observed in cultures containing SrAc. In conclusion, we were able to demonstrate that adding SrAc to AgNO3 not only intensifies antibacterial properties but also exhibits bone inductive characteristics, thereby offering a promising strategy to combat peri-implantitis and at the same time improve osseointegration in implant therapy.

Fibrous Aggregates of Short Peptides Containing Two Distinct Aromatic Amino Acid Residues.

The aim of the study was the assessment of the ability of short peptides to form aggregates under physiological conditions. The dipeptides studied were derived from different aromatic amino acids (heteroaromatic peptides). Tripeptides were obtained from two distinct aromatic amino acids and cysteine or methionine residue in the C-terminal, N-terminal, or central position. The ability of the peptides to form fibrous aggregates under physiological conditions was evaluated using three independent methods: the Congo Red assay, the Thioflavin T assay, and microscopic examinations using normal and polarized light. Materials potentially useful for regenerative medicine were selected based on their cytotoxicity to the endothelial cell line EA.hy 926 and physicochemical properties of films formed by peptides. The required parameters of biocompatibility were fulfilled by H-PheCysTrp-OH, H-PheCysTyr-OH, H-PheTyrMet-OH, and H-TrpTyr-OH.

Development and characterization of Lyophilized Transparized Decellularized stroma as a replacement for living cornea in deep anterior lamellar keratoplasty.

Corneal disease is the second cause of blindness in developing countries, where the number of corneal grafts needed by far exceeds the number available. In industrialized countries, although corneas are generally available for keratoplasty, onto inflamed and vascularized host beds they are often rejected despite immune-suppression. A non-immunogenic, transparent, cytocompatible stroma is therefore required, which can be lyophilized for long-term conservation. Decellularization methods were tested on porcine corneal stromas before validation on human corneas. Decellularization and lyophilization led to opacification of the stroma, which could be reversed by soaking in 100% glycerol. Cell-depleted transparized stromas were then lyophilized (LTDC) to allow their long-term conservation and water content was measured. The ultrastructure of LTDC corneas was examined by transmission electron microscopy (TEM). Histocompatibility antigens were undetectable on LTDC stromas by antibody staining. Finally, cytocompatibility of LTDC stromas was demonstrated on an ex vivo model of anterior lamellar keratoplasty. Differential staining was used to monitor colonization of LTDC stromas by cells from the receiving cornea. Only SDS-based decellularization produced acellular porcine stromas. The lowest SDS concentration tested (0.1%) was validated on human corneas. Unlike lyophilized corneas, LTDC stromas without residual water, express no histocompatibility markers, although TEM revealed the presence of cellular debris in an ultrastructural arrangement of collagen fibers very close to that of native corneas. This structure is compatible with colonization by cells from the receiver cornea in an ex vivo lamellar graft model. Our procedure produced non-immunogenic, transparent stromas with conserved ultrastructure compatible with long-term conservation.

Search for Fibrous Aggregates Potentially Useful in Regenerative Medicine Formed under Physiological Conditions by Self-Assembling Short Peptides Containing Two Identical Aromatic Amino Acid Residues.

This study investigates the propensity of short peptides to self-organize and the influence of aggregates on cell cultures. The dipeptides were derived from both enantiomers of identical aromatic amino acids and tripeptides were prepared from two identical aromatic amino acids with one cysteine or methionine residue in the C-terminal, N-terminal, or central position. The formation or absence of fibrous structures under physiological conditions was established using Congo Red and Thioflavine T assays as well as by microscopic examination using normal and polarized light. The in vitro stability of the aggregates in buffered saline solution was assessed over 30 days. Materials with potential for use in regenerative medicine were selected based on the cytotoxicity of the peptides to the endothelial cell line EA.hy 926 and the wettability of the surfaces of the films, as well as using scanning electron microscopy. The criteria were fulfilled by H-dPhedPhe-OH, H-dCysdPhedPhe-OH, H-CysTyrTyr-OH, H-dPhedPhedCys-OH, H-TyrTyrMet-OH, and H-TyrMetTyr-OH. Our preliminary results suggest that the morphology and cell viability of L919 fibroblast cells do not depend on the stereochemistry of the self-organizing peptides.

