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Irregular hemodynamics affects the progression of various vascular diseases, such atherosclerosis or aneurysms. Despite the extensive hemodynamics studies on animal models, the inter-species differences between humans and animals hamper the translation of such findings. Recent advances in vascular tissue engineering and the suitability of in vitro models for interim analysis have increased the use of in vitro human vascular tissue models. Although the effect of flow on endothelial cell (EC) pathophysiology and EC-flow interactions have been vastly studied in two-dimensional systems, they cannot be used to understand the effect of other micro- and macro-environmental parameters associated with vessel wall diseases. To generate an ideal in vitro model of the vascular system, essential criteria should be included: 1) the presence of smooth muscle cells or perivascular cells underneath an EC monolayer, 2) an elastic mechanical response of tissue to pulsatile flow pressure, 3) flow conditions that accurately mimic the hemodynamics of diseases, and 4) geometrical features required for pathophysiological flow. In this paper, we review currently available in vitro models that include flow dynamics and discuss studies that have tried to address the criteria mentioned above. Finally, we critically review in vitro fluidic models of atherosclerosis, aneurysm, and thrombosis.

Hydrogels are important biomaterials that have several applications in drug and cell delivery, tissue engineering, three-dimensional (3D) printing and more recently, in sensing and actuating applications. With the advent of self-healing hydrogels, it is becoming possible to have smarter materials with sustainable mechanical properties under stress and also added functionalities. The mechanisms responsible for the self-healing behavior of these materials are related to their internal structure and processes triggered by damage they may sustain. These mechanisms rely on either chemical bonding or physical interactions of the structural components of hydrogels, or on both. Many self-healing hydrogels have been developed and tested in vitro and in animals. However, there are still challenges, especially with healing characteristics that need to be addressed and investigated in animal experiments before their clinical applications can be initiated, for which a multidisciplinary approach is required. In the current paper, various biomedical applications of self-healing hydrogels are discussed in detail, highlighting current challenges and future prospects.

The efficiency of injectable biomaterials as minimally invasive therapeutics significantly relies on biomaterial's characteristics, such as stability, biodegradation rate, and interaction with the host tissue, which requires real‐time tracking of the biomaterials. Fluorescence imaging is considered as a noninvasive technique for monitoring biomaterials; however, the commonly used fluorescent agents are often accompanied by photobleaching and toxicity. Herein, graphene quantum dots (GQDs) are introduced as a biocompatible and stable fluorophore for imaging and noninvasive monitoring of a physically cross‐linked injectable shear‐thinning biomaterial (STB) of gelatin–silicate nanoplatelets. Silicate nanoplatelets and GQDs serve as the physical cross‐linkers of gelatin making electrostatic interaction with gelatin chains. Different STB‐GQDs formulations are assessed in terms of fluorescence intensity, injectability, thermal stability, and cellular biocompatibility. STB‐GQDs with 0.06% GQDs, 6% solid material, and 50% silicate in the solid material show the strongest in vitro fluorescence and the highest thermal stability. In vivo monitoring of STB‐GQDs is also achieved through fluorescent imaging where incorporated GQDs exhibit a robust and stable signal, suggesting their promising applications in long‐term tracking of gelatin‐based STBs.

Oxygen (O-2) generating biomaterials are emerging as important compositions to improve our capabilities in supporting tissue engineering and regenerative therapeutics. Several in vitro studies demonstrated the usefulness of O-2 releasing biomaterials in enhancing cell survival and differentiation. However, more efforts are needed to develop materials that can provide sustained O-2 release for the long-term. In this paper, we present different O-2 generating sources, including hydrogen peroxide, sodium percarbonate, calcium peroxide and magnesium peroxide, and also cover types of carriers and relevant methods of fabricating O-2 generating systems. Then, the applications of O-2 generating materials in supporting engineered constructs, supplying high O-2 demanding cell transplants, and supporting ischemic tissues are discussed. Moreover, the challenges and future perspectives are highlighted.

Back pain is the second most common reason for primary-care physician visits after the common cold. New understanding of the spine pathophysiology and biomechanics led to the development of novel injectable biomaterials to treat those pain generators. Although not all biomaterials are currently ready for common use, there is significant interest by the medical community to invest time, resources, and energy to optimize these injectables. This review introduces basic concepts and advancements in the field of bioinjectables tailored for the vertebral body. Also, we highlight advances in injectable biomaterials which were presented at the Groupe de Recherche Interdisciplinaire sur les Biomatériaux Ostéoarticulaires Injectables (GRIBOI) (Interdisciplinary Research Society for Injectable Osteoarticular Biomaterials) meeting in March 2018 in Los Angeles, CA. Indeed, multidisciplinary translational research and international meetings such as GRIBOI bring together scientists and clinicians with different backgrounds/expertise to discuss injectable biomaterials innovations tailored for the interventional pain management field.

