Immortalized liver cell lines and primary hepatocytes are currently used as in vitro models for hepatotoxic drug screening. However, a decline in the viability and functionality of hepatocytes with time is an important limitation of these culture models. Advancements in tissue engineering techniques have allowed us to overcome this challenge by designing suitable scaffolds for maintaining viable and functional primary hepatocytes for a longer period of time in culture. In the current study, we fabricated liver-specific nanofiber scaffolds with polylactic acid (PLA) along with a decellularized liver extracellular matrix (LEM) by the electrospinning technique. The fabricated hybrid PLA-LEM scaffolds were more hydrophilic and had better swelling properties than the PLA scaffolds. The hybrid scaffolds had a pore size of 38 ± 8 μm and supported primary rat hepatocyte cultures for 10 days. Increased viability (2-fold increase in the number of live cells) and functionality (5-fold increase in albumin secretion) were observed in primary hepatocytes cultured on the PLA-LEM scaffolds as compared to those on conventional collagen-coated plates on day 10 of culture. A significant increase in CYP1A2 enzyme activity was observed in hepatocytes cultured on PLA-LEM hybrid scaffolds in comparison to those on collagen upon induction with phenobarbital. Drugs like acetaminophen and rifampicin showed the highest toxicity in hepatocytes cultured on hybrid scaffolds. Also, the lethal dose of these drugs in rodents was accurately predicted as 1.6 g/kg and 594 mg/kg, respectively, from the corresponding IC50 values obtained from drug-treated hepatocytes on hybrid scaffolds. Thus, the fabricated liver-specific electrospun scaffolds maintained primary hepatocyte viability and functionality for an extended period in culture and served as an effective ex vivo drug screening platform to predict an accurate in vivo drug-induced hepatotoxicity.
Additive Manufacturing is noted for ease of product customization and short production run cost-effectiveness. As our global population approaches 8 billion, additive manufacturing has a future in maintaining and improving average human life expectancy for the same reasons that it has advantaged general manufacturing. In recent years, additive manufacturing has been applied to tissue engineering, regenerative medicine, and drug delivery. Additive Manufacturing combined with tissue engineering and biocompatibility studies offers future opportunities for various complex cardiovascular implants and surgeries. This paper is a comprehensive overview of current technological advancements in additive manufacturing with potential for cardiovascular application. The current limitations and prospects of the technology for cardiovascular applications are explored and evaluated.
Plastics have become an integral part of human life. Single-use plastics (SUPs) are disposable plastics designed to be used once then promptly discarded or recycled. This SUPs range from packaging and takeaway containers to disposable razors and hotel toiletries. Synthetic plastics, which are made of non-renewable petroleum and natural gas resources, require decades to perpetually disintegrate in nature thus contribute to plastic pollution worldwide, especially in marine environments. In response to these problems, bioplastics or bio-based and biodegradable polymers from renewable sources has been considered as an alternative. Understanding the mechanisms behind the degradation of conventional SUPs and biodegradability of their greener counterpart, bioplastics, is crucial for appropriate material selection in the future. This review aims to provide insights into the degradation or disintegration of conventional single-use plastics and the biodegradability of the different types of greener-counterparts, bioplastics, their mechanisms, and conditions. This review highlights on the biodegradation in the environments including composting systems. Here, the various types of alternative biodegradable polymers, such as bacterially biosynthesised bioplastics, natural fibre-reinforced plastics, starch-, cellulose-, lignin-, and soy-based polymers were explored. Review of past literature revealed that although bioplastics are relatively eco-friendly, their natural compositions and properties are inconsistent. Furthermore, the global plastic market for biodegradable plastics remains relatively small and require further research and commercialization efforts, especially considering the urgency of plastic and microplastic pollution as currently critical global issue. Biodegradable plastics have potential to replace conventional plastics as they show biodegradation ability under real environments, and thus intensive research on the various biodegradable plastics is needed to inform stakeholders and policy makers on the appropriate response to the gradually emerging biodegradable plastics.
