Void‐Free 3D Bioprinting for In Situ Endothelialization and Microfluidic Perfusion

Two major challenges of 3D bioprinting are the retention of structural fidelity and efficient endothelialization for tissue vascularization. Both of these issues are addressed by introducing a versatile 3D bioprinting strategy, in which a templating bioink is deposited layer‐by‐layer alongside a matrix bioink to establish void‐free multimaterial structures. After crosslinking the matrix phase, the templating phase is sacrificed to create a well‐defined 3D network of interconnected tubular channels. This void‐free 3D printing (VF‐3DP) approach circumvents the traditional concerns of structural collapse, deformation, and oxygen inhibition, moreover, it can be readily used to print materials that are widely considered “unprintable.” By preloading endothelial cells into the templating bioink, the inner surface of the channels can be efficiently cellularized with a confluent endothelial layer. This in situ endothelialization method can be used to produce endothelium with a far greater cell seeding uniformity than can be achieved using the conventional postseeding approach. This VF‐3DP approach can also be extended beyond tissue fabrication and toward customized hydrogel‐based microfluidics and self‐supported perfusable hydrogel constructs.     

Layer‐by‐Layer Assembly of 3D Tissue Constructs with Functionalized Graphene

Carbon‐based nanomaterials have been considered promising candidates to mimic certain structure and function of native extracellular matrix materials for tissue engineering. Significant progress has been made in fabricating carbon nanoparticle‐incorporated cell culture substrates, but only a limited number of studies have been reported on the development of 3D tissue constructs using these nanomaterials. Here, a novel approach to engineer 3D multilayer constructs using layer‐by‐layer (LbL) assembly of cells separated with self‐assembled graphene oxide (GO)‐based thin films is presented. The GO‐based structures are shown to serve as cell adhesive sheets that effectively facilitate the formation of multilayer cell constructs with interlayer connectivity. By controlling the amount of GO deposited in forming the thin films, the thickness of the multilayer tissue constructs could be tuned with high cell viability. Specifically, this approach could be useful for creating dense and tightly connected cardiac tissues through the co‐culture of cardiomyocytes and other cell types. In this work, the fabrication of stand‐alone multilayer cardiac tissues with strong spontaneous beating behavior and programmable pumping properties is demonstrated. Therefore, this LbL‐based cell construct fabrication approach, utilizing GO thin films formed directly on cell surfaces, has great potential in engineering 3D tissue structures with improved organization, electrophysiological function, and mechanical integrity.     

Monodispersed Gold Nanorod‐Embedded Silica Particles as Novel Raman Labels for Biosensing

Biocompatible, photostable, and multiplexing‐compatible surface‐enhanced Raman spectroscopic tagging materials have been developed that are composed of gold nanorod (GNR)‐embedded silica particles and organic Raman labels. GNR‐embedded silica particles were prepared with different surface coverage by the assembly of GNRs on silica particles based on an electrostatic interaction and subsequent coating of silica with controllable thickness. This method allows the incorporation of various organic Raman labels to generate intense surface‐enhanced Raman scattering (SERS) spectra. Furthermore, SERS‐active particles are demonstrated as novel Raman tags for immunoassay. The results suggest SERS tags can be used for multiplex and ultrasensitive detection of biomolecules.     

Hybrid 3D Printing of Synthetic and Cell‐Laden Bioinks for Shape Retaining Soft Tissue Grafts

Despite recent advances in clinical procedures, the repair of soft tissue remains a reconstructive challenge. Current technologies such as synthetic implants and dermal flap autografting result in inefficient shape retention and unpredictable aesthetic outcomes. 3D printing, however, can be leveraged to produce superior soft tissue grafts that allow enhanced host integration and volume retention. Here, a novel dual bioink 3D printing strategy is presented that utilizes synthetic and natural materials to create stable, biomimetic soft tissue constructs. A double network ink composed of covalently cross‐linked poly(ethylene) glycol and ionically cross‐linked alginate acts as a physical support network that promotes cell growth and enables long‐term graft shape retention. This is coupled with a cell‐laden, biodegradable gelatin methacrylate bioink in a hybrid printing technique, and the composite scaffolds are evaluated in their mechanical properties, shape retention, and cytotoxicity. Additionally, a new shape analysis technique utilizing CloudCompare software is developed that expands the available toolbox for assessing scaffold aesthetic properties. With this dynamic 3D bioprinting strategy, complex geometries with robust internal structures can be easily modulated by varying the print ratio of nondegradable to sacrificial strands. The versatility of this hybrid printing fabrication platform can inspire the design of future multimaterial regenerative implants.     

