Graphene and its chemical derivatives have been a pivotal new class of nanomaterials and a model system for quantum behavior. The material's excellent electrical conductivity, biocompatibility, surface area and thermal properties are of much interest to the scientific community. Two dimensional graphene materials have been widely used in various biomedical research areas such as bioelectronics, imaging, drug delivery, and tissue engineering. In this review we will highlight the recent applications of graphene-based materials in tissue engineering and regenerative medicine. In particular, we will discuss the application of graphene-based materials in cardiac, neural, bone, cartilage, skeletal muscle, and skin/adipose tissue engineering. We also discuss the potential risk factors of graphene-based materials in tissue engineering. In addition, we will outline the opportunities in the usage of graphene-based materials for clinical applications.
Bioprinting is the most convenient microfabrication method to create biomimetic three-dimensional (3D) cardiac tissue constructs, which can be used to regenerate damaged tissue and provide platforms for drug screening. However, existing bioinks, which are usually composed of polymeric biomaterials, are poorly conductive and delay efficient electrical coupling between adjacent cardiac cells. To solve this problem, we developed a gold nanorod (GNR) incorporated gelatin methacryloyl (GelMA)-based bioink for printing 3D functional cardiac tissue constructs. The GNR concentration was adjusted to create a proper microenvironment for the spreading and organization of cardiac cells. At optimized concentration of GNR, the nanocomposite bioink had a low viscosity, similar to pristine inks, which allowed for the easy integration of cells at high densities. As a result, rapid deposition of cell-laden fibers at a high resolution was possible, while reducing shear stress on the encapsulated cells. In the printed GNR constructs, cardiac cells showed improved cell adhesion and organization when compared to the constructs without GNRs. Furthermore, the incorporated GNRs bridged the electrically resistant pore walls of polymers, improved the cell-to-cell coupling, and promoted synchronized contraction of the bioprinted constructs. Given its advantageous properties, this gold nanocomposite bioink may find wide application in cardiac tissue engineering.
Periodontitis is a prevalent chronic, destructive inflammatory disease affecting tooth-supporting tissues in humans. Guided tissue regeneration strategies are widely utilized for periodontal tissue regeneration generally by using a periodontal membrane. The main role of these membranes is to establish a mechanical barrier that prevents the apical migration of the gingival epithelium and hence allowing the growth of periodontal ligament and bone tissue to selectively repopulate the root surface. Currently available membranes have limited bioactivity and regeneration potential. To address such challenges, an osteoconductive, antibacterial, and flexible poly(caprolactone) (PCL) composite membrane containing zinc oxide (ZnO) nanoparticles is developed. The membranes are fabricated through electrospinning of PCL and ZnO particles. The physical properties, mechanical characteristics, and in vitro degradation of the engineered membrane are studied in detail. Also, the osteoconductivity and antibacterial properties of the developed membrane are analyzed in vitro. Moreover, the functionality of the membrane is evaluated with a rat periodontal defect model. The results confirmed that the engineered membrane exerts both osteoconductive and antibacterial properties, demonstrating its great potential for periodontal tissue engineering.
Tissue engineering has the potential to revolutionize the health care industry. Delivering on this promise requires the generation of efficient, controllable and predictable implants. The integration of nano- and microtechnologies into macroscale regenerative biomaterials is playing an essential role in the generation of such implants, by enabling spatiotemporal control of the cellular microenvironment. Here we review the role, function and progress of a wide range of nano- and microtechnologies that are driving the advancements in the field of tissue engineering.