Irregular hemodynamics affects the progression of various vascular diseases, such atherosclerosis or aneurysms. Despite the extensive hemodynamics studies on animal models, the inter-species differences between humans and animals hamper the translation of such findings. Recent advances in vascular tissue engineering and the suitability of in vitro models for interim analysis have increased the use of in vitro human vascular tissue models. Although the effect of flow on endothelial cell (EC) pathophysiology and EC-flow interactions have been vastly studied in two-dimensional systems, they cannot be used to understand the effect of other micro- and macro-environmental parameters associated with vessel wall diseases. To generate an ideal in vitro model of the vascular system, essential criteria should be included: 1) the presence of smooth muscle cells or perivascular cells underneath an EC monolayer, 2) an elastic mechanical response of tissue to pulsatile flow pressure, 3) flow conditions that accurately mimic the hemodynamics of diseases, and 4) geometrical features required for pathophysiological flow. In this paper, we review currently available in vitro models that include flow dynamics and discuss studies that have tried to address the criteria mentioned above. Finally, we critically review in vitro fluidic models of atherosclerosis, aneurysm, and thrombosis.

Cell survival during the early stages of transplantation and before new blood vessels formation is a major challenge in translational applications of three-dimensional (3D) bioprinted tissues. Supplementing oxygen (O(2)) to transplanted cells via an O(2) generating source such as calcium peroxide (CPO) is an attractive approach to ensure cell viability. Calcium peroxide also produces calcium hydroxide which reduces the viscosity of bioinks, which is a limiting factor for bioprinting. Therefore, adapting this solution into 3D bioprinting is of significant challenge. In this study, we developed a gelatin methacryloyl (GelMA) bioink that was optimized in terms of pH and viscosity. The improved rheological properties led to the production of a robust bioink suitable for 3D bioprinting and controlled O(2) release. In addition, we characterized O(2) release, bioprinting conditions and mechanical performance of hydrogels having different CPO concentrations. As a proof of concept study, fibroblasts and cardiomyocytes were bioprinted using GelMA bioink containing CPO. Viability and metabolic activity of printed cells were checked after seven days of culture under hypoxic condition. The results showed that the addition of CPO improves the metabolic activity and viability of cells in bioprinted constructs under hypoxic condition.

The dermal papilla cell (DPC) is a type of highly specialized mesenchymal cells located in hair follicles (HF). Due to the primary role in the epithelial–mesenchymal interaction that enables hair-follicle morphogenesis and hair cycling, DPC has become an attractive cell source for hair regeneration to treat alopecia patients. However, DPCs tend to lose their function during in vitro culture. Hence, there exists a clear need to develop a microenvironment that can recapitulate the interactions within the native milieu of DPCs. Since layer-by-layer (LBL) nano-coating with biocompatible materials on the cell surface displays the versatility with tunable loading and release properties, which can provide a remodeled microenvironment for regulating cell function. Here, we developed a LBL self-assembly technique to single DPCs to create a nano-scale ultrathin extracellular matrix (ECM). We studied that the single cell-based LBL-encapsulation would not impact the viability, morphology, proliferation and intrinsic properties of DPCs using Western blot and mRNA expressions of β-catenin, ALP and α-SMA. We then included fibroblast growth factor-2 (FGF-2) into the LBL nano-structure to regulate the DPC function. Finally, we performed in vivo hair reconstitution assays using LBL-encapsulated DPCs combined with freshly isolated epidermal cells (EPCs) and found this strategy can treat hair loss.

Microphysiological systems, also known as organ-on-a-chip platforms, show promise for the development of new testing methods that can be more accurate than both conventional two-dimensional (2D) cultures and costly animal studies. The development of more intricate microphysiological systems can help to better mimic the human physiology and highlight the systemic effects of different drugs and materials. Nanomaterials are among a technologically important class of materials used for diagnostic, therapeutic, and monitoring purposes; all of which can be tested using new organ-on-a-chip systems. In addition, the toxicity of nanomaterials which have entered the body from ambient air or diet can have deleterious effects on various body systems. This in turn can be studied in newly developed microphysiological systems. While organ-on-a-chip models can be useful, they cannot pick up secondary and systemic toxicity. Thus, the utilization of multiorgan-on-a-chip systems for advancing nanotechnology will largely be reflected in the future of drug development, toxicology studies, and precision medicine. Various aspects of related studies, current challenges, and future perspectives are discussed in this paper.