Bioprinting Complex Cartilaginous Structures with Clinically Compliant Biomaterials

Bioprinting is an emerging technology for the fabrication of patient‐specific, anatomically complex tissues and organs. A novel bioink for printing cartilage grafts is developed based on two unmodified FDA‐compliant polysaccharides, gellan and alginate, combined with the clinical product BioCartilage (cartilage extracellular matrix particles). Cell‐friendly physical gelation of the bioink occurs in the presence of cations, which are delivered by co‐extrusion of a cation‐loaded transient support polymer to stabilize overhanging structures. Rheological properties of the bioink reveal optimal shear thinning and shear recovery properties for high‐fidelity bioprinting. Tensile testing of the bioprinted grafts reveals a strong, ductile material. As proof of concept, 3D auricular, nasal, meniscal, and vertebral disk grafts are printed based on computer tomography data or generic 3D models. Grafts after 8 weeks in vitro are scanned using magnetic resonance imaging and histological evaluation is performed. The bioink containing BioCartilage supports proliferation of chondrocytes and, in the presence of transforming growth factor beta‐3, supports strong deposition of cartilage matrix proteins. A clinically compliant bioprinting method is presented which yields patient‐specific cartilage grafts with good mechanical and biological properties. The versatile method can be used with any type of tissue particles to create tissue‐specific and bioactive scaffolds.     

Photosynthetic Cyanobacteria can Clearly Induce Efficient Muscle Tissue Regeneration of Bioprinted Cell-Constructs

Tissue engineering strategies using cell-laden constructs have shown promising results in the treatment of various types of damaged tissues. However, inadequate oxygen delivery to the macroscale 3D cell-constructs for regenerating skeletal muscle tissue has remained a multiplex issue owing to the pivotal factors including cell metabolism and several regulatory intercellular pathways that eventually influence various cellular activities and determines cell phenotype. To overcome this issue, a photosynthetic cyanobacterium (Synechococcus elongatus) is employed in a methacrylated gelatin bioink. Furthermore, to effectively induce cell alignment in the bioink, in situ electric field stimulation is used in a bioprinting system to fabricate cell-laden scaffolds for regenerating skeletal muscle tissue. Owing to the synergistic effects of the bioactive microenvironment that rescues cells from hypoxic conditions and activations of voltage-gated ion channels, highly aligned, multi-nucleated myofibers are obtained as well as significant upregulation (7–10-fold) of myogenic-related genes compared with conventionally prepared cell-constructs. In addition, in vivo studies using a mouse volumetric muscle loss model demonstrate considerable restoration of muscle functionality and regeneration.     

Tissue Engineered Bio‐Blood‐Vessels Constructed Using a Tissue‐Specific Bioink and 3D Coaxial Cell Printing Technique: A Novel Therapy for Ischemic Disease

Endothelial progenitor cells (EPCs) are a promising cell source for the treatment of several ischemic diseases for their potentials in neovascularization. However, the application of EPCs in cell‐based therapy has shown low therapeutic efficacy due to hostile tissue conditions after ischemia. In this study, a bio‐blood‐vessel (BBV) is developed, which is produced using a novel hybrid bioink (a mixture of vascular‐tissue‐derived decellularized extracellular matrix (VdECM) and alginate) and a versatile 3D coaxial cell printing method for delivering EPC and proangiogenic drugs (atorvastatin) to the ischemic injury sites. The hybrid bioink not only provides a favorable environment to promote the proliferation, differentiation, and neovascularization of EPCs but also enables a direct fabrication of tubular BBV. By controlling the printing parameters, the printing method allows to construct BBVs in desired dimensions, carrying both EPCs and atorvastatin‐loaded poly(lactic‐co‐glycolic) acid microspheres. The therapeutic efficacy of cell/drug‐laden BBVs is evaluated in an ischemia model at nude mouse hind limb, which exhibits enhanced survival and differentiation of EPCs, increased rate of neovascularization, and remarkable salvage of ischemic limbs. These outcomes suggest that the 3D‐printed ECM‐mediated cell/drug implantation can be a new therapeutic approach for the treatment of various ischemic diseases.     