Electrospun Cytocompatible Polycaprolactone Blend Composite with Enhanced Wettability for Bone Tissue Engineering.

Electrospinning is recently used in tissue engineering due to their excellent ability to mimic the structure of extra cellular matrix (ECM), a prerequisite for creating an optimal microenvironment for cell growth. Electrospun nanofibrous composite scaffolds consisting of polycaprolactone (PCL)/Poly(1,4-butylene adipate-co-polycaprolactam) (PBAPCL) blend with hydroxyapatite (HA) have been fabricated to enhance the wettability and osseointegrative properties. Fourier transform-infrared spectroscopy (FT-IR) confirmed molecular interactions of the polymer blend along with the presence of HA. X-ray diffraction analysis (XRD) indicated semi-crystalline nature of the mat and also the presence of HA in the composite mat. The morphology of the fibres, were analyzed using scanning electron microscopy (SEM) and the diameter was found to be in the range of 400­600 nm. The composite fibers were of larger diameter compared to their polymer counterparts. Improved wettability of the electrospun composite mat has been observed by contact angle analysis. In vitro cell culture studies by Live/Dead assay and MTT using human osteosarcoma (HOS) cells indicated the cytocompatible nature of electrospun mat which was further confirmed by cell adhesion using SEM and Actin-phalloidin staining. Addition of PBAPCL and HA to PCL have a beneficial effect on cell growth and proliferation thereby making the composite, a prospective scaffold for bone tissue engineering applications.

Tetracycline nanoparticles loaded calcium sulfate composite beads for periodontal management.

BACKGROUND: The objective of this study was to fabricate, characterize and evaluate in vitro, an injectable calcium sulfate bone cement beads loaded with an antibiotic nanoformulation, capable of delivering antibiotic locally for the treatment of periodontal disease. METHODS: Tetracycline nanoparticles (Tet NPs) were prepared using an ionic gelation method and characterized using DLS, SEM, and FTIR to determine size, morphology, stability and chemical interaction of the drug with the polymer. Further, calcium sulfate (CaSO4) control and CaSO4-Tet NP composite beads were prepared and characterized using SEM, FTIR and XRD. The drug release pattern, material properties and antibacterial activity were evaluated. In addition, protein adsorption, cytocompatibility and alkaline phosphatase activity of the CaSO4-Tet NP composite beads in comparison to the CaSO4 control were analyzed. RESULTS: Tet NPs showed a size range of 130±20nm and the entrapment efficiency calculated was 89%. The composite beads showed sustained drug release pattern. Further the drug release data was fitted into various kinetic models wherein the Higuchi model showed higher correlation value (R(2)=0.9279) as compared to other kinetic models. The composite beads showed antibacterial activity against Staphylococcus aureus and Escherichia coli. The presence of Tet NPs in the composite bead didn't alter its cytocompatibility. In addition, the composite beads enhanced the ALP activity of hPDL cells. CONCLUSIONS: The antibacterial and cytocompatible CaSO4-Tet NP composite beads could be beneficial in periodontal management to reduce the bacterial load at the infection site. GENERAL SIGNIFICANCE: Tet NPs would deliver antibiotic locally at the infection site and the calcium sulfate cement, would itself facilitate tissue regeneration.

Natural Polymer-Polyphenol Bioadhesive Coacervate with Stable Wet Adhesion, Antibacterial Activity, and On-Demand Detachment.