Droplet-based microfluidic systems have been employed to manipulate discrete fluid volumes with immiscible phases. Creating the fluid droplets at microscale has led to a paradigm shift in mixing, sorting, encapsulation, sensing, and designing high throughput devices for biomedical applications. Droplet microfluidics has opened many opportunities in microparticle synthesis, molecular detection, diagnostics, drug delivery, and cell biology. In the present review, we first introduce standard methods for droplet generation (i.e. passive and active methods) and discuss the latest examples of emulsification and particle synthesis approaches enabled by microfluidic platforms. Then, the applications of droplet-based microfluidics in different biomedical applications are detailed. Finally, a general overview of the latest trends along with the perspectives and future potentials in the field are provided.

Tissue reconstruction requires the utilization of multiple biomaterials and cell types to replicate the delicate and complex structure of native tissues. Various three-dimensional (3D) bioprinting techniques have been developed to fabricate customized tissue structures; however, there are still significant challenges, such as vascularization, mechanical stability of printed constructs, and fabrication of gradient structures to be addressed for the creation of biomimetic and complex tissue constructs. One approach to address these challenges is to develop multimaterial 3D bioprinting techniques that can integrate various types of biomaterials and bioprinting capabilities towards the fabrication of more complex structures. Notable examples include multi-nozzle, coaxial, and microfluidics-assisted multimaterial 3D bioprinting techniques. More advanced multimaterial 3D printing techniques are expected to be developed, and new areas in this niche technology are rapidly evolving. In this review, we briefly introduce the basics of individual 3D bioprinting techniques and then discuss the multimaterial 3D printing techniques that can be developed based on these techniques for the engineering of complex and biomimetic tissue constructs. We also discuss the perspectives and future directions to develop state-of-the-art multimaterial 3D bioprinting techniques for engineering tissues and organs.

Viral infection is one of the leading causes of mortality worldwide. The growth of globalization significantly increases the risk of virus spreading, making it a global threat to future public health. In particular, the ongoing coronavirus disease 2019 (COVID‐19) pandemic outbreak emphasizes the importance of devices and methods for rapid, sensitive, and cost‐effective diagnosis of viral infections in the early stages by which their quick and global spread can be controlled. Micro and nanoscale technologies have attracted tremendous attention in recent years for a variety of medical and biological applications, especially in developing diagnostic platforms for rapid and accurate detection of viral diseases. This review addresses advances of microneedles, microchip‐based integrated platforms, and nano‐ and microparticles for sampling, sample processing, enrichment, amplification, and detection of viral particles and antigens related to the diagnosis of viral diseases. Additionally, methods for the fabrication of microchip‐based devices and commercially used devices are described. Finally, challenges and prospects on the development of micro and nanotechnologies for the early diagnosis of viral diseases are highlighted., Viral infections are the leading causes of mortality worldwide. Micro and nanoscale technologies have been used to develop diagnostic platforms for rapid and accurate detection of viral diseases. Here, these technologies are reviewed for sampling, sample processing, enrichment, amplification, and detection of viral particles and antigens. Challenges and future directions in this area are highlighted.

Microneedles (MNs) have been used to deliver drugs for over two decades. These platforms have been proven to increase transdermal drug delivery efficiency dramatically by penetrating restrictive tissue barriers in a minimally invasive manner. While much of the early development of MNs focused on transdermal drug delivery, this technology can be applied to a variety of other non-transdermal biomedical applications. Several variations, such as multi-layer or hollow MNs, have been developed to cater to the needs of specific applications. The heterogeneity in the design of MNs has demanded similar variety in their fabrication methods; the most common methods include micromolding and drawing lithography. Numerous materials have been explored for MN fabrication which range from biocompatible ceramics and metals to natural and synthetic biodegradable polymers. Recent advances in MN engineering have diversified MNs to include unique shapes, materials, and mechanical properties that can be tailored for organ-specific applications. In this review, we discuss the design and creation of modern MNs that aim to surpass the biological barriers of non-transdermal drug delivery in ocular, vascular, oral, and mucosal tissue.