Exposure of synthetic dye, such as methylene blue (MB), in water bodies led to a serious threat to living things because they are toxic and non-degradable. Amongst the introduced dye removal methods, membrane separation process can be considered a powerful technique for treating dye contamination. However, this method commonly suffered from drawbacks, such as short membrane lifetime, low permeability and selectivity. To overcome these issues, graphene oxide (GO) and titanium dioxide (TiO2) were used as additives to fabricate polyethersulfone (PES)- and polyvinylidene fluoride (PVDF)-based hybrid membranes via non-solvent-induced phase separation method. Prior to membrane fabrication, GO was synthesised via electrochemical exfoliation method assisted by customised triple-tail surfactant. The potential of PES- and PVDF-based hybrid membranes for wastewater treatment has been discussed widely. However, direct comparison between these two polymeric membranes is not critically discussed for MB dye separation application yet. Therefore, this study is aimed at evaluating the performance of different types of polymers (e.g. PES and PVDF) in terms of membrane morphology, properties, dye rejection and antifouling ability. Results showed that the incorporation of GO and TiO2 alters the morphology of the fabricated membranes and affects dye rejection further, as well as their antifouling performance. In contrast with pristine membrane, PES-GO/TiO2 and PVDF-GO/TiO2 possessed high hydrophilicity, as indicated by their low contact angle (67.38° and 62.12°, respectively). Based on this study, PVDF-GO/TiO2 showed higher porosity value (94.88%), permeability (87.32 L/m2hMPa) and MB rejection rate (92.63%), as well as flux recovery ratio value of > 100% as compared with others. Overall, the incorporation of GO and TiO2 with PVDF polymer are proven to be effective hybrid materials of membrane fabrication for dye rejection application in the near future. The polymer material's intrinsic properties can affect the attributes of the fabricated membrane.
Cancer is the leading cause of death, acting as a global burden, severely impacting the patients' quality of life and affecting the world economy despite the expansion of cumulative advances in oncology. The current conventional therapies for cancer which involve long treatment duration and systemic exposure of drugs leads to premature degradation of drugs, a massive amount of pain, side effects, as well as the recurrence of the condition. There is also an urgent demand for personalized and precision-based medicine, especially after the recent pandemic, to avoid future delays in diagnosis or treatments for cancer patients as they are very essential in reducing the global mortality rate. Recently, microneedles which consist of a patch with tiny, micron-sized needles attached to it have been quite a sensation as an emerging technology for transdermal application to diagnose or treat various illnesses. The application of microneedles in cancer therapies is also being extensively studied as they offer a myriad of benefits, especially since microneedle patches offer a better treatment approach through self administration, painless treatment, and being an economically and environmentally friendly approach in comparison with other conventional methods. The painless gains from microneedles significantly improves the survival rate of cancer patients. The emergence of versatile and innovative transdermal drug delivery systems presents a prime breakthrough opportunity for safer and more effective therapies, which could meet the demands of cancer diagnosis and treatment through different application scenarios. This review highlights the types of microneedles, fabrication methods and materials, along with the recent advances and opportunities. In addition, this review also addresses the challenges and limitations of microneedles in cancer therapy with solutions through current studies and future works to facilitate the clinical translation of microneedles in cancer therapies.
Amyloid precursor protein (APP) is a membrane protein expressed in several tissues. The occurrence of APP is predominant in synapses of nerve cells. It acts as a cell surface receptor and plays a vital role as a regulator of synapse formation, iron export and neural plasticity. It is encoded by the APP gene that is regulated by substrate presentation. APP is a precursor protein activated by proteolytic cleavage and thereby generating amyloid beta (Aβ) peptides which eventually form amyloid plaques that accumulate in Alzheimer's disease patients' brains. In this chapter, we highlight basic mechanism, structure, expression patterns and cleavage of amyloid plaques, and its diagnosis and potential treatment for Alzheimer's disease.
Transistor-based sensors have been widely recognized to be highly sensitive and reliable for point-of-care/bed-side diagnosis. In this line, a range of cutting-edge technologies has been generated to elevate the role of transistors for biomolecule detection. Detection of a wide range of clinical biomarkers has been reported using various configurations of transistors. The inordinate sensitivity of transistors to the field-effect imparts high sensitivity toward wide range of biomolecules. This overview has gleaned the present achievements with the technological advancements using high performance transistor-based sensors. This review encloses transistors incorporated with a variety of functional nanomaterials and organic elements for their excellence in selectivity and sensitivity. In addition, the technological advancements in fabrication of these microdevices or nanodevices and functionalization of the sensing elements have also been discussed. The technological gap in the realization of sensors in transistor platforms and the resulted scope for research has been discussed. Finally, foreseen technological advancements and future research perspectives are described.