Medical adhesives are emerging as an important clinical tool as adjuvants for sutures and staples in wound closure and healing and in the achievement of hemostasis. However, clinical adhesives combining cytocompatibility, as well as strong and stable adhesion in physiological conditions, are still in demand. Herein, a mussel-inspired strategy is explored to produce adhesive coacervates using tannic acid (TA) and methacrylate pullulan (PUL-MA). TA|PUL-MA coacervates mainly comprise van der Waals forces and hydrophobic interactions. The methacrylic groups in the PUL backbone increase the number of interactions in the adhesives matrix, resulting in enhanced cohesion and adhesion strength (72.7 Jm-2), compared to the non-methacrylated coacervate. The adhesive properties are kept in physiologic-mimetic solutions (72.8 Jm-2) for 72 h. The photopolymerization of TA|PUL-MA enables the on-demand detachment of the adhesive. The poor cytocompatibility associated with the use of phenolic groups is here circumvented by mixing reactive oxygen species-degrading enzyme in the adhesive coacervate. This addition does not hamper the adhesive character of the materials, nor their anti-microbial or hemostatic properties. This affordable and straightforward methodology, together with the tailorable adhesivity even in wet environments, high cytocompatibility, and anti-bacterial activity, enables foresee TA|PUL-MA as a promising ready-to-use bioadhesive for biomedical applications.

A grafting approach for nisin-chitosan bio-based antibacterial films: preparation and characterization.

Nisin is a bacteriocin produced by Gram-positive lactic acid bacterium,Lactococcus lactisand currently recognized in the Generally Recognized as Safe (GRAS) category due to its non-toxicity. Herein, nisin has been grafted to chitosan structure to obtain natural bio-active films with enhanced antibacterial activity. Grafting was performed using ethyl ester lysine diisocyanate and dimer fatty acid-based diisocyanate (DDI); two different close to fully bio-based diisocyanates and Disuccinimidyl suberate; a homo-bifunctional molecule acting as a crosslinker between amino groups. The grafting process allowed the chemical immobilization of nisin to chitosan structure. Physicochemical characterization studies showed the successful grafting of nisin. The antibacterial activity againstStaphylococcus aureuswas evident for all nisin modified chitosan films and best pronounced when DDI was used as a crosslinker with a maximum zone of inhibition of ∼13 mm. All nisin grafted chitosan films were cytocompatible and the cell viability of L929 fibroblasts were >80% pointing out the non-toxic structure. Considering the results of the presented study, bio-based diisocyanates and homo-bifunctional crosslinkers are effective molecules in synthesis of nisin grafted chitosan structures and the new chitosan based antibacterial biopolymers obtained after nisin modification come forward as promising non-toxic and bioactive candidates to be applied in medical devices, implants, and various food coating products.

Tuning thermoresponsive properties of carboxymethyl cellulose (CMC)-agarose composite bioinks to fabricate complex 3D constructs for regenerative medicine.

3D bioprinting has emerged as a viable tool to fabricate 3D tissue constructs with high precision using various bioinks which offer instantaneous gelation, shape fidelity, and cytocompatibility. Among various bioinks, cellulose is the most abundantly available natural polymer & widely used as bioink for 3D bioprinting applications. To mitigate the demanding crosslinking needs of cellulose, it is frequently chemically modified or blended with other polymers to develop stable hydrogels. In this study, we have developed a thermoresponsive, composite bioink using carboxymethyl cellulose (CMC) and agarose in different ratios (9:1, 8:2, 7:3, 6:4, and 5:5). Among the tested combinations, the 5:5 ratio showed better gel formation at 37 °C and were further characterized for physicochemical properties. Cytocompatibility was assessed by in vitro extract cytotoxicity assay (ISO 10993-5) using skin fibroblasts cells. CMC-agarose (5:5) bioink was successfully used to fabricate complex 3D structures through extrusion bioprinting and maintained over 80 % cell viability over seven days. Finally, in vivo studies using rat full-thickness wounds showed the potential of CMC-agarose bulk and bioprinted gels in promoting skin regeneration. These results indicate the cytocompatibility and suitability of CMC-agarose bioinks for tissue engineering and 3D bioprinting applications.

Hydrogels dressings based on guar gum and chitosan: Inherent action against resistant bacteria and fast wound closure.

