Designing Peptide/Graphene Hybrid Hydrogels through Fine-Tuning of Molecular Interactions. Wychowaniec Jacek K,Iliut Maria,Zhou Mi,Moffat Jonathan,Elsawy Mohamed A,Pinheiro Wagner A,Hoyland Judith A,Miller Aline F,Vijayaraghavan Aravind,Saiani Alberto Biomacromolecules A recent strategy that has emerged for the design of increasingly functional hydrogels is the incorporation of nanofillers in order to exploit their specific properties to either modify the performance of the hydrogel or add functionality. The emergence of carbon nanomaterials in particular has provided great opportunity for the use of graphene derivatives (GDs) in biomedical applications. The key challenge when designing hybrid materials is the understanding of the molecular interactions between the matrix (peptide nanofibers) and the nanofiller (here GDs) and how these affect the final properties of the bulk material. For the purpose of this work, three gelling β-sheet-forming, self-assembling peptides with varying physiochemical properties and five GDs with varying surface chemistries were chosen to formulate novel hybrid hydrogels. First the peptide hydrogels and the GDs were characterized; subsequently, the molecular interaction between peptides nanofibers and GDs were probed before formulating and mechanically characterizing the hybrid hydrogels. We show how the interplay between electrostatic interactions, which can be attractive or repulsive, and hydrophobic (and π-π in the case of peptide containing phenylalanine) interactions, which are always attractive, play a key role on the final properties of the hybrid hydrogels. The shear modulus of the hydrid hydrogels is shown to be related to the strength of fiber adhesion to the flakes, the overall hydrophobicity of the peptides, as well as the type of fibrillar network formed. Finally, the cytotoxicity of the hybrid hydrogel formed at pH 6 was also investigated by encapsulating and culturing human mesemchymal stem cells (hMSC) over 14 days. This work clearly shows how interactions between peptides and GDs can be used to tailor the mechanical properties of the resulting hydrogels, allowing the incorporation of GD nanofillers in a controlled way and opening the possibility to exploit their intrinsic properties to design novel hybrid peptide hydrogels for biomedical applications. 10.1021/acs.biomac.8b00333
    Fabrication of Chitosan-Reinforced Multifunctional Graphene Nanocomposite as Antibacterial Scaffolds for Hemorrhage Control and Wound-Healing Application. Choudhary Priyadarshani,Ramalingam Baskaran,Das Sujoy K ACS biomaterials science & engineering Accidents on battlefields and roads often lead to hemorrhage and uncontrolled bleeding. Hence, immediate hemorrhage control remains of great importance to reduce mortality and socioeconomic loss. Herein, nanobiocomposite scaffolds (film and sponge) have been fabricated for the first time through the incorporation of a graphene-silver-polycationic peptide (GAP) nanocomposite into chitosan (Cs). Ten different scaffolds viz. Cs, Cs-GAP25, Cs-GAP50, Cs-GAP75, and Cs-GAP100 were prepared in the form of films and sponges. Cs-GAP100 nanobiocomposite sponge exhibited excellent porosity, fluid absorption, and blood clotting capacity, whereas Cs-GAP100 nanobiocomposite film showed excellent mechanical strength and poor degradation property. The presence of graphene in GAP provided a unique mechanical property and prevented the natural degradation, whereas silver nanoparticles and polycationic peptide provided an efficient antimicrobial property to the scaffolds. The high surface area of graphene and the hydrophilic nature of the polycationic peptide also imparted high fluid and blood absorption capacity to Cs-GAP nanobiocomposite scaffolds. The in vitro whole blood clotting assay demonstrated that clotting efficacy improved with the concentration of GAP nanocomposite and Cs-GAP100 nanobiocomposite sponge significantly ( value <0.003) reduced the clotting time to 60 s, as compared to the pristine chitosan dressings. On the other side, the Cs-GAP100 nanobiocomposite film showed an excellent wound-healing property. The Cs-GAP100 nanobiocomposite demonstrated profound antibacterial activity against and . The intracellular reactive oxygen species (ROS) assay explained the interfacial interaction of Cs-GAP100 nanobiocomposite and bacterial cells, resulting in cell damage and finally cell death. The obtained information thus provided a novel safe-by-design concept for fabrication of Cs-GAP100 nanobiocomposite scaffolds and demonstrated potential development of antibacterial hemostatic and wound dressing in traumacare management. 10.1021/acsbiomaterials.0c00923
    Graphene oxide containing self-assembling peptide hybrid hydrogels as a potential 3D injectable cell delivery platform for intervertebral disc repair applications. Ligorio Cosimo,Zhou Mi,Wychowaniec Jacek K,Zhu Xinyi,Bartlam Cian,Miller Aline F,Vijayaraghavan Aravind,Hoyland Judith A,Saiani Alberto Acta biomaterialia Cell-based therapies have shown significant promise in tissue engineering with one key challenge being the delivery and retention of cells. As a result, significant efforts have been made in the past decade to design injectable biomaterials to host and deliver cells at injury sites. Intervertebral disc (IVD) degeneration, a major cause of back pain, is a particularly relevant example where a minimally-invasive cellular therapy could bring significant benefits specifically at the early stages of the disease, when a cell-driven process starts in the gelatinous core of the IVD, the nucleus pulposus (NP). In this