Graphene@Curcumin-Copper Paintable Coatings for the Prevention of Nosocomial Microbial Infection.

The rise of antimicrobial resistance has brought into focus the urgent need for the next generation of antimicrobial coating. Specifically, the coating of suitable antimicrobial nanomaterials on contact surfaces seems to be an effective method for the disinfection/contact killing of microorganisms. In this study, the antimicrobial coatings of graphene@curcumin-copper (GN@CR-Cu) were prepared using a chemical synthesis methodology. Thus, the prepared GN@CR-Cu slurry was successfully coated on different contact surfaces, and subsequently, the GO in the composite was reduced to graphene (GN) by low-temperature heating/sunlight exposure. Scanning electron microscopy was used to characterize the coated GN@CR-Cu for the coating properties, X-ray photon scattering were used for structural characterization and material confirmation. From the morphological analysis, it was seen that CR and Cu were uniformly distributed throughout the GN network. The nanocomposite coating showed antimicrobial properties by contact-killing mechanisms, which was confirmed by zone inhibition and scanning electron microscopy. The materials showed maximum antibacterial activity against E. coli (24 ± 0.50 mm) followed by P. aeruginosa (18 ± 0.25 mm) at 25 µg/mL spot inoculation on the solid media plate, and a similar trend was observed in the minimum inhibition concentration (80 µg/mL) and bactericidal concentration (160 µg/mL) in liquid media. The synthesized materials showed excellent activity against E. coli and P. aeruginosa. These materials, when coated on different contact surfaces such medical devices, might significantly reduce the risk of nosocomial infection.

Oxygen-Generating Cryogels Restore T Cell Mediated Cytotoxicity in Hypoxic Tumors.

Solid tumors are protected from antitumor immune responses due to their hypoxic microenvironments. Weakening hypoxia-driven immunosuppression by hyperoxic breathing of 60% oxygen has shown to be effective in unleashing antitumor immune cells against solid tumors. However, efficacy of systemic oxygenation is limited against solid tumors outside of lungs and has been associated with unwanted side effects. As a result, it is essential to develop targeted oxygenation alternatives to weaken tumor hypoxia as novel approaches to restore immune responses against cancer. Herein, we report on injectable oxygen-generating cryogels (O2-cryogels) to reverse tumor-induced hypoxia. These macroporous biomaterials were designed to locally deliver oxygen, inhibit the expression of hypoxia-inducible genes in hypoxic melanoma cells, and reduce the accumulation of immunosuppressive extracellular adenosine. Our data show that O2-cryogels enhance T cell-mediated secretion of cytotoxic proteins, restoring the killing ability of tumor-specific CTLs, both in vitro and in vivo. In summary, O2-cryogels provide a unique and safe platform to supply oxygen as a co-adjuvant in hypoxic tumors and have the potential to improve cancer immunotherapies.

Injectable Lignin-co-Gelatin Cryogels with Antioxidant and Antibacterial Properties for Biomedical Applications.

For several biomedical applications, it is essential to develop novel bioactive materials. Such biomaterials could potentially improve wound healing, prevent infections, or be used in immunoengineering. For example, bioactive materials that reduce oxidative stress without relying on antibiotics and other drugs could be beneficial. Hydrogel-based biomaterials, especially those derived from natural polymers, have been regarded as one of the most promising scaffolds for biomedical research. These multifunctional scaffolds can exhibit high water adsorption capacity, biocompatibility, and biomechanical properties that can match native tissues. Cryogels are a special type of hydrogels in which polymers are cross-linked around ice crystals. As a result, cryogels exhibit unique physical features, including a macroporous and interconnected network, flexibility, shape-memory properties, and syringe injectability. Herein, we developed a multifunctional, i.e., antibacterial, antioxidant, and injectable cryogel by combining lignin with gelatin. The cryogel with 0.2% lignin showed a compressive modulus of 25 kPa and a compressive stress of 140 kPa at 80% strain, which is, respectively, 1.8 and 7 times higher than those of the pure gelatin cryogels. Meanwhile, such a cryogel formulation could completely recover its shape after compression up to 90% and was needle-injectable. Additionally, the lignin-co-gelatin cryogel with 0.1-0.2 lignin showed 8-10 mm of inhibition zone against the most common surgical site infection-associated pathogenic bacteria. Furthermore, lignin-co-gelatin cryogel was found to scavenge free radicals and have good cytocompatibility, and the cryogels with up to 0.2% lignin minimally activate naïve mouse bone marrow-derived dendritic cells. Overall, the current approach shows great promise for the design of bioresource-based multifunctional cryogels for a wide range of biomedical applications.