Hydrogels made with depolymerized guar gum, oxidized with theoretical oxidation degrees of 20, 35 and 50 %, were obtained via Schiff's base reaction with N-succinyl chitosan. The materials obtained were subjected to characterization by FT-IR, rheology, swelling, degradation, and morphology. Additionally, their gelation time categorized all three hydrogels as injectable. The materials' swelling degrees in Phosphate-Buffered Saline (PBS) were in the range of 26-35 g of fluid/g gel and their pore size distribution was heterogeneous, with pores varying from 67 to 93 µm. All hydrogels degraded in PBS solution, but maintained around 40 % of their initial mass after 28 days, which was more than enough time for wound healing. The biomaterials were also flexible, self-repairing, adhesive and cytocompatible and presented intrinsic actions, regardless of the presence of additives or antibiotics, against gram-positive (Staphylococcus aureus, Staphylococcus epidermidis) and gram-negative bacteria (Escherichia coli). However, the most pronounced bactericidal effect was against resistant Staphylococcus aureus - MRSA. In vivo assays, performed with 50 % oxidized gum gel, demonstrated that this material exerted anti-inflammatory effects, accelerating the healing process and restoring tissues by approximately 99 % within 14 days. In conclusion, these hydrogels have unique characteristics, making them excellent candidates for wound-healing dressings.

Thermally and Photothermally Triggered Cytocompatible Triple-Shape-Memory Polymer Based on a Graphene Oxide-Containing Poly(ε-caprolactone) and Acrylate Composite.

Triple-shape-memory polymers (triple-SMPs) are a class of polymers capable of fixing two temporary shapes and recovering sequentially from the first temporary shape to the second temporary shape and, last, to the permanent shape. To accomplish a sequential shape change, a triple-SMP must have two separate shape-fixing mechanisms triggerable by distinct stimuli. Despite the biomedical potential of triple-SMPs, a triple-SMP that with cells present can undergo two different shape changes via two distinct cytocompatible triggers has not previously been demonstrated. Here, we report the design and characterization of a cytocompatible triple-SMP material that responds separately to thermal and light triggers to undergo two distinct shape changes under cytocompatible conditions. Tandem triggering was achieved via a photothermally triggered component, comprising poly(ε-caprolactone) (PCL) fibers with graphene oxide (GO) particles physically attached, embedded in a thermally triggered component, comprising a tert-butyl acrylate-butyl acrylate (tBA-BA) matrix. The material was characterized in terms of thermal properties, surface morphology, shape-memory performance, and cytocompatibility during shape change. Collectively, the results demonstrate cytocompatible triple-shape behavior with a relatively larger thermal shape change (an average of 20.4 ± 4.2% strain recovered for all PCL-containing groups) followed by a smaller photothermal shape change (an average of 3.5 ± 0.8% strain recovered for all PCL-GO-containing groups; samples without GO showed no recovery) with greater than 95% cell viability on the triple-SMP materials, establishing the feasibility of triple-shape memory to be incorporated into biomedical devices and strategies.

New Photocrosslinked 3D Foamed Scaffolds Based on GelMA Copolymers: Potential Application in Bone Tissue Engineering.

The production of customized polymeric hydrogels in the form of 3D scaffolds with application in bone tissue engineering is currently a topic of great interest. Based on gelatin methacryloyl (GelMa) as one of the most popular used biomaterials, GelMa with two different methacryloylation degrees (DM) was obtained, to achieve crosslinked polymer networks by photoinitiated radical polymerization. In this work, we present the obtention of new 3D foamed scaffolds based on ternary copolymers of GelMa with vinylpyrrolidone (VP) and 2-hydroxyethylmethacrylate (HEMA). All biopolymers obtained in this work were characterized by infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA), whose results confirm the presence of all copolymers in the crosslinked biomaterial. In addition, scanning electron microscopy (SEM) pictures were obtained verifying the presence of the porosity created by freeze-drying process. In addition, the variation in its swelling degree and its enzymatic degradation in vitro was analyzed as a function of the different copolymers obtained. This has allowed us to observe good control of the variation in these properties described above in a simple way by varying the composition of the different comonomers used. Finally, with these concepts in mind, biopolymers obtained were tested through assessment of several biological parameters such as cell viability and differentiation with MC3T3-E1 pre-osteoblastic cell line. Results obtained show that these biopolymers maintain good results in terms of cell viability and differentiation, along with tunable properties in terms of hydrophilic character, mechanical properties and enzymatic degradation.