For a successful delivery of the United Nations Sustainable Development Goals (UNSDGs) and to track the progress of UNSDGs as well as identify the gaps and the areas requiring more attention, periodic analyses on the "research on sustainability" by various countries and their contribution to the topic are inevitable. This paper tracks the trends in sustainability research including the geographical distribution on sustainability research, their level of multi-disciplinarity and the cross-border collaboration, their distribution of funding with respect to the UNSDGs, and the lifecycle analyses. Cumulative publications and patents on sustainability could be fitted to an exponential function, thereby highlighting the importance of the research on sustainability in the recent past. Besides, this analytics quantifies cross-border collaborations and knowledge integration to solve critical issues as well as traditional and emerging sources to undertake sustainability research. As an important aspect of resource sustainability and circular economy, trends in publication and funding on lifecycle assessment have also been investigated. The analytics present here identify that major sustainability research volume is from the social sciences as well as business and economics sectors, whereas contributions from the engineering disciplines to develop technologies for sustainability practices are relatively lower. Similarly, funding distribution is also not evenly distributed under various SDGs; the larger share of funding has been on energy security and climate change research. Thus, this study identifies many gaps to be filled for the UNSDGs to be successful.
A single gene mutation can cause a number of human diseases that affect quality of life. Until the development of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein (Cas) systems, it was challenging to correct a gene mutation to avoid disease by reverting phenotypes. The advent of CRISPR technology has changed the field of gene editing, given its simplicity and intrinsic programmability, surpassing the limitations of both zinc-finger nuclease and transcription activator-like effector nuclease and becoming the method of choice for therapeutic gene editing by overcoming the bottlenecks of conventional gene-editing techniques. Currently, there is no commercially available medicinal cure to correct a gene mutation that corrects and reverses the abnormality of a gene's function. Devising reprogramming strategies for faithful recapitulation of normal phenotypes is a crucial aspect for directing the reprogrammed cells toward clinical trials. The CRISPR-Cas9 system has been promising as a tool for correcting gene mutations in maladies including blood disorders and muscular degeneration as well as neurological, cardiovascular, renal, genetic, stem cell, and optical diseases. In this review, we highlight recent developments and utilization of the CRISPR-Cas9 system in correcting or generating gene mutations to create model organisms to develop deeper insights into diseases, rescue normal gene functionality, and curb the progression of a disease.
Widespread industrialization, rapid urbanization, and massive transport through land, waters, and air have led to catastrophes such as climate change, water pollution, resource limitation, and pandemics causing severe economic consequences, massive influences on the natural environment and pose a great threat to the life sustainability. Sustainability topic has a long history, and many policies and initiatives are in effect for a sustainable planet Earth, still gaps of varying degrees exist in almost all sectors. This article addresses the essentiality of minimising the sustainability gaps exist in diverse realms of life and citing few examples. Creating a cyclic path for production-consumption process in the economic sector through promoting circular economy, learning from the natural processes through appropriate biomimicking, and knowledge-integration from diverse disciplines and emphasizing sustainability in the educational sector are shown to lower the sustainability gaps.
Abstract: Commercially pure titanium and titanium alloys have been among the most commonly used materials for biomedical applications since the 1950s. Due to the excellent mechanical tribological properties, corrosion resistance, biocompatibility, and antibacterial properties of titanium, it is getting much attention as a biomaterial for implants. Furthermore, titanium promotes osseointegration without any additional adhesives by physically bonding with the living bone at the implant site. These properties are crucial for producing high-strength metallic alloys for biomedical applications. Titanium alloys are manufactured into the three types of α, β, and α + β. The scientific and clinical understanding of titanium and its potential applications, especially in the biomedical field, are still in the early stages. This review aims to establish a credible platform for the current and future roles of titanium in biomedicine. We first explore the developmental history of titanium. Then, we review the recent advancement of the utility of titanium in diverse biomedical areas, its functional properties, mechanisms of biocompatibility, host tissue responses, and various relevant antimicrobial strategies. Future research will be directed toward advanced manufacturing technologies, such as powder-based additive manufacturing, electron beam melting and laser melting deposition, as well as analyzing the effects of alloying elements on the biocompatibility, corrosion resistance, and mechanical properties of titanium. Moreover, the role of titania nanotubes in regenerative medicine and nanomedicine applications, such as localized drug delivery system, immunomodulatory agents, antibacterial agents, and hemocompatibility, is investigated, and the paper concludes with the future outlook of titanium alloys as biomaterials.
