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Over the past three decades, nanoscience has offered a unique solution for reducing the systemic toxicity of chemotherapy drugs and for increasing drug therapeutic efficiency. However, the poor accumulation and pharmacokinetics of nanoparticles are some of the key reasons for their slow translation into the clinic. The is intimately linked to the non-biological nature of nanoparticles and the aberrant features of solid cancer, which together significantly compromise nanoparticle delivery. New findings on the unique properties of tumors and their interactions with nanoparticles and the human body suggest that, contrary to what was long-believed, tumor features may be more mirage than miracle, as the enhanced permeability and retention based efficacy is estimated to be as low as 1%. In this review, we highlight the current barriers and available solutions to pave the way for approved nanoformulations. Furthermore, we aim to discuss the main solutions to solve inefficient drug delivery with the use of nanobioengineering of nanocarriers and the tumor environment. Finally, we will discuss the suggested strategies to overcome two or more biological barriers with one nanocarrier. The variety of design formats, applications and implications of each of these methods will also be evaluated.

INTRODUCTION: The development of wound dressing materials that combine healing properties, ability to self-repair the material damages, skin-friendly adhesive nature, and competent mechanical properties have surpassing functional importance in healthcare. Due to their specificity, hydrogels have been recognized as a new gateway in biological materials to treat dysfunctional tissues. The design and creation of injectable hydrogel-based scaffolds have extensively progressed in recent years to improve their therapeutic efficacy and to pave the way for their easy minimally invasive administration. Hence, injectable hydrogel biomaterials have been prepared to eventually translate into minimally invasive therapy and pose a lasting effect on regenerative medicine.AREAS COVERED: This review highlights the recent development of adhesive and injectable hydrogels that have applications in wound healing and wound dressing. Such hydrogel materials are not only expected to improve therapeutic outcomes but also to facilitate the easy surgical process in both wound healing and dressing.EXPERT OPINION: Wound healing seems to be an appealing approach for treating countless life-threatening disorders. With the average increase of life expectancy in human societies, an increase in demand for injectable skin replacements and drug delivery carriers for chronic wound healing is expected.

Periodontitis is a ubiquitous chronic inflammatory, bacteria-triggered oral disease affecting the adult population. If left untreated, periodontitis can lead to severe tissue destruction, eventually resulting in tooth loss. Despite previous efforts in clinically managing the disease, therapeutic strategies are still lacking. Herein, melt electrowriting (MEW) is utilized to develop a compositionally and structurally tailored graded scaffold for regeneration of the periodontal ligament-to-bone interface. The composite scaffolds, consisting of fibers of polycaprolactone (PCL) and fibers of PCL-containing magnesium phosphate (MgP) were fabricated using MEW. To maximize the bond between bone (MgP) and ligament (PCL) regions, we evaluated two different fiber architectures in the interface area. These were a crosshatch pattern at a 0/90° angle and a random pattern. MgP fibrous scaffolds were able to promote in vitro bone formation even in culture media devoid of osteogenic supplements. Mechanical properties after MgP incorporation resulted in an increase of the elastic modulus and yield stress of the scaffolds, and fiber orientation in the interfacial zone affected the interfacial toughness. Composite graded MEW scaffolds enhanced bone fill when they were implanted in an in vivo periodontal fenestration defect model in rats. The presence of an interfacial zone allows coordinated regeneration of multitissues, as indicated by higher expression of bone, ligament, and cementoblastic markers compared to empty defects. Collectively, MEW-fabricated scaffolds having compositionally and structurally tailored zones exhibit a good mimicry of the periodontal complex, with excellent regenerative capacity and great potential as a defect-specific treatment strategy.