Hybrid Paper-Plastic Microchip for Flexible and High-Performance Point-of-Care Diagnostics.

A low-cost and easy-to-fabricate microchip remains a key challenge for the development of true point-of-care (POC) diagnostics. Cellulose paper and plastic are thin, light, flexible, and abundant raw materials, which make them excellent substrates for mass production of POC devices. Herein, a hybrid paper-plastic microchip (PPMC) is developed, which can be used for both single and multiplexed detection of different targets, providing flexibility in the design and fabrication of the microchip. The developed PPMC with printed electronics is evaluated for sensitive and reliable detection of a broad range of targets, such as liver and colon cancer protein biomarkers, intact Zika virus, and human papillomavirus nucleic acid amplicons. The presented approach allows a highly specific detection of the tested targets with detection limits as low as 102 ng mL-1 for protein biomarkers, 103 particle per milliliter for virus particles, and 102 copies per microliter for a target nucleic acid. This approach can potentially be considered for the development of inexpensive and stable POC microchip diagnostics and is suitable for the detection of a wide range of microbial infections and cancer biomarkers.

Study of Electrospinning Parameters and Collection Methods on Size Distribution and Orientation of PLA/PBS Hybrid Fiber Using Digital Image Processing.

The Canny Edge-Based Distance Transform and Hough Transform algorithms were successfully implemented to analyze the size distribution and the orientation of the electrospun PLA/PBS hybrid fiber. The effect of polymer concentration, voltage, feed rate and needle-collector distance were studied. It was found that feed rate of 0.5 ml/h and needle-collector distance of 12 cm is required to generate smooth and uniform hybrid fibers in the smallest size electrospinning with 6 wt.% polymer at voltage of 20 kV. The stationary flat collector with a swaying needle and fast rotating drum disc with a stationary needle were used for the fiber alignment. In order to improve the size distribution and the orientation of the hybrid fibers it is proposed that the fibers should be collected on the rotary drum disc at 700 rpm or higher speed.

A Comprehensive Review of Stem Cells for Cartilage Regeneration in Osteoarthritis.

Osteoarthritis (OA) is an age related joint disease associated with degeneration and loss of articular cartilage. Consequently, OA patients suffer from chronic joint pain and disability. Weight bearing joints and joints that undergo repetitive stress and excessive 'wear and tear' are particularly prone to developing OA. Cartilage has a poor regenerative capacity and current pharmacological agents only provide symptomatic pain relief. OA patients that respond poorly to conventional therapies are ultimately treated with surgical procedures to promote cartilage repair by implantation of artificial joint structures (arthroplasty) or total joint replacement (TJR). In the last two decades, stem cells derived from various tissues with varying differentiation and tissue regeneration potential have been used for the treatment of OA either alone or in combination with natural or synthetic scaffolds to aid cartilage repair. Although stem cells can be differentiated into chondrocytes in vitro or aid cartilage regeneration in vivo, their potential for OA management remains limited as cartilage regenerated by stem cells fails to fully recapitulate the structural and biomechanical properties of the native tissue. Efficient tissue regeneration remains elusive despite the simple design of cartilage, which unlike most other tissues is avascular and aneural, consisting of a single cell type. In this article, we have comprehensively reviewed the types of stem cells that have been proposed or tested for the management of OA, their potential efficacy as well as their limitations. We also touch on the role of biomaterials in cartilage tissue engineering and examine the prospects for their use in cell-based therapies.

Advances in Candida detection platforms for clinical and point-of-care applications.

Invasive candidiasis remains one of the most serious community and healthcare-acquired infections worldwide. Conventional Candida detection methods based on blood and plate culture are time-consuming and require at least 2-4 days to identify various Candida species. Despite considerable advances for candidiasis detection, the development of simple, compact and portable point-of-care diagnostics for rapid and precise testing that automatically performs cell lysis, nucleic acid extraction, purification and detection still remains a challenge. Here, we systematically review most prominent conventional and nonconventional techniques for the detection of various Candida species, including Candida staining, blood culture, serological testing and nucleic acid-based analysis. We also discuss the most advanced lab on a chip devices for candida detection.