Bioprinting of Cartilaginous Auricular Constructs Utilizing an Enzymatically Crosslinkable Bioink

Bioprinting of functional tissues could overcome tissue shortages and allow a more rapid response for treatments. However, despite recent progress in bioprinting, and its outstanding ability to position cells and biomaterials in a precise 3D manner, its success has been limited, due to insufficient maturation of constructs into functional tissue. Here, a novel calcium-triggered enzymatic crosslinking (CTEC) mechanism for bioinks based on the activation cascade of Factor XIII is presented and utilized for the biofabrication of cartilaginous constructs. Hyaluronan transglutaminase (HA-TG), an enzymatically crosslinkable material, has shown excellent characteristics for chondrogenesis and builds the basis of the CTEC bioink. The bioink supports tissue maturation with neocartilage formation and stiffening of constructs up to 400 kPa. Bioprinted constructs remain stable in vivo for 24 weeks and bioprinted auricular constructs transform into cartilaginous grafts. A major limitation of the current study is the deposition of collagen I, indicating the maturation toward fibrocartilage rather than elastic cartilage. Shifting the maturation process toward elastic cartilage will therefore be essential in order for the developed bioinks to offer a novel tissue engineered treatment for microtia patients. CTEC bioprinting furthermore opens up use of enzymatically crosslinkable biopolymers and their modularity to support a multitude of tissues.     

3D Bioprinting using UNIversal Orthogonal Network (UNION) Bioinks

Three-dimensional (3D) bioprinting is a promising technology to produce tissue-like structures, but a lack of diversity in bioinks is a major limitation. Ideally each cell type would be printed in its own customizable bioink. To fulfill this need for a universally applicable bioink strategy, a versatile bioorthogonal bioink crosslinking mechanism that is cell compatible and works with a range of polymers is developed. This family of materials is termed UNIversal, Orthogonal Network (UNION) bioinks. As demonstration of UNION bioink versatility, gelatin, hyaluronic acid (HA), recombinant elastin-like protein (ELP), and polyethylene glycol (PEG) are each used as backbone polymers to create inks with storage moduli spanning from 200 to 10 000 Pa. Because UNION bioinks are crosslinked by a common chemistry, multiple materials can be printed together to form a unified, cohesive structure. This approach is compatible with any support bath that enables diffusion of UNION crosslinkers. Both matrix-adherent human corneal mesenchymal stromal cells and non-matrix-adherent human induced pluripotent stem cell-derived neural progenitor spheroids are printed with UNION bioinks. The cells retained high viability and expressed characteristic phenotypic markers after printing. Thus, UNION bioinks are a versatile strategy to expand the toolkit of customizable materials available for 3D bioprinting.     

Modeling, Analysis, and Design of Graphene Nano-Ribbon Interconnects

Graphene nanoribbons (GNRs) are considered as a prospective interconnect material. A comprehensive conductance and delay analysis of GNR interconnects is presented in this paper. Using a simple tight-binding model and the linear response Landauer formula, the conductance model of GNR is derived. Several GNR structures are examined, and the conductance among them and other interconnect materials [e.g., copper (Cu), tungsten (W), and carbon nanotubes (CNTs)] is compared. The impact of different model parameters (i.e., bandgap, mean free path, Fermi level, and edge specularity) on the conductance is discussed. Both global and local GNR interconnect delays are analyzed using an RLC equivalent circuit model. Intercalation doping for multilayer GNRs is proposed, and it is shown that in order to match (or better) the performance of Cu or CNT bundles at either the global or local level, multiple zigzag-edged GNR layers along with proper intercalation doping must be used and near-specular nanoribbon edge should be achieved. However, intercalation-doped multilayer zigzag GNRs can have better performance than that of W, implying possible application as local interconnects in some cases. Thus, this paper identifies the on-chip interconnect domains where GNRs can be employed and provides valuable insights into the process technology development for GNR interconnects.      

Evaluation of the Biocompatibility of PLACL/Collagen Nanostructured Matrices with Cardiomyocytes as a Model for the Regeneration of Infarcted Myocardium

Pioneering research suggests various modes of cellular therapeutics and biomaterial strategies for myocardial tissue engineering. Despite several advantages, such as safety and improved function, the dynamic myocardial microenvironment prevents peripherally or locally administered therapeutic cells from homing and integrating of biomaterial constructs with the infarcted heart. The myocardial microenvironment is highly sensitive due to the nanoscale cues that it exerts to control bioactivities, such as cell migration, proliferation, differentiation, and angiogenesis. Nanoscale control of cardiac function has not been extensively analyzed in the field of myocardial tissue engineering. Inspired by microscopic analysis of the ventricular organization in native tissue, a scalable in‐vitro model of nanoscale poly(L ‐lactic acid)‐co ‐poly(? ‐caprolactone)/collagen biocomposite scaffold is fabricated, with nanofibers in the order of 594 ± 56 nm to mimic the native myocardial environment for freshly isolated cardiomyocytes from rabbit heart, and the specifically underlying extracellular matrix architecture: this is done to address the specificity of the underlying matrix in overcoming challenges faced by cellular therapeutics. Guided by nanoscale mechanical cues provided by the underlying random nanofibrous scaffold, the tissue constructs display anisotropic rearrangement of cells, characteristic of the native cardiac tissue. Surprisingly, cell morphology, growth, and expression of an interactive healthy cardiac cell population are exquisitely sensitive to differences in the composition of nanoscale scaffolds. It is shown that suitable cell–material interactions on the nanoscale can stipulate organization on the tissue level and yield novel insights into cell therapeutic science, while providing materials for tissue regeneration.     