Myocardial infarction (MI) is still the leading cause of mortality worldwide. The success of cell-based therapies and tissue engineering strategies for treatment of injured myocardium have been notably hindered due to the limitations associated with the selection of a proper cell source, lack of engraftment of engineered tissues and biomaterials with the host myocardium, limited vascularity, as well as immaturity of the injected cells. The first-generation approaches in cardiac tissue engineering (cTE) have mainly relied on the use of desired cells (e.g., stem cells) along with non-conductive natural or synthetic biomaterials for in vitro construction and maturation of functional cardiac tissues, followed by testing the efficacy of the engineered tissues in vivo. However, to better recapitulate the native characteristics and conductivity of the cardiac muscle, recent approaches have utilized electroconductive biomaterials or nanomaterial components within engineered cardiac tissues. This review article will cover the recent advancements in the use of electrically conductive biomaterials in cTE. The specific emphasis will be placed on the use of different types of nanomaterials such as gold nanoparticles (GNPs), silicon-derived nanomaterials, carbon-based nanomaterials (CBNs), as well as electroconductive polymers (ECPs) for engineering of functional and electrically conductive cardiac tissues. We will also cover the recent progress in the use of engineered electroconductive tissues for in vivo cardiac regeneration applications. We will discuss the opportunities and challenges of each approach and provide our perspectives on potential avenues for enhanced cTE. STATEMENT OF SIGNIFICANCE: Myocardial infarction (MI) is still the primary cause of death worldwide. Over the past decade, electroconductive biomaterials have increasingly been applied in the field of cardiac tissue engineering. This review article provides the readers with the leading advances in the in vitro applications of electroconductive biomaterials for cTE along with an in-depth discussion of injectable/transplantable electroconductive biomaterials and their delivery methods for in vivo MI treatment. The article also discusses the knowledge gaps in the field and offers possible novel avenues for improved cardiac tissue engineering.

Cellular therapies are poised to transform the field of medicine by restoring dysfunctional tissues and treating various diseases in a dynamic manner not achievable by conventional pharmaceutics. Spanning various therapeutic areas inclusive of cancer, regenerative medicine, and immune disorders, cellular therapies comprise stem or non-stem cells derived from various sources. Despite numerous clinical approvals or trials underway, the host immune response presents a critical impediment to the widespread adoption and success of cellular therapies. Here, we review current research and clinical advances in immunomodulatory strategies to mitigate immune rejection or promote immune tolerance to cellular therapies. We discuss the potential of these immunomodulatory interventions to accelerate translation or maximize the prospects of improving therapeutic outcomes of cellular therapies for clinical success.

Conventional drug delivery systems are challenged by concerns related to systemic toxicity, repetitive doses, drug concentrations fluctuation, and adverse effects. Various drug delivery systems are developed to overcome these limitations. Nanomaterials are employed in a variety of biomedical applications such as therapeutics delivery, cancer therapy, and tissue engineering. Physiochemical nanoparticle assembly techniques involve the application of solvents and potentially harmful chemicals, commonly at high temperatures. Genetically engineered organisms have the potential to be used as promising candidates for greener, efficient, and more adaptable platforms for the synthesis and assembly of nanomaterials. Genetically engineered carriers are precisely designed and constructed in shape and size, enabling precise control over drug attachment sites. The high accuracy of these novel advanced materials, biocompatibility, and stimuli-responsiveness, elucidate their emerging application in controlled drug delivery. The current article represents the research progress in developing various genetically engineered carriers. Organic-based nanoparticles including cellulose, collagen, silk-like polymers, elastin-like protein, silk-elastin-like protein, and inorganic-based nanoparticles are discussed in detail. Afterward, viral-based carriers are classified, and their potential for targeted therapeutics delivery is highlighted. Finally, the challenges and prospects of these delivery systems are concluded.

In this study, a novel nanofibrous hybrid scaffold based on silk fibroin (SF) and different weight ratios of