present study we explore the use of graphene oxide (GO) as nano-filler for the reinforcement of FEFKFEFK (β-sheet forming self-assembling peptide) hydrogels. Our results confirm the presence of strong interactions between FEFKFEFK and GO flakes with the peptide coating and forming short thin fibrils on the surface of the flakes. These strong interactions were found to affect the bulk properties of hybrid hydrogels. At pH 4 electrostatic interactions between the peptide fibres and the peptide-coated GO flakes are thought to govern the final bulk properties of the hydrogels while at pH 7, after conditioning with cell culture media, electrostatic interactions are removed leaving the hydrophobic interactions to govern hydrogel final properties. The GO-F820 hybrid hydrogel, with mechanical properties similar to the NP, was shown to promote high cell viability and retained cell metabolic activity in 3D over the 7 days of culture and therefore shown to harbour significant potential as an injectable hydrogel scaffold for the in-vivo delivery of NP cells. STATEMENT OF SIGNIFICANCE: Short self-assembling peptide hydrogels (SAPHs) have attracted significant interest in recent years as they can mimic the natural extra-cellular matrix, holding significant promise for the ab initio design of cells' microenvironments. Recently the design of hybrid hydrogels for biomedical applications has been explored through the incorporation of specific nanofillers. In this study we exploited graphene oxide (GO) as nanofiller to design hybrid injectable 3Dscaffolds for the delivery of nucleus pulposus cells (NPCs) for intervertebral disc regeneration. Our work clearly shows the presence of strong interactions between peptide and GO, mimicking the mechanical properties of the NP tissue and promoting high cell viability and metabolic activity. These hybrid hydrogels therefore harbour significant potential as injectable scaffolds for the in vivo delivery of NPCs. 10.1016/j.actbio.2019.05.004
    Antimicrobial Peptide-Conjugated Graphene Oxide Membrane for Efficient Removal and Effective Killing of Multiple Drug Resistant Bacteria. Kanchanapally Rajashekhar,Viraka Nellore Bhanu Priya,Sinha Sudarson Sekhar,Pedraza Francisco,Jones Stacy J,Pramanik Avijit,Chavva Suhash Reddy,Tchounwou Christine,Shi Yongliang,Vangara Aruna,Sardar Dhiraj,Ray Paresh Chandra RSC advances According to the World Health Organization (WHO), multiple drug-resistant (MDR) bacterial infection is a top threat to human health. Since bacteria evolve to resist antibiotics faster than scientists can develop new classes of drugs, the development of new materials which can be used, not only for separation, but also for effective disinfection of drug resistant pathogens is urgent. Driven by this need, we report for the first time the development of a nisin antimicrobial peptide conjugated, three dimensional (3D) porous graphene oxide membrane for identification, effective separation, and complete disinfection of MDR methicillin-resistant (MRSA) pathogens from water. Experimental data show that due to the size differences, MRSA is captured by the porous membrane, allowing only water to pass through. SEM, TEM, and fluorescence images confirm that pathogens are captured by the membrane. RT-PCR data with colony counting indicate that almost 100% of can be removed and destroyed from the water sample using the developed membrane. Comparison of MDR killing data between nisin alone, the graphene oxide membrane and the nisin attached graphene oxide membrane demonstrate that the nisin antimicrobial peptide attached graphene oxide membrane can dramatically enhance the possibility of destroying MRSA via a synergestic effect due to the multimodal mechanism. 10.1039/C5RA01321F
    Adsorption mechanism of an antimicrobial peptide on carbonaceous surfaces: A molecular dynamics study. Roccatano Danilo,Sarukhanyan Edita,Zangi Ronen The Journal of chemical physics Peptides are versatile molecules with applications spanning from biotechnology to nanomedicine. They exhibit a good capability to unbundle carbon nanotubes (CNT) by improving their solubility in water. Furthermore, they are a powerful drug delivery system since they can easily be uptaken by living cells, and their high surface-to-volume ratio facilitates the adsorption of molecules of different natures. Therefore, understanding the interaction mechanism between peptides and CNT is important for designing novel therapeutical agents. In this paper, the mechanisms of the adsorption of antimicrobial peptide Cecropin A-Magainin 2 (CA-MA) on a graphene nanosheet (GNS) and on an ultra-short single-walled CNT are characterized using molecular dynamics simulations. The results show that the peptide coats both GNS and CNT surfaces through preferential contacts with aromatic side chains. The peptide packs compactly on the carbon surfaces where the polar and functionalizable Lys side chains protrude into the bulk solvent. It is shown that the adsorption is strongly correlated to the loss of the peptide helical structure. In the case of the CNT, the outer surface is significantly more accessible for adsorption. Nevertheless when the outer surface is already covered by other peptides, a spontaneous diffusion, via the amidated C-terminus into the interior of the CNT, was observed within 150 ns of simulation time. We found that this spontaneous insertion into the CNT interior can be controlled by the polarity of the entrance rim. For the positively charged CA-MA peptide studied, hydrogenated and fluorinated rims, respectively, hinder and promote the insertion. 10.1063/1.4975689