Mesenchymal stem cells: Identification, phenotypic characterization, biological properties and potential for regenerative medicine through biomaterial micro-engineering of their niche.

Mesenchymal stem cells (MSCs) are multipotent stem cells. Although they were originally identified in bone marrow and described as 'marrow stromal cells', they have since been identified in many other anatomical locations in the body. MSCs can be isolated from bone marrow, adipose tissue, umbilical cord and other tissues but the richest tissue source of MSCs is fat. Since they are adherent to plastic, they may be expanded in vitro. MSCs have a distinct morphology and express a specific set of CD (cluster of differentiation) molecules. The phenotypic pattern for the identification of MSCs cells requires expression of CD73, CD90, and CD105 and lack of CD34, CD45, and HLA-DR antigens. Under appropriate micro-environmental conditions MSCs can proliferate and give rise to other cell types. Therefore, they are ideally suited for the treatment of systemic inflammatory and autoimmune conditions. They have also been implicated as key players in regenerating injured tissue following injury and trauma. MSC populations isolated from adipose tissue may also contain regulatory T (Treg) cells, which have the capacity for modulating the immune system. The immunoregulatory and regenerative properties of MSCs make them ideal for use as therapeutic agents in vivo. In this paper we review the literature on the identification, phenotypic characterization and biological properties of MSCs and discuss their potential for applications in cell therapy and regenerative medicine. We also discuss strategies for biomaterial micro-engineering of the stem cell niche.

Mesenchymal stem cells in regenerative medicine: Focus on articular cartilage and intervertebral disc regeneration.

Musculoskeletal disorders represent a major cause of disability and morbidity globally and result in enormous costs for health and social care systems. Development of cell-based therapies is rapidly proliferating in a number of disease areas, including musculoskeletal disorders. Novel biological therapies that can effectively treat joint and spine degeneration are high priorities in regenerative medicine. Mesenchymal stem cells (MSCs) isolated from bone marrow (BM-MSCs), adipose tissue (AD-MSCs) and umbilical cord (UC-MSCs) show considerable promise for use in cartilage and intervertebral disc (IVD) repair. This review article focuses on stem cell-based therapeutics for cartilage and IVD repair in the context of the rising global burden of musculoskeletal disorders. We discuss the biology MSCs and chondroprogenitor cells and specifically focus on umbilical cord/Wharton's jelly derived MSCs and examine their potential for regenerative applications. We also summarize key components of the molecular machinery and signaling pathways responsible for the control of chondrogenesis and explore biomimetic scaffolds and biomaterials for articular cartilage and IVD regeneration. This review explores the exciting opportunities afforded by MSCs and discusses the challenges associated with cartilage and IVD repair and regeneration. There are still many technical challenges associated with isolating, expanding, differentiating, and pre-conditioning MSCs for subsequent implantation into degenerate joints and the spine. However, the prospect of combining biomaterials and cell-based therapies that incorporate chondrocytes, chondroprogenitors and MSCs leads to the optimistic view that interdisciplinary approaches will lead to significant breakthroughs in regenerating musculoskeletal tissues, such as the joint and the spine in the near future.

Bioprinting technologies for disease modeling.

There is a great need for the development of biomimetic human tissue models that allow elucidation of the pathophysiological conditions involved in disease initiation and progression. Conventional two-dimensional (2D) in vitro assays and animal models have been unable to fully recapitulate the critical characteristics of human physiology. Alternatively, three-dimensional (3D) tissue models are often developed in a low-throughput manner and lack crucial native-like architecture. The recent emergence of bioprinting technologies has enabled creating 3D tissue models that address the critical challenges of conventional in vitro assays through the development of custom bioinks and patient derived cells coupled with well-defined arrangements of biomaterials. Here, we provide an overview on the technological aspects of 3D bioprinting technique and discuss how the development of bioprinted tissue models have propelled our understanding of diseases' characteristics (i.e. initiation and progression). The future perspectives on the use of bioprinted 3D tissue models for drug discovery application are also highlighted.

Size controlled ultrafine CeO2 nanoparticles produced by the microwave assisted route and their antimicrobial activity.