Today's consumer electronics are made from nonrenewable and toxic components. They are also rigid, bulky, and manufactured in an energy-inefficient manner via CO2-generating routes. Though petroleum-based polymers such as polyethylene terephthalate and polyethylene naphthalate can address the rigidity issue, they have a large carbon footprint and generate harmful waste. Scalable routes for manufacturing electronics that are both flexible and ecofriendly (Fleco) could address the challenges in the field. Ideally, such substrates must incorporate into electronics without compromising device performance. In this work, we demonstrate that a new type of wood-based [nanocellulose (NC)] material made via nanosilicate (NS) reinforcement can yield flexible electronics that can bend and roll without loss of electrical function. Specifically, the NSs interact electrostatically with NC to reinforce thermal and mechanical properties. For instance, films containing 34 wt % of NS displayed an increased young's modulus (1.5 times), thermal stability (290 → 310 °C), and a low coefficient of thermal expansion (40 ppm/K). These films can also easily be separated and renewed into new devices through simple and low-energy processes. Moreover, we used very cheap and environmentally friendly NC from American Value Added Pulping (AVAP) technology, American Process, and therefore, the manufacturing cost of our NS-reinforced NC paper is much cheaper ($0.016 per dm-2) than that of conventional NC-based substrates. Looking forward, the methodology highlighted herein is highly attractive as it can unlock the secrets of Fleco electronics and transform otherwise bulky, rigid, and "difficult-to-process" rigid circuits into more aesthetic and flexible ones while simultaneously bringing relief to an already-overburdened ecosystem.

Bone tissue engineering has come on the scene to overcome the difficulties of the current treatment strategies. By combining biomaterials, active agents and growth factors, cells and nanomaterials, tissue engineering makes it possible to create new structures that enhance bone regeneration. Herein, hyaluronic acid and alginate were used to create biologically active hydrogels, and montmorillonite nanoclay was used to reinforce and stabilize them. The developed scaffolds were found to be biocompatible and osteogenic with mMSCs in vitro, especially those reinforced with the nanoclay, and allowed mineralization even in the absence of differentiation media. Moreover, an in vivo investigation was performed to establish the potential of the hydrogels to mend bone and act as cell-carriers and delivery platforms for SDF-1. Scaffolds embedded with SDF-1 exhibited the highest percentages of bone regeneration as well as of angiogenesis, which confirms the suitability of the scaffolds for bone. Although there are a number of obstacles to triumph over, these bioengineered structures showed potential as future bone regeneration treatments. This work was supported by the Spanish Ministry of Economy, Industry, and Competitiveness (PID2019-106094RB-I00/AEI/10.13039/501100011033) and technical assistance from the ICTS NANBIOSIS (Drug Formulation Unit, U10) at the University of the Basque Country. We also appreciate the support from the Basque Country Government (Grupos Consolidados, No ref: IT907-16) . I. Erezuma and I. Lukin thank to the Basque Government for the PhD grants (PRE_2021_2_0021 & PRE_2021_2_0023) . C. Pimenta-Lopes is a recipient of a F.P.U. fellowship from the Ministry of Universidades. A.D.-P. would like to acknowledge the Danish Council for Independent Research (Technology and Production Sciences, 8105-00003B) , and the VIDI research programme with project number R0004387, which is (partly) financed by The Netherlands Organisation for Scientific Research (NWO) . This work has also received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 951747.

In vitro small intestinal models aim to mimic the in vivo intestinal function and structure, including the villi architecture of the native tissue. Accurate models in a scalable format are in great demand to advance, for example, the development of orally administered pharmaceutical products. Widely used planar intestinal cell monolayers for compound screening applications fail to recapitulate the three-dimensional (3D) microstructural characteristics of the intestinal villi arrays. This study employs stereolithographic 3D printing to manufacture biocompatible hydrogel-based scaffolds with villi-like micropillar arrays of tunable dimensions in poly(ethylene glycol) diacrylates (PEGDAs). The resulting 3D-printed microstructures are demonstrated to support a month-long culture and induce apicobasal polarization of Caco-2 epithelial cell layers along the villus axis, similar to the native intestinal microenvironment. Transport analysis requires confinement of compound transport to the epithelial cell layer within a compound diffusion-closed reservoir compartment. We meet this challenge by sequential printing of PEGDAs of different molecular weights into a monolithic device, where a diffusion-open villus-structured hydrogel bottom supports the cell culture and mass transport within the confines of a diffusion-closed solid wall. As a functional demonstrator of this scalable dual-material 3D micromanufacturing technology, we show that Caco-2 cells seeded in villi-wells form a tight epithelial barrier covering the villi-like micropillars and that compound-induced challenges to the barrier integrity can be monitored by standard high-throughput analysis tools (fluorescent tracer diffusion and transepithelial electrical resistance).