Alginate hydrogels have been used in cell encapsulation for many years but a prevalent issue with pure alginates is that they are unable to provide enough bioactive properties to interact with mammalian cells. This paper discusses the modification of alginate with mussel-inspired dopamine for cell loading and anti-infection. Mouse bone marrow stem cells were immobilized into alginate and alginate-dopamine beads and fibers. Through live-dead and MTT assay, alginates modified by dopamine promoted cell viability and proliferation. In vitro cell differentiation results showed that such an alginate-dopamine gel can promote the osteogenic differentiation of mesenchymal stem cell after PCR and ALP assays. In addition to that, the adhesive prosperities of dopamine allowed for coating the surface of alginate-dopamine gel with silver nanoparticles, which provided the gel with significant antibacterial characteristics. Overall, these results demonstrate that a dopamine-modified alginate gel can be a great tool for cell encapsulation to promote cell proliferation and can be applied to bone regeneration, especially in contaminated bone defects.

Presented herein is a comprehensive study on the size-dependent coupled longitudinal-transverse-rotational free vibration behavior of post-buckled functionally graded (FG) micro- and nano-beams based on the most general Mindlin's strain gradient theory. The current model enables us to incorporate size effects via introducing material length scale parameters and is developed in the framework of the first-order shear deformable beam model and the von Karman geometric nonlinearity. The FG micro- and nano-beams, whose volume fraction is expressed by using a power law function, are assumed to be made of a mixture of metals and ceramics. By using Hamilton's principle, the nonlinear governing equations and associated boundary conditions are derived for FG micro- and nano-beams in the postbuckling domain. Afterwards, the governing equations and boundary conditions are discretized using the generalized differential quadrature (GDQ) method in conjunction with a direct approach without linearization, before solving numerically by Newton's method. The effects of length scale parameter, length-to-thickness ratio, material gradient index and boundary conditions on the postbuckling path and frequency of FG micro- and nano-beams are carefully investigated. Finally, numerical results obtained from both the modified strain gradient theory (MSGT) and modified couple stress theory (MCST) are compared.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Activins are members of the superfamily of transforming growth factors and have many potential neuroprotective effects. Herein, at the first place, we verified activin B's neuroprotective role in a PD model, and revealed that activin B's fast release has limited function in the PD therapy. To this end, we developed a multi-functional crosslinker based thermosensitive injectable hydrogels to deliver activin B, and stereotactically injected the activin B-loaded hydrogel into the striatum of a mouse model of PD. The histological evaluation showed that activin B can be detected even 5 weeks post-surgery in PD mice implanted with activin B-loaded hydrogels, and activin B-loaded hydrogels can significantly increase the density of tyrosine hydroxylase positive (TH(+)) nerve fibers and reduce inflammatory responses. The behavioral evaluation demonstrated that activin B-loaded hydrogels significantly improved the performance of the mice in the PD model. Meanwhile, we found that hydrogels can slightly induce the activation of microglia cells and astrocytes, while cannot induce apoptosis in the striatum. Overall, our data demonstrated that the developed activin B-loaded hydrogels provide sustained release of activin B for over 5 weeks and contribute to substantial cellular protection and behavioral improvement, suggesting their potential as a therapeutic strategy for PD.

Polyaniline (PANI) is a promising pseudocapacitance electrode material. However, its structural instability leads to low cyclic stability and limited rate capability which hinders its practical applications. In view of the limitations, flexible PANI-based composite films are developed to improve the electrochemical performance of electrode materials. We report in the research a facile and cost-effective approach for fabrication of a high-performance supercapacitor (SC) with excellent cyclic stability and tunable energy and power densities. SC electrode containing a very high mass loading of active materials is a flexible film of PANI, tissue wiper-based cellulose, graphite-based exfoliated graphite (ExG), and silver nanoparticles with potential applications in wearable electronics. The optimum preparation weight ratios of silver nitrate/aniline and ExG/aniline used in the research are estimated to be 0.18 and 0.65 (or higher), respectively. Our results show that an ultrahigh capacitance of 3.84 F/cm(2) (240.10 F/g) at a discharge rate of 5 mA can be achieved. In addition, our study shows that the power density can be increased from 1531.3 to 3000 W/kg by selecting the weight ratio of ExG/aniline to be more than 0.65, with a sacrifice in the energy density. The obtained promising electrochemical properties are found to be mainly attributed to an effective combination of PANI, ExG, cushiony cellulose scaffold, and silver as well as the porosity of the composite.