Polyhydroxyalkanoates (PHA) are biodegradable polymers that are considered able to replace synthetic plastic because their biochemical characteristics are in some cases the same as other biodegradable polymers. However, due to the disadvantages of costly and non-renewable carbon sources, the production of PHA has been lower in the industrial sector against conventional plastics. At the same time, first-generation sugar-based cultivated feedstocks as substrates for PHA production threatens food security and considerably require other resources such as land and energy. Therefore, attempts have been made in pursuit of suitable sustainable and affordable sources of carbon to reduce production costs. Thus, in this review, we highlight utilising waste lignocellulosic feedstocks (LF) as a renewable and inexpensive carbon source to produce PHA. These waste feedstocks, second-generation plant lignocellulosic biomass, such as maize stoves, dedicated energy crops, rice straws, wood chips, are commonly available renewable biomass sources with a steady supply of about 150 billion tonnes per year of global yield. The generation of PHA from lignocellulose is still in its infancy, hence more screening of lignocellulosic materials and improvements in downstream processing and substrate pre-treatment are needed in the future to further advance the biopolymer sector.
Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] is a bacterial derived biopolymer widely known for its unique physical and mechanical properties to be used in biomedical application. In this study, antimicrobial agent silver sulfadiazine (SSD) coat/collagen peptide coat-P(3HB-co-4HB) (SCCC) and SSD blend/collagen peptide coat-P(3HB-co-4HB) scaffolds (SBCC) were fabricated using a green salt leaching technique combined with freeze-drying. This was then followed by the incorporation of collagen peptides at various concentrations (2.5-12.5 wt.%) to P(3HB-co-4HB) using collagen-coating. As a result, two types of P(3HB-co-4HB) scaffolds were fabricated, including SCCC and SBCC scaffolds. The increasing concentrations of collagen peptides from 2.5 wt.% to 12.5 wt.% exhibited a decline in their porosity. The wettability and hydrophilicity increased as the concentration of collagen peptides in the scaffolds increased. In terms of the cytotoxic results, MTS assay demonstrated the L929 fibroblast scaffolds adhered well to the fabricated scaffolds. The 10 wt.% collagen peptides coated SCCC and SBCC scaffolds displayed highest cell proliferation rate. The antimicrobial analysis of the fabricated scaffolds exhibited 100% inhibition towards various pathogenic microorganisms. However, the SCCC scaffold exhibited 100% inhibition between 12 and 24 h, but the SBCC scaffolds with SSD impregnated in the scaffold had controlled release of the antimicrobial agent. Thus, this study will elucidate the surface interface-cell interactions of the SSD-P(3HB-co-4HB)-collagen peptide scaffolds and controlled release of SSD, antimicrobial agent.
Polymethyl methacrylate (PMMA) bone cements (BCs) have some drawbacks, including limited bioactivity and bone formation, as well as inferior mechanical properties, which may result in failure of the BC. To deal with the mentioned issues, novel bioactive polymethyl methacrylate-hardystonite (PMMA-HT) bone cement (BC) reinforced with 0.25 and 0.5 wt% of carbon nanotube (CNT) and reduced graphene oxide (rGO) was synthesized. In this context, the obtained bone cements were evaluated in terms of their mechanical and biological characteristics. The rGO reinforced bone cement exhibited better mechanical properties to the extent that the addition of 0.5 wt% of rGO where its compressive and tensile strength of bioactive PMMA-HT/rGO cement escalated from 92.07 ± 0.72 MPa, and 40.02 ± 0.71 MPa to 187.48 ± 5.79 MPa and 64.92 ± 0.75 MPa, respectively. Besides, the mechanisms of toughening, apatite formation, and cell interaction in CNT and rGO encapsulated PMMA have been studied. Results showed that the existence of CNT and rGO in BCs led to increase of MG63 osteoblast viability, and proliferation. However, rGO reinforced bone cement was more successful in supporting MG63 cell attachment compared to the CNT counterpart due to its wrinkled surface, which made a suitable substrate for cell adhesion. Based on the results, PMMA-HT/rGO can be a proper bone cement for the fixation of load-bearing implants.