Osteoarthritis of the hip is a painful and debilitating condition commonly occurring in humans and dogs. One of the main causes that leads to hip osteoarthritis is hip dysplasia. Although the current surgical methods to correct dysplasia work satisfactorily in many circumstances, these are associated with serious complications, tissue resorption, and degeneration. In this study, a one-step fabrication of a regenerative hip implant with a patient-specific design and load-bearing properties is reported. The regenerative hip implant is fabricated based on patient imaging files and by an extrusion assisted 3D printing process using a flexible, bone-inducing biomaterial. The novel implant can be fixed with metallic screws to host bone and can be loaded up to physiological loads without signs of critical permanent deformation or failure. Moreover, after exposing the hip implant to accelerated in vitro degradation, it is confirmed that it is still able to support physiological loads even after losing ≈40% of its initial mass. In addition, the osteopromotive properties of the novel hip implant is demonstrated as shown by an increased expression of osteonectin and osteocalcin by cultured human mesenchymal stem cells after 21 days. Overall, the proposed hip implant provides an innovative regenerative and mechanically stable solution for hip dysplasia treatment.

Biomaterials capable of transmitting signals over longer distances than those in rigid electronics can open new opportunities for humanity by mimicking the way tissues propagate information. For seamless mirroring of the human body, they also have to display conformability to its curvilinear architecture, as well as, reproducing native-like mechanical and electrical properties combined with the ability to self-heal on demand like native organs and tissues. Along these lines, a multifunctional composite is developed by mixing silk fibroin and reduced graphene oxide. The material is coined "CareGum" and capitalizes on a phenolic glue to facilitate sacrificial and hierarchical hydrogen bonds. The hierarchal bonding scheme gives rise to high mechanical toughness, record-breaking elongation capacity of approximate to 25 000%, excellent conformability to arbitrary and complex surfaces, 3D printability, a tenfold increase in electrical conductivity, and a fourfold increase in Young's modulus compared to its pristine counterpart. By taking advantage of these unique properties, a durable and self-healing bionic glove is developed for hand gesture sensing and sign translation. Indeed, CareGum is a new advanced material with promising applications in fields like cyborganics, bionics, soft robotics, human-machine interfaces, 3D-printed electronics, and flexible bioelectronics.

Item does not contain fulltext Nanoclay-reinforced biomaterials have sparked a new avenue in advanced healthcare materials that can potentially revolutionize treatment of musculoskeletal defects. Native tissues display many important chemical, mechanical, biological, and physical properties that engineered biomaterials need to mimic for optimal tissue integration and regeneration. However, it is time-consuming and difficult to endow such combinatorial properties on materials via feasible and nontoxic procedures. Fortunately, a number of nanomaterials such as graphene, carbon nanotubes, MXenes, and nanoclays already display a plethora of material properties that can be transferred to biomaterials through a simple incorporation procedure. In this direction, the members of the nanoclay family are easy to functionalize chemically, they can significantly reinforce the mechanical performance of biomaterials, and can provide bioactive properties by ionic dissolution products to upregulate cartilage and bone tissue formation. For this reason, nanoclays can become a key component for future orthopedic biomaterials. In this review, we specifically focus on the rapidly decreasing gap between clinic and laboratory by highlighting their application in a number of promising in vivo studies.

Soft and electrically active materials are currently being utilized for intelligent systems, including electronic skin, cybernetics, soft robotics, and wearable devices. However, fabricating materials that fulfill the complex requirements of such advanced applications remains a challenge. These attributes include electronic, adhesive, self-healing, flexible, moldable, printable, and strong mechanical properties. Inspired by the recent interest in transforming monofunctional materials into multifunctional ones through nanoreinforcement and mussel-inspired chemistry, we have designed a simple two-step methodology based on halloysite nanotube (HNT) and polydopamine (PDA) to address the grand challenges in the field. In brief, HNTs were coated with PDA and embedded within a poly(vinyl alcohol) (PVA)-based polymeric matrix in combination with ferric ions (Fe