Tailoring the Electron Trapping Effect of a Biocompatible Triboelectric Hydrogel by Graphene Oxide Incorporation towards Self-Powered Medical Electronics.

Triboelectric nanogenerators (TENGs) are associated with several drawbacks that limit their application in the biomedical field, including toxicity, thrombogenicity, and poor performance in the presence of fluids. By proposing the use of a hemo/biocompatible hydrogel, poly(2-hydroxyethyl methacrylate) (pHEMA), this study bypasses these barriers. In contact-separation mode, using polytetrafluoroethylene (PTFE) as a reference, pHEMA generates an output of 100.0 V, under an open circuit, 4.7 µA, and 0.68 W/m2 for an internal resistance of 10 MΩ. Our findings unveil that graphene oxide (GO) can be used to tune pHEMA's triboelectric properties in a concentration-dependent manner. At the lowest measured concentration (0.2% GO), the generated outputs increase to 194.5 V, 5.3 µA, and 1.28 W/m2 due to the observed increase in pHEMA's surface roughness, which expands the contact area. Triboelectric performance starts to decrease as GO concentration increases, plateauing at 11% volumetric, where the output is 51 V, 1.76 µA, and 0.17 W/m2 less than pHEMA's. Increases in internal resistance, from 14 ΩM to greater than 470 ΩM, ζ-potential, from -7.3 to -0.4 mV, and open-circuit characteristic charge decay periods, from 90 to 120 ms, are all observed in conjunction with this phenomenon, which points to GO function as an electron trapping site in pHEMA's matrix. All of the composites can charge a 10 µF capacitor in 200 s, producing a voltage between 0.25 and 3.5 V and allowing the operation of at least 20 LEDs. The triboelectric output was largely steady throughout the 3.33 h durability test. Voltage decreases by 38% due to contact-separation frequency, whereas current increases by 77%. In terms of pressure, it appears to have little effect on voltage but boosts current output by 42%. Finally, pHEMA and pHEMA/GO extracts were cytocompatible toward fibroblasts. According to these results, pHEMA has a significant potential to function as a biomaterial to create bio/hemocompatible TENGs and GO to precisely control its triboelectric outputs.

Basic structure and cytocompatibility of giant membrane vesicles derived from paraformaldehyde-exposed human cells.

Exposure of cultured mammalian cells to paraformaldehyde (PFA) is an effective approach to induce membrane blebs, which is followed by their detachment from the cellular cortex to yield giant membrane vesicles in extracellular spaces. Although PFA-induced giant vesicles have attracted significant interest in the field of cell membrane dynamics, their biochemical components and cytocompatibility remain largely unknown. In this report, we exposed human cervical cancer HeLa cells to PFA under metal-free buffer conditions to produce giant vesicles. We analyzed the components and structure of the purified PFA-induced giant vesicles. Co-culturing PFA-induced giant vesicles with exponentially growing HeLa cells resulted in docking of a significant number of the giant vesicles to the cell surface with seemingly no cytotoxicity. Intriguingly, we found that pre-treatment of HeLa cells with peptide-N-glycosidase and neuraminidase was effective in facilitating cellular uptake of constituents residing inside the vesicles. The results revealed further details about the effect of PFA on cell membranes and provide insights for studying the interaction between PFA-induced giant vesicles and cultured cells.

Antibacterial activity, cytocompatibility, and thermomechanical stability of Ti40Zr10Cu36Pd14 bulk metallic glass.