Nanostructured Biomaterials for Regeneration

Biomaterials play a pivotal role in regenerative medicine, which aims to regenerate and replace lost/dysfunctional tissues or organs. Biomaterials (scaffolds) serve as temporary 3D substrates to guide neo tissue formation and organization. It is often beneficial for a scaffolding material to mimic the characteristics of extracellular matrix (ECM) at the nanometer scale and to induce certain natural developmental or/and wound healing processes for tissue regeneration applications. This article reviews the fabrication and modification technologies for nanofibrous, nanocomposite, and nanostructured drug‐delivering scaffolds. ECM‐mimicking nanostructured biomaterials have been shown to actively regulate cellular responses including attachment, proliferation, differentiation, and matrix deposition. Nanoscaled drug delivery systems can be successfully incorporated into a porous 3D scaffold to enhance the tissue regeneration capacity. In conclusion, nanostructured biomateials are a very exciting and rapidly expanding research area, and are providing new enabling technologies for regenerative medicine.     

Specific Near‐IR Absorption Imaging of Glioblastomas Using Integrin‐Targeting Gold Nanorods

Molecular imaging using nanoprobes with high resolution and low toxicity is essential in early cancer detection. Here we introduce a new class of smart imaging probes employing PEGylated gold nanorods (GNRs) conjugated to cRGD for specific optical imaging of α_vβ₃ integrins from glioblastoma. GNRs exhibiting an optical resonance peak in the near‐infrared (NIR) region were synthesized using the seed‐mediated growth method. CTAB (cetyl trimethylammonium bromide) bilayer on the GNRs was replaced with a biocompatible stabilizer, heterobifunctional polyethyleneglycol (COOH‐PEG‐SH). Further, the carboxylated GNRs (PGNRs; PEG‐coated GNRs) were functionalized with cRGD using EDC‐NHS chemistry to formulate cRGD‐conjugated GNRs (cRGD‐PGNRs) for α_vβ₃ integrins. In order to assess the potential of the cRGD‐PGNRs as a targeted imaging probe, we investigated their optical properties, biocompatibility, colloidal stability and in vitro/in vivo binding affinities for cancer cells. Consequently, cRGD‐PGNRs demonstrated excellent tumor targeting ability with no cytotoxicity, as well as sufficient cellular uptake due to stable and prolonged blood circulation of cRGD‐PGNRs.     

Nonmulberry Silk Based Ink for Fabricating Mechanically Robust Cardiac Patches and Endothelialized Myocardium‐on‐a‐Chip Application

Bioprinting holds great promise toward engineering functional cardiac tissue constructs for regenerative medicine and as drug test models. However, it is highly limited by the choice of inks that require maintaining a balance between the structure and functional properties associated with the cardiac tissue. In this regard, a novel and mechanically robust biomaterial‐ink based on nonmulberry silk fibroin protein is developed. The silk‐based ink demonstrates suitable mechanical properties required in terms of elasticity and stiffness (≈40 kPa) for developing clinically relevant cardiac tissue constructs. The ink allows the fabrication of stable anisotropic scaffolds using a dual crosslinking method, which are able to support formation of aligned sarcomeres, high expression of gap junction proteins as connexin‐43, and maintain synchronously beating of cardiomyocytes. The printed constructs are found to be nonimmunogenic in vitro and in vivo. Furthermore, delving into an innovative method for fabricating a vascularized myocardial tissue‐on‐a‐chip, the silk‐based ink is used as supporting hydrogel for encapsulating human induced pluripotent stem cell derived cardiac spheroids (hiPSC‐CSs) and creating perfusable vascularized channels via an embedded bioprinting technique. The ability is confirmed of silk‐based supporting hydrogel toward maturation and viability of hiPSC‐CSs and endothelial cells, and for applications in evaluating drug toxicity.     