Cerium oxide (CeO2) nanoparticles (NPs) have a wide range of biological and biomedical applications. This work describes a new methodology for producing ultrafine, highly uniform NPs with controlled sizes using the chemical microwave assisted route. The size of CeO2-NPs decreased from 10 to 5 nm by increasing the molar ratio of cerium nitrate Ce(NO3)3.(6H2O) to that of hexamethylenetetramine (C6H12N) from 1:20 to 20:20. Detailed information about their structural characterization was obtained from the XRD, UV-visible, photoluminescence, Raman spectroscopy, SEM, TEM and AFM. These CeO2-NPs were tested as antimicrobial agent against Gram-negative (Escherichia.coli), Gram-positive (Bacillus.subtilis) bacteria and yeast (Saccharomyces cerevisiae). The obtained results showed significant inhibition of these strain even at low concentration of CeO2-NPs. The CeO2-NPs with the molar ratio 5:20 had the most effective inhibition against E.coli (~70%) at a concentration of 20 µL. The CeO2-NPs with the ratio 12:20 were found to be the most effective against B.subtilis (inhibition ~68%). On the other hand, CeO2-NPs synthesized with the 20:20 molar ratio caused the highest inhibition for S. cerevisiae (~60%). It is observed that at higher NPs concentration (i.e., >20 µL) the inhibition of these strains decreased. The antimicrobial activity may be attributed to the penetrating power of CeO2-NPs size beside the generated oxygen species radicals that caused inhibition of bacterial growth.

A Highly Elastic and Rapidly Crosslinkable Elastin-Like Polypeptide-Based Hydrogel for Biomedical Applications.

Elastin-like polypeptides (ELPs) are promising for biomedical applications due to their unique thermoresponsive and elastic properties. ELP-based hydrogels have been produced through chemical and enzymatic crosslinking or photocrosslinking of modified ELPs. Herein, a photocrosslinked ELP gel using only canonical amino acids is presented. The inclusion of thiols from a pair of cysteine residues in the ELP sequence allows disulfide bond formation upon exposure to UV light, leading to the formation of a highly elastic hydrogel. The physical properties of the resulting hydrogel such as mechanical properties and swelling behavior can be easily tuned by controlling ELP concentrations. The biocompatibility of the engineered ELP hydrogels is shown in vitro as well as corroborated in vivo with subcutaneous implantation of hydrogels in rats. ELP constructs demonstrate long-term structural stability in vivo, and early and progressive host integration with no immune response, suggesting their potential for supporting wound repair. Ultimately, functionalized ELPs demonstrate the ability to function as an in vivo hemostatic material over bleeding wounds.

Aligned carbon nanotube-based flexible gel substrates for engineering bio-hybrid tissue actuators.

Muscle-based biohybrid actuators have generated significant interest as the future of biorobotics but so far they move without having much control over their actuation behavior. Integration of microelectrodes into the backbone of these systems may enable guidance during their motion and allow precise control over these actuators with specific activation patterns. Here, we addressed this challenge by developing aligned CNT forest microelectrode arrays and incorporated them into scaffolds for stimulating the cells. Aligned CNTs were successfully embedded into flexible and biocompatible hydrogel exhibiting excellent anisotropic electrical conductivity. Bioactuators were then engineered by culturing cardiomyocytes on the CNT microelectrode-integrated hydrogel constructs. The resulting cardiac tissue showed homogeneous cell organization with improved cell-to-cell coupling and maturation, which was directly related to the contractile force of muscle tissue. This centimeter-scale bioactuator has excellent mechanical integrity, embedded microelectrodes and is capable of spontaneous actuation behavior. Furthermore, we demonstrated that a biohybrid machine can be controlled by an external electrical field provided by the integrated CNT microelectrode arrays. In addition, due to the anisotropic electrical conductivity of the electrodes provided from aligned CNTs, significantly different excitation thresholds were observed in different configurations such as the ones in parallel vs. perpendicular direction to the CNT alignment.

A multilayered microfluidic blood vessel-like structure.