The aim of this paper was to investigate the wave propagation of nanotubes conveying fluid by considering the surface stress effect. To this end, the nanotube is modeled as a Timoshenko nanobeam. According to the Gurtin–Murdoch continuum elasticity, the surface stress effect is incorporated into the governing equations of motion obtained from the Hamilton principle. The governing differential equations are solved by generalized differential quadrature method. Then, the effects of the thickness, material and surface stress modulus, residual surface stress, surface density and flow velocity on spectrum curves of nanotubes predicted by both classical and non-classical theories are studied. The first three fundamental modes including flexural, axial, and shear waves of nanotubes are considered.

Clinically, patches for hernia repair have two existing concerns: antibacterial and tissue adhesion. The modification of medical device surfaces with antibacterial properties has recently shown to be an effective means to control bacterial-caused infection. On the other hand, hydrogel of gelatin and polyethylene glycol (PEG) has been verified for reducing tissue adhesion. Herein, we report a novel muscle-inspired and nano-silver coated, polyethyleneglycol (PEG)/gelatin hydrogel-impregnated polyurethane (NSPU) mesh. We hypothesize that an outside coated nano-silver is antiseptic to inflammations and infection. The PEG and gelatin hydrogel can remarkably reduce the postoperative adhesion in the abdomen; moreover, the flexible nanofibrous PU provides the necessary mechanical support as well. The composite mesh exhibited good antibacterial property in vitro. In vivo, after the implantation, it significantly reduced the postoperative adhesion in the abdomen compared to commercial polypropylene (PP) meshes. The composite also shows the graft accommodation in the abdominal wall tissue from hematoxylin–eosin (H&E) staining and immunohistochemistry analysis of CD3 (lymphocyte), CCR7 (M1 phenotype macrophage) and CD163 (M2 phenotype macrophage). Therefore, our NSPU mesh is promising for ventral hernia repair.

Parkinson's disease (PD) is a long-term neurodegenerative disorders that characterized by a progressive loss of dopaminergic neurons in substantia nigra pars compacta (SNc). Bone marrow stromal cells (BMSCs) are promising therapeutic agents for neurodegenerative disease due to their multipotent capacity. To promote the potential therapeutic effect of BMSCs on PD, we developed an injectable Gelatin-PANI hydrogels as a novel carrier for delivering BMSCs to the SNc region in mice with PD by stereotactic injection. Histology results showed that the BMSCs-loaded hydrogels lead to increased numbers of tyrosine hydroxylase positive (TH+) dopaminergic neurons and fibers in the SNc and striatum, and increased expression of brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) in the SNc. Meanwhile, rotarod and open field evaluation demonstrated BMSCs-loaded hydrogels significantly improved the behavioral performance of PD mice. Importantly, BMSCs-loaded hydrogels imparted more sustained protective effects than BMSCs alone in PD mice. Overall, the current data indicate that the hydrogel serves as a promising carrier to deliver BMSCs to the SNc for the treatment of PD.

Presented in this work is a novel and facile approach to fabricate an elastic, attachable, and cost-efficient carbon nanotube (CNT)-based strain gauge which can be efficiently used as bodily motion sensors. An innovative and unique method is introduced to align CNTs without external excitations or any complicated procedure. In this design, CNTs are aligned and distributed uniformly on the entire chewing gum by multiple stretching and folding technique. The current sensor is demonstrated to be a linear strain sensor for at least strains up to 200% and can detect strains as high as 530% with a high sensitivity ranging from 12 to 25 and high durability. The gum sensor has been used as bodily motion sensors, and outstanding results are achieved; the sensitivity is quite high, capable of tracing slow breathing. Since the gum sensor can be patterned into various forms, it has wide applications in miniaturized sensors and biochips. Interestingly, we revealed that our gum sensor has the ability to monitor humidity changes with high sensitivity and fast resistance response capable of monitoring human breathing.

In this paper, the nonlinear bending and postbuckling characteristics of Mindlin rectangular microplates made of functionally graded (FG) materials are studied based on the modified couple stress theory (MCST). This theory facilitates considering size dependency through introducing material length scale parameters. The FG microplates, whose volume fraction is expressed by a power law function, are considered to be made of a mixture of metals and ceramics. By considering the physical neutral plane position, the stretching–bending coupling is eliminated in both nonlinear governing equations and boundary conditions of FG microplates. With the aid of MCST and the principle of virtual work, the governing equations and corresponding boundary conditions are derived. Then, the obtained governing equations and boundary conditions are discretized through the generalized differential quadrature (GDQ) method. Finally, the resulting nonlinear parameterized equations are solved by the pseudo-arclength continuation technique. The effects of material gradient index, length scale parameter, length-to-thickness ratio, and boundary conditions on the nonlinear bending and postbuckling responses of FG microplates are investigated.