Electrospinning is a promising technique for the fabrication of bioscaffolds in tissue engineering applications. Pertaining issues of multiple polymer jets and bending instabilities result in random paths which lend poor controllability over scaffolds morphology for affecting the porosity and mechanical stability. The present study alleviates these challenges by demonstrating a novel self-directing single jet taking a specifically patterned path to deposit fibers into circular and uniform scaffolds without tuning any externally controlled parameters. High-speed camera observation revealed that the charge retention and dissipation on the collected fibers caused rapid autojet switching between the two jetting modes, namely, a microcantilever-like armed jet motion and a whipping motion, which sequentially expand the area and thickness of the scaffolds, respectively, in a layered-like fashion. The physical properties showed that the self-switching dual-jet modes generated multilayered microfibrous scaffolds (MFSs) with dual morphologies and varied fiber packing density, thereby establishing the gradient porosity and mechanical strength (through buckled fibers) in the scaffolds. In vitro studies showed that as-spun scaffolds are cell-permeable hierarchical 3D microporous structures enabling lateral cell seeding into multiple layers. The cell proliferation on days 6 and 9 increased 21% and 38% correspondingly on MFSs than on nanofibrous scaffolds (NFSs) done by conventional multijets electrospinning. Remarkably, this novel and single-step process is highly reproducible and tunable for developing fibrous scaffolds for tissue engineering applications.
Nanobiotechnology has undoubtedly influenced major breakthroughs in medical sciences. Application of nanosized materials has made it possible for researchers to investigate a broad spectrum of treatments for diseases with minimally invasive procedures. Silver nanoparticles (AgNPs) have been a subject of investigation for numerous applications in agriculture, water treatment, biosensors, textiles, and the food industry as well as in the medical field, mainly due to their antimicrobial properties and nanoparticle nature. In general, AgNPs are known for their superior physical, chemical, and biological properties. The properties of AgNPs differ based on their methods of synthesis and to date, the biological method has been preferred because it is rapid, nontoxic, and can produce well-defined size and morphology under optimized conditions. Nevertheless, the common issue concerning biological or biobased production is its sustainability. Researchers have employed various strategies in addressing this shortcoming, such as recently testing agricultural biowastes such as fruit peels for the synthesis of AgNPs. The use of biowastes is definitely cost-effective and eco-friendly; moreover, it has been reported that the reduction process is simple and rapid with reasonably high yield. This review aims to address the developments in using fruit- and vegetable-based biowastes for biologically producing AgNPs to be applied as antimicrobial coatings in biomedical applications.
Global increase in demand for food supply has resulted in surplus generation of wastes. What was once considered wastes, has now become a resource. Studies were carried out on the conversion of biowastes into wealth using methods such as extraction, incineration and microbial intervention. Agro-industry biowastes are promising sources of carbon for microbial fermentation to be transformed into value-added products. In the era of circular economy, the goal is to establish an economic system which aims to eliminate waste and ensure continual use of resources in a close-loop cycle. Biowaste collection is technically and economically practicable, hence it serves as a renewable carbon feedstock. Biowastes are commonly biotransformed into value-added materials such as bioethanol, bioplastics, biofuels, biohydrogen, biobutanol and biogas. This review reveals the recent developments on microbial transformation of biowastes into biotechnologically important products. This approach addresses measures taken globally to valorize waste to achieve low carbon economy. The sustainable use of these renewable resources is a positive approach towards waste management and promoting circular economy.