The development of nanoparticles (NPs) with potential therapeutic uses represents an area of vast interest in the scientific community during the last years. Recently, the pandemic caused by COVID-19 motivated a race for vaccines creation to overcome the crisis generated. This is a good demonstration that nanotechnology will most likely be the basis of future immunotherapy. Moreover, the number of publications based on nanosystems has significantly increased in recent years and it is expected that most of these developments can go on to experimentation in clinical stages soon. The therapeutic use of NPs to combat different diseases such as cancer, allergies or autoimmune diseases will depend on their characteristics, their targets, and the transported molecules. This review presents an in-depth analysis of recent advances that have been developed in order to obtain novel nanoparticulate based tools for the treatment of allergies, autoimmune diseases and for their use in vaccines. Moreover, it is highlighted that by providing targeted delivery an increase in the potential of vaccines to induce an immune response is expected in the future. Definitively, the here gathered analysis is a good demonstration that nanotechnology will be the basis of future immunotherapy.

This study demonstrates a two-step approach that enables quantification of concrete printability through dynamics mode rheological measurements; I) modeling shearing history during extrusion; II) monitoring the hardening evolution of deposited material by applying a strain smaller than the critical strain. It is shown that the shearing history of the material is removed by imposing a pre-shearing above the critical strain, and zero value yield stress is measured for all specimens. At step II, a linear extrapolation of the green strength development can quantify the static yield stress at the origin, which we used to quantify the material printability. As far as this yield stress surpasses the stress level that exists in the printed structure, the material retains its shape stability. We show the performance of the model on a series of geopolymer mortars with a wide range of rheological properties as a function of material composition, aging, and pre-shearing consequences.

Contains fulltext : 232768.pdf (Publisher’s version ) (Open Access) Cell therapy has the potential to regenerate cardiac tissue and treat a variety of cardiac diseases which are currently without effective treatment. This novel approach to treatment has demonstrated clinical efficiency, despite low retention of the cell products in the heart. It has been shown that improving retention often leads to improved functional outcome. A feasible method of improving cell graft retention is administration of injectable hydrogels. Over the last decade, a variety of injectable hydrogels have been investigated preclinically for their potential to improve the effects of cardiac cell therapy. These hydrogels are created with different polymers, properties, and additional functional motifs and differ in their approaches for encapsulating different cell types. Only one combinational therapy has been tested in a clinical randomized controlled trial. In this review, the latest research on the potential of injectable hydrogels for delivery of cell therapy is discussed, together with potential roadblocks for clinical translation and recommendations for future explorations to facilitate future translation.

Contains fulltext : 238926.pdf (Publisher’s version ) (Closed access) Soft and electrically active materials are currently being utilized for intelligent systems, including electronic skin, cybernetics, soft robotics, and wearable devices. However, fabricating materials that fulfill the complex requirements of such advanced applications remains a challenge. These attributes include electronic, adhesive, self-healing, flexible, moldable, printable, and strong mechanical properties. Inspired by the recent interest in transforming monofunctional materials into multifunctional ones through nanoreinforcement and mussel-inspired chemistry, we have designed a simple two-step methodology based on halloysite nanotube (HNT) and polydopamine (PDA) to address the grand challenges in the field. In brief, HNTs were coated with PDA and embedded within a poly(vinyl alcohol) (PVA)-based polymeric matrix in combination with ferric ions (Fe(3+)). The final composite displayed a 3-fold increase in electrical conductivity, a 20-fold increase in mechanical stiffness, and a 7-fold increase in energy dissipation in comparison to their nonfunctional counterparts, which arose from a combination of nanotube alignment and mussel-inspired chemistry. Moreover, the developed composite could elongate up to 30000% of its original length, maintain its electrical properties after 600% strain, self-heal within seconds (both electrically and mechanically), and display strain-sensitivity. Finally, it was 3D-printable and thus amenable for engineering of customized wearable electronics.