Presented in this paper is a precise investigation of the effect of surface stress on the vibration characteristics and instability of fluid-conveying nanoscale pipes. To this end, the nanoscale pipe is modeled as a Timoshenko nanobeam. The equations of motion of the nanoscale pipe are obtained based on Hamilton’s principle and the Gurtin–Murdoch continuum elasticity incorporating the surface stress effect. Afterwards, the generalized differential quadrature method is employed to discretize the governing equations and associated boundary conditions. To what extent important parameters such as the thickness, material and surface stress modulus, residual surface stress, surface density, and boundary conditions influence the natural frequency of nanoscale pipes and the critical velocity of fluid is discussed.

Presented herein is a comprehensive investigation on the size-dependent pull-in instability of geometrically non-linear rectangular nanoplates including surface stress effects undergoing hydrostatic and electrostatic actuations. To this end, based on the Gurtin–Murdoch theory, a non-classical continuum plate model capable of incorporating size-effects is developed; then, by means of the principle of virtual work, the governing equations of the actuated nanoplate are obtained. Subsequently, the generalized differential quadrature (GDQ) method is used to discretize the governing equations and associated boundary conditions, before solving numerically by the pseudo arc-length algorithm. Finally, the influences of important parameters including the geometrical non-linearity, thickness of the nanoplate, surface elastic modulus, residual surface stress and boundary conditions on the pull-in behavior of the actuated nanoplate are thoroughly studied. In addition, the effect of the material on the pull-in voltage and pressure is investigated by comparing the results obtained from nanoplates made of two different materials including aluminum (Al) and silicon (Si).

Correction for ‘Hydrogels from natural egg white with extraordinary stretchability, direct-writing 3D printability and self-healing for fabrication of electronic sensors and actuators’ by Qiang Chang et al., J. Mater. Chem. A, 2019, DOI: 10.1039/c9ta06233e.

This article is aimed at developing a nonclassical Mindlin rectangular functionally graded material (FGM) microplate based on the strain gradient theory (SGT) to study the thermal buckling behavior of microplates with different boundary conditions. This theory comprises material length scale parameters to interpret size effects. The developed model encompasses classical and modified couple stress Mindlin microplate models, if all the material length scale parameters or two of them are taken to be zero, respectively. The Mindlin rectangular FGM microplate is considered to be made of a mixture of metal and ceramic of which the volume fraction is described through a power low function. According to Hamilton's principle and the generalized differential quadrature (GDQ) method, the stability equations and associated boundary conditions are obtained and discretized, respectively. Current formulations provide a possibility to have all types of boundary conditions which herein, FGM microplates with three commonly...

The thermal postbuckling characteristics of microbeams made of functionally graded materials (FGMs) undergoing thermal loads are investigated based on the modified strain gradient theory (MSGT). The volume fraction of the ceramic and metal phases of FGM microbeams is expressed by using a power low function. The non-classical beam model presented herein is capable of interpreting size effects through introducing material length scale parameters and encompasses the modified couple stress theory (MCST) and classical theory (CT). Based on the non-linear Timoshenko beam theory and the principle of virtual work, the stability equations and associated boundary conditions are derived and are then solved through the generalized differential quadrature (GDQ) method in conjunction with a direct approach without linearization. The influences of the material gradient index, length scale parameter, and boundary conditions on the thermal postbuckling behavior of FGM microbeams are comprehensively investigated. Also, this study compares the results obtained from the MSGT with those from CT. The effect of geometrical imperfection on the buckling deformation of microbeams in prebuckled and postbuckled states is discussed.