Recently, increasing public concern about hygiene has been driving many studies to investigate antimicrobial and antiviral agents. However, the use of any antimicrobial agents must be limited due to their possible toxic or harmful effects. In recent years, due to previous antibiotics' lesser side effects, the use of herbal materials instead of synthetic or chemical drugs is increasing. Herbal materials are found in medicines. Herbs can be used in the form of plant extracts or as their active components. Furthermore, most of the world's populations used herbal materials due to their strong antimicrobial properties and primary healthcare benefits. For example, herbs are an excellent material to replace nanosilver as an antibiotic and antiviral agent. The use of nanosilver involves an ROS-mediated mechanism that might lead to oxidative stress-related cancer, cytotoxicity, and heart diseases. Oxidative stress further leads to increased ROS production and also delays the cellular processes involved in wound healing. Therefore, existing antibiotic drugs can be replaced with biomaterials such as herbal medicine with high antimicrobial, antiviral, and antioxidant activity. This review paper highlights the antibacterial, antiviral, and radical scavenger (antioxidant) properties of herbal materials. Antimicrobial activity, radical scavenger ability, the potential for antimicrobial, antiviral, and anticancer agents, and efficacy in eliminating bacteria and viruses and scavenging free radicals in herbal materials are discussed in this review. The presented herbal antimicrobial agents in this review include clove, portulaca, tribulus, eryngium, cinnamon, turmeric, ginger, thyme, pennyroyal, mint, fennel, chamomile, burdock, eucalyptus, primrose, lemon balm, mallow, and garlic, which are all summarized.
In recent years considerable attention has been attracted to magnesium because of its light weight, high specific strength, and ease of recycling. Because of the growing demand for lightweight materials in aerospace, medical and automotive industries, magnesium-based metal matrix nanocomposites (MMNCs) reinforced with ceramic nanometer-sized particles, graphene nanoplatelets (GNPs) or carbon nanotubes (CNTs) were developed. CNTs have excellent material characteristics like low density, high tensile strength, high ratio of surface-to-volume, and high thermal conductivity that makes them attractive to use as reinforcements to fabricate high-performance, and high-strength metal-matrix composites (MMCs). Reinforcing magnesium (Mg) using small amounts of CNTs can improve the mechanical and physical properties in the fabricated lightweight and high-performance nanocomposite. Nevertheless, the incorporation of CNTs into a Mg-based matrix faces some challenges, and a uniform distribution is dependent on the parameters of the fabricating process. The characteristics of a CNTs reinforced composite are related to the uniform distribution, weight percent, and length of the CNTs, as well as the interfacial bonding and alignment between CNTs reinforcement and the Mg-based matrix. In this review article, the recent findings in the fabricating methods, characterization of the composite's properties, and application of Mg-based composites reinforced with CNTs are studied. These include the strategies of fabricating CNT-reinforced Mg-based composites, mechanical responses, and corrosion behaviors. The present review aims to investigate and conclude the most relevant studies conducted in the field of Mg/CNTs composites. Strategies to conquer complicated challenges are suggested and potential fields of Mg/CNTs composites as upcoming structural material regarding functional requirements in aerospace, medical and automotive industries are particularly presented.
X-ray radiation is a harmful carcinogenic electromagnetic source that can adversely affect the health of living species and deteriorate the DNA of cells, thus it's vital to protect vulnerable sources from them. To address this flaw, the conductive polymeric structure of polyaniline (PANi) was reinforced with diverse filler loadings (i.e., 25 wt % and 50 wt %) of hybrid graphene oxide-iron tungsten nitride (ITN) flakes toward attenuation of X-ray beams and inhabitation of microorganisms' growth. Primary characterizations confirmed the successful decoration of graphene oxide (GO) with interconnected and highly dense structure of iron tungsten nitride with a density of about 24.21 g.cm⁻3 and reinforcement of PANi with GO-ITN. Additionally, the outcome of evaluations showed the superior performance of developed shields, where a shield with 1.2 mm thickness containing 50 wt % GO-ITN showed 131.73 % increase in the electrical conductivity (compared with neat PANi) along with 78.07%, 57.12%, and 44.99% decrease in the amplitude of the total irradiated X-ray waves at 30, 40, and 60 kVp tube voltages, respectively, compared with control X-ray dosage. More importantly, the developed shields not only showed non-toxic nature and improved the viability of cells, but also completely removed the selected microorganisms at a concentration of 1000 µg.mL-1.