There are currently several commercialized products approved by the Food and Drug Administration and the European Medicines Agency based on the use of recombinant human BMP-2 for the treatment of non-unions long fractures and spinal fusion. However, the adverse effects recorded with the use of BMPs suggest the need for drug delivery carriers that allow reducing the required doses and improve their cost-effectiveness. Herein, we have developed a new osteoconductive scaffold that reduces the required doses of BMP-2 for promoting bone regeneration in an osteoporotic defect model. The composite is, in brief, a gelatin-based 3D scaffold reinforced with either calcium sulfate or hydroxyapatite as an inorganic osteoconductive biomaterial. To this end, the organic/inorganic composite systems showed high hydration capacity and good in vitro degradability. The incorporation of 7.5% (m/v) ceramic compounds resulted in scaffolds with stiffer Young modulus (179 and 75 kPa for CaSO4_7 and HA_7, respectively) than bare gelatin hydrogels (48 kPa). Studies with human bone-marrow derived mesenchymal stem cells (hBM-MSCs) revealed that the 3D scaffolds promote cell adhesion and proliferation along with osteogenic differentiation capabilities. Specifically, downregulation of stemness (Nanog, Oct4) genes and upregulation of osteogenic markers (ALP, Col1a1, Fmod) by two fold were observed over 10 days under basal culture conditions. Promisingly, the sustained in vitro release of BMP-2 observed from the porous reinforced scaffolds allowed us to address the critical-sized osteoporotic mice calvarial defects with a relatively low growth factor doses (600 ng BMP-2/scaffold) compared to conventional doses at 2–15 micrograms. Overall, this study demonstrates the promising potential of osteoconductive gelatin/calcium bioceramics composites as osteogenic growth factors delivery carriers for bone-regeneration via ultra-low growth factor doses.

[EN]The development of aggregation-induced emission (AIE) has received extreme considerations from basic and clinical researches. To date, various luminogens with AIE property (AIEgens) have been broadly utilized in optoelectronic devices, fluorescent bio-probes, drug delivery, anticancer and chemosensors and many more. Scientists have likewise dedicated to investigating the possibilities of AIEgens in the biomedical field. Among the various AIE luminophores studied, tetraphenylethylene (TPE) derivatives have demonstrated as most promising AIEgen, owing to their capacity in self-organization and conjugation with aggregation-caused quenching (ACQ) fluorophores to form larger multi-component assemblies. It likewise generally utilized in different fields, like organic and therapeutic science, supramolecular chemistry, organic electronics, cancer therapy, apoptosis and inflammation, microorganism imaging therapy etc. This review encompasses the recent advances of TPE based AIE-active luminophores and their potential applications in biomolecular science. K.S. Rangappa acknowledge CSIR for providing an emeritus scientist fellowship. GO wish to thank the Spanish Ministry of Economy, Industry, and Competitiveness (SAF2016-76150-R and BFU2017-82421-P) and technical assistance from the ICTS NANBIOSIS (Drug Formulation Unit, U10) at the University of the Basque Country.

Fluorination of graphene nanomaterials has multitude merits owing to the peculiar temperament of the carbon-fluorine (C-F) bond. However, the current synthesis modalities of fluorinated graphene (FG) are based on the usage of toxic materials at high temperatures, which are problematic to be used. The methods to overcome these problems are challenging for chemists. Ionic liquids (ILs) have been used in several chemical processes as auxiliaries and eco-friendly alternatives instead of volatile organic solvents because of their properties. Consequently, herein we exploited a highly effective and green process for the synthesis of FG at mild temperature (80 °C) by using ammonium fluoride salt as fluorine agent and a synthesized acidic IL ([TEA]+[TFA]–) as a solvent. Our goal was to synthesize enriched FG with a high degree of fluorination (66.4 wt.% of F) and F/C ratio (2.2), which measured and confirmed by XPS analysis. Subsequently, the obtained FG was used as a nanocarrier for delivery of curcumin to cancerous cells. The in-vitro results showed that these nanosheets possessed a higher Cur-loading efficiency (78.43%) than commercial FG (52.12%) due to the sheet-like structure with folded edges. This, in turn, translated into an excellent in-vitro anti-cancer effect when tested against cancerous cells.