Yi Kong,1,2,* Rui Xu,1,* Mohammad Ali Darabi,2 Wen Zhong,3 Gaoxing Luo,1 Malcolm MQ Xing,1,2 Jun Wu1 1Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns, and Combined Injury, Chongqing Key Laboratory for Diseases Proteomics, Third Military Medical University, Chongqing, People’s Republic of China; 2Department of Mechanical Engineering, Biochemistry and Medical Genetics, Children’s Hospital Research Institute of Manitoba, 3Department of Biosystem Engineering, University of Manitoba, Winnipeg, MB, Canada *These authors contributed equally to this work Abstract: Polymeric ultrathin membranes that are compatible with cells offer tremendous advantages for tissue engineering. In this article, we report a free-standing nanomembrane that was developed using a layer-by-layer self-assembly technique with a safe and sacrificial substrate method. After ionization, two oppositely charged polyelectrolytes, alginate and chitosan, were alternately deposited on a substrate of a solidified gelatin block to form an ultrathin nanomembrane. The space between the two adjacent layers was ~200nm. The thickness of the nanomembrane was proportional to the number of layers. The temperature-sensitive gelatin gel served as a sacrificial template at 37°C. The free-standing nanomembrane promoted bone marrow stem cell adhesion and proliferation. Fluorescence-activated cell sorting was used to analyze green-fluorescent-protein-positive mesenchymal stem cells from the wounds, which showed a significantly high survival and proliferation from the nanomembrane when cells were transplanted to mouse dorsal skin that had a full-thickness burn. The bone-marrow-stem-cell-loaded nanomembrane also accelerated wound contraction and epidermalization. Therefore, this methodology provides a fast and facile approach to construct free-standing ultrathin scaffolds for tissue engineering. The biocompatibility and free-standing nature of the fabricated nanomembrane may be particularly useful for stem cell delivery and wound healing. Keywords: nanomembrane, layer-by-layer, cell delivery, wound healing

Hai Zhuang,1–3 Shoushan Bu,1 Lei Hua,1 Mohammad A Darabi,2,3 Xiaojian Cao,4 Malcolm Xing2,3 1Department of Stomatology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 2Department of Mechanical Engineering, Biochemistry & Medical Genetics, 3Children’s Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB, Canada; 4Department of Orthopedics, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic ofChina Abstract: In this study, we fabricated glial cell-line derived neurotrophic factor (GDNF)-loaded microspheres, then seeded the microspheres in gelatin-methacrylamide hydrogel, which was finally integrated with the commercial bilayer collagen membrane (Bio-Gide®). The novel composite of nerve conduit was employed to bridge a 10mm long sciatic nerve defect in a rat. GDNF-loaded gelatin microspheres had a smooth surface with an average diameter of 3.9±1.8µm. Scanning electron microscopy showed that microspheres were uniformly distributed in both the GelMA gel and the layered structure. Using enzyme-linked immunosorbent assay, in vitro release studies (pH 7.4) of GDNF from microspheres exhibited an initial burst release during the first 3days (18.0%±1.3%), and then, a prolonged-release profile extended to 32days. However, in an acidic condition (pH 2.5), the initial release percentage of GDNF was up to 91.2%±0.9% within 4hours and the cumulative release percentage of GDNF was 99.2%±0.2% at 48hours. Then the composite conduct was implanted in a 10mm critical defect gap of sciatic nerve in a rat. We found that the nerve was regenerated in both conduit and autograft (AG) groups. A combination of electrophysiological assessment and histomorphometry analysis of regenerated nerves showed that axonal regeneration and functional recovery in collagen tube filled with GDNF-loaded microspheres (GM + CT) group were similar to AG group (P>0.05). Most myelinated nerves were matured and arranged densely with a uniform structure of myelin in a neat pattern along the long axis in the AG and GM + CT groups, however, regenerated nerve was absent in the BLANK group, left the 10 mm gap empty after resection, and the nerve fiber exhibited a disordered arrangement in the collagen tube group. These results indicated that the hybrid system of bilayer collagen conduit and GDNF-loaded gelatin microspheres combined with gelatin-methacrylamide hydrogels could serve as a new biodegradable artificial nerve guide for nerve tissue engineering. Keywords: controlled release of GDNF, gelatin microspheres, biodegradable nerve conduit, gelatin-methacrylamide hydrogel, sciatic nerve regeneration

A strategy utilizing elastin peptide macroporous cryogels to build highly flexible scaffolds to load carbon nanotubes, polypyrrole, and iron oxide magnetic nanoparticles, is presented. This combines high elasticity, flexibility, shape memory property, and injectable property together with conductivity and/or magnetic responsive property. The network can afford 97.5% compressive strain with an excellent conductivity of 50.1 ± 2.9 S cm(-1) at 90% strain.