This paper envisions Ti40Zr10Cu36Pd14 bulk metallic glass as an oral implant material and evaluates its antibacterial performance in the inhabitation of oral biofilm formation in comparison with the gold standard Ti-6Al-4V implant material. Metallic glasses are superior in terms of biocorrosion and have a reduced stress shielding effect compared with their crystalline counterparts. Dynamic mechanical and thermal expansion analyses on Ti40Zr10Cu36Pd14 show that these materials can be thermomechanically shaped into implants. Static water contact angle measurement on samples' surface shows an increased surface wettability on the Ti-6Al-4V surface after 48 â€‹h incubation in the water while the contact angle remains constant for Ti40Zr10Cu36Pd14. Further, high-resolution transmission and scanning transmission electron microscopy analysis have revealed that Ti40Zr10Cu36Pd14 interior is fully amorphous, while a 15 â€‹nm surface oxide is formed on its surface and assigned as copper oxide. Unlike titanium oxide formed on Ti-6Al-4V, copper oxide is hydrophobic, and its formation reduces surface wettability. Further surface analysis by X-ray photoelectron spectroscopy confirmed the presence of copper oxide on the surface. Metallic glasses cytocompatibility was first demonstrated towards human gingival fibroblasts, and then the antibacterial properties were verified towards the oral pathogen Aggregatibacter actinomycetemcomitans responsible for oral biofilm formation. After 24 â€‹h of direct infection, metallic glasses reported a >70% reduction of bacteria viability and the number of viable colonies was reduced by ∼8 times, as shown by the colony-forming unit count. Field emission scanning electron microscopy and fluorescent images confirmed the lower surface colonization of metallic glasses in comparison with controls. Finally, oral biofilm obtained from healthy volunteers was cultivated onto specimens' surface, and proteomics was applied to study the surface property impact on species composition within the oral plaque.

Biomimetic sharkskin surfaces with antibacterial, cytocompatible, and drug delivery properties.

Fighting with the infection is one of the most challenging and costly burdens of the healthcare system. Several types of antibiotics and antibacterial agents have been designed and used in combating this dilemma. Nevertheless, the overuse of drugs and the difficulties of proper delivery have led to the development of drug-resistance in many species of bacteria which has reduced the efficacy of antibiotics. Furthermore, localized delivery of these drugs can be more effective in eliminating biomaterial surface-associated infection compared to systemic administration. This type of infection occurs mostly by the formation of a bacterial biofilm layer on the surface of the implantable biomaterial which is the interface between the biomaterial and the tissue. Sharkskin topography is known for its antibacterial properties due to its unique pattern. Herein, antibacterial properties and drug release potentials of sharkskin mimicked chitosan membranes are investigated with the aim of studying the impact of this topography in reducing bacterial biofilm formation on drug-loaded polymeric membranes. Ampicillin sodium salt and caffeic acid phenethyl ester (CAPE) loaded chitosan (CH) membranes were fabricated. Gram-positive Staphylococcus aureus bacteria strain is used in antibacterial experiments, and human dermal fibroblast (HDFa) and keratinocyte (HaCaT) cells were used as model cell lines in cytocompatibility tests. Drug release, bacterial biofilm growth, and swelling ratio test results show the superiority of sharkskin topography in controlling the rate of drug release as well as considerably reducing bacterial biofilm formation. Furthermore, it was established that 2.5 mg mL-1 Amp content along with 500 µM CAPE yield in maximum antibacterial effect while not having cytotoxic effects on mammalian cells. Fabricated sharkskin mimicked drug-loaded membrane, which utilizes the combination of antibacterial compounds and antibacterial surface topography, also acts as an effective carrier for high concentrations of drugs.

Injectable, Pore-Forming, Perfusable Double-Network Hydrogels Resilient to Extreme Biomechanical Stimulations.

Biological tissues hinge on blood perfusion and mechanical toughness to function. Injectable hydrogels that possess both high permeability and toughness have profound impacts on regenerative medicine but remain a long-standing challenge. To address this issue, injectable, pore-forming double-network hydrogels are fabricated by orchestrating stepwise gelation and phase separation processes. The interconnected pores of the resulting hydrogels enable direct medium perfusion through organ-sized matrices. The hydrogels are amenable to cell encapsulation and delivery while promoting cell proliferation and spreading. They are also pore insensitive, tough, and fatigue resistant. When tested in biomimetic perfusion bioreactors, the hydrogels maintain physical integrity under prolonged, high-frequency biomechanical stimulations (>6000 000 cycles at 120 Hz). The excellent biomechanical performance suggests the great potential of the new injectable hydrogel technology for repairing mechanically dynamic tissues, such as vocal folds, and other applications, such as tissue engineering, biofabrication, organs-on-chips, drug delivery, and disease modeling.