There is an immense need for tissue engineered blood vessels. However, current tissue engineering approaches still lack the ability to build native blood vessel-like perfusable structures with multi-layered vascular walls. This paper demonstrated a new method to fabricate tri-layer biomimetic blood vessel-like structures on a microfluidic platform using photocrosslinkable gelatin hydrogel. The presented method enables fabrication of physiological blood vessel-like structures with mono-, bi- or tri-layer vascular walls. The diameter of the vessels, the total thickness of the vessel wall and the thickness of each individual layer of the wall were independently controlled. The developed fabrication process is a simple and rapid method, allowing the physical fabrication of the vascular structure in minutes, and the formation of a vascular endothelial cell layer inside the vessels in 3-5 days. The fabricated vascular constructs can potentially be used in numerous applications including drug screening, development of in vitro models for cardiovascular diseases and/or cancer metastasis, and study of vascular biology and mechanobiology.

Carbon dioxide-activated mesoporous date palm fronds carbon integrated with MnO2/polyaniline for highly efficient capacitive deionization of water.

The continuous population growth and drying up the freshwater reservoirs around the world are increasing the demand for fresh water. Therefore, there is an urgent need to explore newer technologies able to purify water on large scales for human usage. Capacitive deionization is one of the most promising approaches to generate fresh water by the removal of salt ions from brackish water. In this work, we prepared three different capacitive deionization electrodes using carbonized palm tree fronds (PFC). These PFC activation was achieved using CO2 at 900°C. To generate the deionization electrodes, PFC activated carbon was combined with either polyaniline (PANI), MnO2, or both (PFC-PANI, PFC-MnO2, and PFC-MnO2-PANI). The MnO2 and PANI provided additional functionality and enhanced electrical conductivity, which resulted in much higher Na+ and Cl- ions adsorption. The BET surface area of PFC-MnO2-PANI was estimated to be 208.56 m2/g, which is approximately three times that of PCF-PANI and PFC-MnO2 alone. The morphological analysis showed that the PANI and MnO2 nanorods were well dispersed throughout the PFC network. Although PANI and MnO2 is largely embedded inside the PFC network, some remnants are visible on the surface of the electrodes. The cyclic voltammetry (CV) curves showed capacitive behavior of all electrodes in which PFC-MnO2-PANI showed highest specific capacitance of 84 F/g, while the PFC-MnO2 and PFC-PANI showed 42 and 43 F/g, respectively. Owing to its enhanced functionality and CV characteristics, the PFC-MnO2-PANI showed maximum salt adsorption capacity of 10.5 mg/g in contrast to 3.72 and 5.64 mg/g for PFC-MnO2 and PFC-PANI, respectively. Moreover, the measured contact angle for PFC-MnO2-PANI was ~51°, which indicates the hydrophilic nature of electrode that improved ions adsorption. PRACTITIONER POINTS: Date tree fronds were converted into mesopores carbon using CO2 as activation agent. Three composites were prepared with PANI, MnO2, and date palm fronds activated carbon (PFC-MnO2, PFC-MnO2-PANI, and PFC-PANI). Surface area, pore profile, surface morphology, electrochemical behavior, desalination performance, and hydrophilicity of all the electrodes were investigated. The PFC-MnO2-PANI showed maximum salt adsorption capacity of 10.5 mg/g in contrast to 3.72 and 5.64 mg/g for PFC-MnO2 and PFC-PANI, respectively.

Designing Lignin-Based Biomaterials as Carriers of Bioactive Molecules.

There is a need to develop circular and sustainable economies by utilizing sustainable, green, and renewable resources in high-tech industrial fields especially in the pharmaceutical industry. In the last decade, many derivatives of food and agricultural waste have gained considerable attention due to their abundance, renewability, biocompatibility, environmental amiability, and remarkable biological features. Particularly, lignin, which has been used as a low-grade burning fuel in the past, recently attracted a lot of attention for biomedical applications because of its antioxidant, anti-UV, and antimicrobial properties. Moreover, lignin has abundant phenolic, aliphatic hydroxyl groups, and other chemically reactive sites, making it a desirable biomaterial for drug delivery applications. In this review, we provide an overview of designing different forms of lignin-based biomaterials, including hydrogels, cryogels, electrospun scaffolds, and three-dimensional (3D) printed structures and how they have been used for bioactive compound delivery. We highlight various design criteria and parameters that influence the properties of each type of lignin-based biomaterial and corelate them to various drug delivery applications. In addition, we provide a critical analysis, including the advantages and challenges encountered by each biomaterial fabrication strategy. Finally, we highlight the prospects and future directions associated with the application of lignin-based biomaterials in the pharmaceutical field. We expect that this review will cover the most recent and important developments in this field and serve as a steppingstone for the next generation of pharmaceutical research.