Endothelial cell migration is a crucial step in the process of new blood vessel formation - a necessary process to maintain cell viability inside thick tissue constructs. Here, we report a new method for maintaining cell viability and inducing cell migration using a perfused microfluidic platform based on collagen gel and a gradient hydrogel sheet. Due to the helpful role of the extracellular matrix components in cell viability, we developed a hydrogel sheet from decellularized tissue (DT) of the bovine heart and chitosan (CS). The results showed that hydrogel sheets with an optimum weight ratio of CS/DT = 2 possess a porosity of around 75%, a mechanical strength of 23 kPa, and display cell viability up to 78%. Then, we immobilized a radial gradient of vascular endothelial growth factor (VEGF) on the hydrogel sheet to promote human umbilical vein endothelial cell migration. Finally, we incorporated the whole system as an entirety on the top of the microfluidic platform and studied cell migration through the hydrogel sheet in the presence of soluble and immobilized VEGF. The results demonstrated that immobilized VEGF stimulated cell migration in the hydrogel sheet at all depths compared with soluble VEGF. The results also showed that applying a VEGF gradient in both soluble and immobilized states had a significant effect on cell migration at limited depths (

With the ever-increasing prevalence of life-threatening diseases such as cancer, cardiovascular diseases, and neurological disorders, there is an unmet need to develop new therapies with significantly better clinical outcomes. However, the drug development process has failed to develop new drugs because it relies on conventional two-dimensional in vitro assays and animal models that are unable to fully recapitulate the critical characteristics of the human pathophysiology. The recent emergence of advanced manufacturing techniques and micro- and nanotechnologies has sparked an array of opportunities for the pharmaceutical companies to evaluate new drugs in more biomimetic tissue models. Further, these models have enabled researchers to investigate the molecular and cellular mechanisms underlying disease formation and progression, which in return can lead to the development of new treatment strategies. Here, we discuss the current state-of-the-art in bioengineered organ and tissue models with special emphasis on advanced manufacturing techniques and rational design of biomaterials. Lastly, we will summarize recent studies on bioengineered organs for disease modeling.

Item does not contain fulltext Imagine a world where machines can program cells to deliver therapeutics in a remote-controlled, time-specific, and targeted manner. Or, what if physicians could collect data continuously to establish intimate links between therapy and disease progression? Such machine biology systems could empower physicians beyond imagination and give rise to personalized treatments.

Contains fulltext : 218172.pdf (Publisher’s version ) (Closed access) Hydrogel structures with microscale morphological features have extensive application in tissue engineering owing to their capacity to induce desired cellular behavior. Herein, we describe a novel biofabrication method for fabrication of grooved solid and hollow hydrogel fibers with control over their cross-sectional shape, surface morphology, porosity, and material composition. These fibers were further configured into three-dimensional structures using textile technologies such as weaving, braiding, and embroidering methods. Additionally, the capacity of these fibers to integrate various biochemical and biophysical cues was shown via incorporating drug-loaded microspheres, conductive materials, and magnetic particles, extending their application to smart drug delivery, wearable or implantable medical devices, and soft robotics. The efficacy of the grooved fibers to induce cellular alignment was evaluated on various cell types including myoblasts, cardiomyocytes, cardiac fibroblasts, and glioma cells. In particular, these fibers were shown to induce controlled myogenic differentiation and morphological changes, depending on their groove size, in C2C12 myoblasts.

Contains fulltext : 225369.pdf (Publisher’s version ) (Closed access) INTRODUCTION: Diabetes mellitus is an ever-increasing medical condition that currently suffers 1 of 11 adults who may have lifelong commitment with insulin injections. Cell-laden hydrogels releasing insulin may provide the ultimate means of correcting diabetes. Here, we provide insights of this cell-based approach including latest preclinical and clinical progress both from academia and industry. AREA COVERED: The present article focuses on reviewing latest advances in cell-laden hydrogels both from the technological and biological perspective. The most relevant clinical results including clinical trials are also discussed. EXPERT OPINION: Current progress in technological issues (stem cells, devices, biomaterials) have contributed cell encapsulation science to have a very relevant progress in the field of diabetes treatment.