Nanoparticles have been used for engineering composite materials to improve the intrinsic properties and/or add functionalities to pristine polymers. The majority of the studies have focused on the incorporation of spherical nanoparticles within the composite fibers. Herein, we incorporate anisotropic branched-shaped zinc oxide (ZnO) nanoparticles into fibrous scaffolds fabricated by electrospinning. The addition of the branched particles resulted in their protrusion from fibers, mimicking the architecture of a rose stem. We demonstrated that the encapsulation of different-shape particles significantly influences the physicochemical and biological activities of the resultant composite scaffolds. In particular, the branched nanoparticles induced heterogeneous crystallization of the polymeric matrix and enhance the ultimate mechanical strain and strength. Moreover, the three-dimensional (3D) nature of the branched ZnO nanoparticles enhanced adhesion properties of the composite scaffolds to the tissues. In addition, the rose stem-like constructs offered excellent antibacterial activity, while supporting the growth of eukaryote cells.
Liquid-crystal-based biomaterials provide promising platforms for the development of dynamic and responsive interfaces for tissue engineering. Cholesteryl ester liquid crystals (CLCs) are particularly well suited for these applications, due to their roles in cellular homeostasis and their intrinsic ability to organize into supramolecular helicoidal structures on the mesoscale. Here, we developed a nonwoven CLC electrospun scaffold by dispersing three cholesteryl esterbased mesogens within polycaprolactone (PCL). We tuned the ratio of our mesogens so that the CLC would be in the mesophase at the cell culture incubator temperature of 37 °C. In these scaffolds, the PCL polymer provided an elastic bulk matrix while the homogeneously dispersed CLC established a viscoelastic fluidlike interface. Atomic force microscopy revealed that the 50% (w/v) cholesteryl ester liquid crystal scaffold (CLC-S) exhibited a mesophase with topographic striations typical of liquid crystals. Additionally, the CLC-S favorable wettability and ultrasoft fiber mechanics enhanced cellular attachment and proliferation. Increasing the CLC concentration within the composites enhanced myoblast adhesion strength promoted myofibril formation in vitro with mouse myoblast cell lines.
Nature generates densely packed micro-and nanostructures to enable key functionalities in cells, tissues, and other materials. Current fabrication techniques, due to limitations in resolution and speed, are far less effective at creating microstructures. Yet, the development of extensive amounts of surface area per unit volume will enable applications and manufacturing strategies not possible today. Here, we introduce chaotic printing-the use of chaotic flows for the rapid generation of complex, high-resolution microstructures. A simple and deterministic chaotic flow is induced in a viscous liquid, and its repeated stretching and folding action deforms an ''ink'' (i.e., a drop of a miscible liquid, fluorescent beads, or cells) at an exponential rate to render a densely packed lamellar microstructure that is then preserved by curing or photocrosslinking.This exponentially fast creation of fine microstructures exceeds the limits of resolution and speed of the currently available 3D printing techniques. Moreover, we show that the architecture of the microstructure to be created with chaotic printing can be predicted by mathematical modelling. We envision diverse applications for this technology, including the development of densely packed catalytic surfaces and highly complex multi-lamellar and multi-component tissue-like structures for biomedical and electronics applications. Conceptual insightsThis communication presents a simple, effective, and novel printing technique-one that is rooted in chaos theory and, more precisely, in the physics of chaotic mixing in a laminar regime. The main strength and differential attribute of this novel microfabrication strategy is its ability to create a densely packed microstructure at high resolution and speed in a predictable manner. Moreover, chaotic flows are deterministic, therefore, they are amenable to rigorous modeling and the microstructure resulting from them can be predicted using computational fluid dynamics platforms. In chaotic printing, a drop of ''ink'' (i.e., a drop of a miscible liquid, nanoparticles, or cells) is injected into a viscous and Newtonian soldifiable liquid. A chaotic flow is then applied to generate a very complex microstructure at an exponential rate, which is then preserved by a crosslinking or curing step. This exponentially fast creation of a linear structure (meters), and the accompanying rapid decrease in the length scales of the micro-and even nano-structure, is not currently achievable by any other 3D printing technique. We envision the use of this platform for many relevant applications such as the fabrication of complex tissues, catalytic surfaces, supercapacitors, and highly reinforced materials, among others.
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