This paper is aimed to examine the geometrically nonlinear vibration and stability of nanoscale pipe conveying fluid incorporating surface stress effect. To approach this, the von-Karman hypothesis and Timoshenko beam theory are used to model the nanoscale pipe as a nonlinear Timoshenko nanobeam. Then, Hamilton’s principle and the Gurtin–Murdoch continuum elasticity are used to derive the governing equations of motion and associated boundary conditions incorporating the surface stress effect. Afterward, by the generalized differential quadrature method and harmonic balance method, the obtained nonlinear differential equations are discretized and simplified, before solving numerically through the Newton–Raphson method. The effects of the surface stress parameters on the stability and imaginary and real parts of frequency of nanopipes are discussed. Results are performed for nanopipes with different end supports made of silicon (Si) and aluminum (Al).

This paper investigates the large-amplitude free vibration of a double-walled carbon nanotube (DWCNT) surrounded by an elastic medium in the presence of temperature change. Based on continuum mechanics, a nonlocal elastic beam model is employed in which nanotubes are coupled together via the van der Waals (vdW) interlayer interactions. The Pasternak foundation model and a nonlinear vdW model are utilized to describe the surrounding elastic medium effect and the vdW interlayer interactions, respectively. DWCNTs with different boundary conditions are analyzed utilizing the Timoshenko beam theory that considers the shear deformation and rotary inertia effects. The governing equations are derived from Hamilton’s principle; the Galerkin method is utilized to discretize the governing equations. The influences of the nonlocal parameter, spring constant, carbon nanotube aspect ratio, and temperature change on the nonlinear free vibration characteristics of a double-walled carbon nanotube with different boundary conditions are thoroughly investigated. It is deduced that the nonlocal parameter, spring constant, and the aspect ratio play significant roles for the value of the nonlinear frequency. Also, the temperature change and the type of boundary conditions have an effect on the nonlinear frequency.

Free vibrations of a beam-mass-spring system with different boundary conditions are analyzed both analytically and numerically. In the analytical analysis, the system is divided into three subsystems and the effects of the spring and the point mass are considered as internal boundary conditions between any two neighboring subsystems. The partial differential equations governing the motion of the subsystems and internal boundary conditions are then solved using the method of separation of variables. In the numerical analysis, the whole system is considered as a single system and the effects of the spring and point mass are introduced using the Dirac delta function. The Galerkin method is then employed to discretize the equation of motion and the resulting set of ordinary differential equations are solved via eigenvalue analysis. Analytical and numerical results are shown to be in very good agreement.

In this paper, the thermal buckling behavior of single-walled carbon nanotubes (SWCNTs) embedded in an elastic medium is studied. To this end, the SWCNTs are modeled based on the nonlocal Timoshenko beam theory into which the effect of the elastic medium is incorporated The generalized differential quadrature (GDQ) method is employed to discretize the governing differential equations and to consider different commonly used boundary conditions (BCs). For simply supported BCs, the results obtained from the present analysis are compared with the ones from the exact solution and an excellent agreement has been achieved. The effects of the aspect ratio, nonlocal parameter and the Winkler parameter on the dimensionless critical buckling temperature are carefully investigated.

The subject of this paper is the development of a general solution procedure for the vibrations (primary resonance and nonlinear natural frequency) of systems with cubic nonlinearities, subjected to nonlinear and time-dependent internal boundary conditions—this is a commonly occurring situation in the vibration analysis of continuous systems with intermediate elements. The equations of motion form a set of nonlinear partial differential equations with nonlinear, time-dependent, and coupled internal boundary conditions. The method of multiple timescales, an approximate analytical method, is applied directly to each partial differential equation of motion as well as coupled boundary conditions (i.e. on each sub-domain and the corresponding internal boundary conditions for a continuous system with intermediate elements) which ultimately leads to approximate analytical expressions for the frequency–response relation and nonlinear natural frequencies of the system. These closed-form solutions provide direct insight into the relationship between the system parameters and vibration characteristics of the system. Moreover, the suggested solution procedure is applied to a sample problem which is discussed in detail.

The aim of this study is to develop an approximate analytic solution for nonlinear dynamic response of a simply-supported Kelvin- Voigt viscoelastic beam with an attached heavy intra-span mass. A geometric nonlinearity due to midplane stretching is considered and Newton's second law of motion along with Kelvin-Voigt rheological model, which is a two-parameter energy dissipation model, are employed to derive the nonlinear equations of motion. The method of multiple timescales is applied directly to the governing equations of motion, and nonlinear natural frequencies and vibration responses of the system are obtained analytically. Regarding the resonance case, the limit-cycle of the response is formulated analytically. A parametric study is conducted in order to highlight the influences of the system parameters. The main objective is to examine how the vibration response of a plain (i.e. without additional adornment) beam is modified by the presence of a heavy mass, attached somewhere along the beam length.