Fabrication and Characterization of Oxygen-Generating Polylactic Acid/Calcium Peroxide Composite Filaments for Bone Scaffolds.

The latest advancements in bone scaffold technology have introduced novel biomaterials that have the ability to generate oxygen when implanted, improving cell viability and tissue maturation. In this paper, we present a new oxygen-generating polylactic acid (PLA)/calcium peroxide (CPO) composite filament that can be used in 3D printing scaffolds. The composite material was prepared using a wet solution mixing method, followed by drying and hot melting extrusion. The concentration of calcium peroxide in the composite varied from 0% to 9%. The prepared filaments were characterized in terms of the presence of calcium peroxide, the generated oxygen release, porosity, and antibacterial activities. Data obtained from scanning electron microscopy and X-ray diffraction showed that the calcium peroxide remained stable in the composite. The maximum calcium and oxygen release was observed in filaments with a 6% calcium peroxide content. In addition, bacterial inhibition was achieved in samples with a calcium peroxide content of 6% or higher. These results indicate that an optimized PLA filament with a 6% calcium peroxide content holds great promise for improving bone generation through bone cell oxygenation and resistance to bacterial infections.

Preparation of Polylactic Acid/Calcium Peroxide Composite Filaments for Fused Deposition Modelling.

Fused Deposition Modelling (FDM) 3D printers have gained significant popularity in the pharmaceutical and biomedical industries. In this study, a new biomaterial filament was developed by preparing a polylactic acid (PLA)/calcium peroxide (CPO) composite using wet solution mixing and extrusion. The content of CPO varied from 3% to 24% wt., and hot-melt extruder parameters were optimised to fabricate 3D printable composite filaments. The filaments were characterised using an X-ray diffraction analysis, surface morphology assessment, evaluation of filament extrudability, microstructural analysis, and examination of their rheological and mechanical properties. Our findings indicate that increasing the CPO content resulted in increased viscosity at 200 °C, while the PLA/CPO samples showed microstructural changes from crystalline to amorphous. The mechanical strength and ductility of the composite filaments decreased except for in the 6% CPO filament. Due to its acceptable surface morphology and strength, the PLA/CPO filament with 6% CPO was selected for printability testing. The 3D-printed sample of a bone scaffold exhibited good printing quality, demonstrating the potential of the PLA/CPO filament as an improved biocompatible filament for FDM 3D printing.

Designing Silk-Based Cryogels for Biomedical Applications.

There is a need to develop the next generation of medical products that require biomaterials with improved properties. The versatility of various gels has pushed them to the forefront of biomaterials research. Cryogels, a type of gel scaffold made by controlled crosslinking under subzero or freezing temperatures, have great potential to address many current challenges. Unlike their hydrogel counterparts, which are also able to hold large amounts of biologically relevant fluids such as water, cryogels are often characterized by highly dense and crosslinked polymer walls, macroporous structures, and often improved properties. Recently, one biomaterial that has garnered a lot of interest for cryogel fabrication is silk and its derivatives. In this review, we provide a brief overview of silk-based biomaterials and how cryogelation can be used for novel scaffold design. We discuss how various parameters and fabrication strategies can be used to tune the properties of silk-based biomaterials. Finally, we discuss specific biomedical applications of silk-based biomaterials. Ultimately, we aim to demonstrate how the latest advances in silk-based cryogel scaffolds can be used to address challenges in numerous bioengineering disciplines.

In situ bioprinting: intraoperative implementation of regenerative medicine.

Bioprinting has emerged as a strong tool for devising regenerative therapies to address unmet medical needs. However, the translation of conventional in vitro bioprinting approaches is partially hindered due to challenges associated with the fabrication and implantation of irregularly shaped scaffolds and their limited accessibility for immediate treatment by healthcare providers. An alternative strategy that has recently drawn significant attention is to directly print the bioink into the patient's body, so-called 'in situ bioprinting'. The bioprinting strategy and the associated bioink need to be specifically designed for in situ bioprinting to meet the particular requirements of direct deposition in vivo. In this review, we discuss the developed in situ bioprinting strategies, their advantages, challenges, and possible future improvements.