One of the long-standing challenges in materials science involves synthesizing biomaterials that recapitulate important features of native biological tissues. Even though, the number of available biomaterials at the moment are virtually limitless, few of them has unlocked all the secrets of the human body by mimicking the combinatorial-like material properties of our tissues and organs. Inspired by the human body, we have developed a polymeric gum, which combines stretchability, toughness, strength, flexibility, and self-healing. It also exhibits a high bioactivity that can target and eliminate bacterial infections fast and reliably. Notably, this material is moldable into almost any complex shape, and therefore suitable as a building block for wearables designed to conform directly with the curved and personalized anatomy of patients. It also exhibits excellent drug retention and release capacity, which altogether makes it suitable for applications in personalized wearable drug-delivery devices.

Nanotechnology based drug delivery systems have been explored extensively in cancer therapy over the past decades. Among the vast number of different materials used in nanocarrier systems, natural biopolymers are most frequently used in the encapsulation of chemotherapeutic drugs. However, the low solubility of these agents within biological fluid has decreased their efficacy for inhibiting the growth of cancer cells. Herein, we have developed a new biodegradable and biocompatible drug delivery system based on Dextran. Specifically, we have prepared lipid-conjugated dextran through esterification process using stearic acid (SA) and cholesterol (Chol). In vitro toxicity studies of unloaded and rapamycin loaded nanocarriers with U87 MG cell line showed that unloaded nanocarriers were non-toxic, and the IC50 value of encapsulated rapamycin for different formulations was lower than that for free rapamycin after 24 and 48 h incubation. Also, flow cytometry analysis fully supported the time dependent uptake of the nanocarriers by the cells. These results show that the synthesized polymers can potentially be used as a self-assembled carrier for loading of hydrophobic chemotherapeutics with enhanced toxicity against tumoral cancer cells.

Over the past decades, natural polysaccharides have received considerable attention to developing nano-drug delivery systems for the delivery of anticancer drugs. However, the low solubility of these agents within the biological fluid has reduced their efficacy in inhibiting the growth of cancer cells. In this study, self-assembled cationic polysaccharides based on dextran-stearic acid-spermine conjugates (D-SASp) were synthesized, and their potential as carriers for sustained release of rapamycin was demonstrated. Nanomicelles (smaller than 200 nm) with relatively narrow size distribution were obtained through dialysis of D-SASp solution in DMSO against distilled water. The sustained release of rapamycin from nanocarriers occurred without initial burst release. The in vitro toxicity studies with the U87 MG cell line confirmed that synthesized polymers were not toxic up to 0.4 mg/mL, and cytotoxicity of rapamycin-loaded micelles was higher than that of free rapamycin. Furthermore, flow cytometry analysis fully supported the time-dependent cellular uptake of the nanocarriers. In addition, the presence of conjugated spermine with a positive charge resulted in increased transport of the nanomicelles into the cells.

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.

The effect of a permanent magnetic field on the heat transfer characteristics of hybrid graphene-magnetite nanofluids (hybrid nanofluid) under forced laminar flow was experimentally investigated. For this purpose, a reduced graphene oxide-Fe3O4 was synthesized by using two-dimensional (2D) graphene oxide, iron salts and tannic acid as the reductant and stabilizer. Graphene sheets acted as the supporting materials to enhance the stability and thermal properties of magnetite nanoparticles. The thermo-physical and magnetic properties of this hybrid nanofluid have been widely characterized and it shows that the thermal conductivity increased up to 11%. The hybrid nanofluid behaves as a Newtonian fluid with liquid like behavior with superparamagnetic properties as was evident from its magnetic saturation value at 45.9 emu/g. Moreover, the experimental heat-transfer results indicated that the heat transfer enhancement of the hybrid nanofluid compared to the control fluid (distilled water) was negligible when no magnetic field was applied. Additionally, the convective heat transfer was significantly improved under the influence of a magnetic field with a maximum enhancement of 82% in terms of the convective heat transfer properties of the hybrid nanofluid.