3D Bioprinting of Miniaturized Tissues Embedded in Self-Assembled Nanoparticle-Based Fibrillar Platforms

The creation of microphysiological systems like tissue and organ-on-chip for in vitro modeling of human physiology and diseases is gathering increasing interest. However, the platforms used to build these systems have limitations concerning implementation, automation, and cost-effectiveness. Moreover, their typical plastic-based housing materials are poor recreations of native tissue extracellular matrix (ECM) and barriers. Here, the controlled self-assembly of plant-derived cellulose nanocrystals (CNC) is combined with the concept of 3D bioprinting in suspension baths for the direct biofabrication of microphysiological systems embedded within an ECM mimetic fibrillar support material. The developed support CNC fluid gel allows exceptionally high-resolution bioprinting of 3D constructs with arbitrary geometries and low restrictions of bioink choice. The further induction of CNC self-assembly with biocompatible calcium ions results in a transparent biomimetic nanoscaled fibrillar matrix that allows hosting different compartmentalized cell types and perfusable channels, has tailored permeability for biomacromolecules diffusion and cellular crosstalk, and holds structural stability to support long-term in vitro cell maturation. In summary, this xeno-free nanoscale CNC fibrillar matrix allows the biofabrication of hierarchical living constructs, opening new opportunities not only for developing physiologically relevant 3D in vitro models but also for a wide range of applications in regenerative medicine.     

Elastomeric Fibrous Hybrid Scaffold Supports In Vitro and In Vivo Tissue Formation

Biomimetic materials with biomechanical properties resembling those of native tissues while providing an environment for cell growth and tissue formation, are vital for tissue engineering (TE). Mechanical anisotropy is an important property of native cardiovascular tissues and directly influences tissue function. This study reports fabrication of anisotropic cell‐seeded constructs while retaining control over the construct's architecture and distribution of cells. Newly synthesized poly‐4‐hydroxybutyrate (P4HB) is fabricated with a dry spinning technique to create anelastomeric fibrous scaffold that allows control of fiber diameter, porosity, and rate ofdegradation. To allow cell and tissue ingrowth, hybrid scaffolds with mesenchymalstem cells (MSCs) encapsulated in a photocrosslinkable hydrogel were developed. Culturing the cellularized scaffolds in a cyclic stretch/flexure bioreactor resulted in tissue formation and confirmed the scaffold's performance under mechanical stimulation. In vivo experiments showed that the hybrid scaffold is capable of withstanding physiological pressures when implanted as a patch in the pulmonary artery. Aligned tissue formation occurred on the scaffold luminal surface without macroscopic thrombus formation. This combination of a novel, anisotropic fibrous scaffold and a tunable native‐like hydrogel for cellular encapsulation promoted formation of 3D tissue and provides a biologically functional composite scaffold for soft‐tissue engineering applications.     

Rapid Biofabrication of Printable Dense Collagen Bioinks of Tunable Properties

Recent convergence of the 3D printing of tissue‐like bioinks and regenerative medicine offers promise in the high‐throughput engineering of in vitro tissue models and organoids for drug screening and discovery research, and of potentially implantable neo‐tissues with tailored structural, biological, and mechanical properties. However, the current printing approaches are not compatible with collagen, the native scaffolding material. Herein, a unique biofabrication approach that uses automated gel aspiration‐ejection (GAE) is reported to potentially overcome these challenges. Automated‐GAE generates highly defined, aligned, dense collagen gel bioinks of various geometries (i.e., cylindrical, quadrangular, and tubular), dimensions, as well as tunable microstructural and mechanical properties that modulate seeded cellular responses. By densifying initial naturally derived reconstituted collagen hydrogels incorporating cells, automated‐GAE generates mini‐tissue building blocks with tailored protein fibril density and alignment, as well as cell loading, density and orientation according to the intended use. Surprisingly, a simple mathematical relationship defining the bioink compaction factor is found to be highly effective in predicting the initial and temporal properties of the bioinks in culture. Therefore, automated‐GAE will potentially also enable a fourth dimension to biofabrication, where cell–cell communications and cell‐extracellular matrix interactions as a function of time in culture can be predicted and modeled.     

Aligned Carbon Nanotube–Based Flexible Gel Substrates for Engineering Biohybrid Tissue Actuators

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

Engineered 3D Silk‐Based Metastasis Models: Interactions Between Human Breast Adenocarcinoma,Mesenchymal Stem Cells and Osteoblast‐Like Cells

Bone metastasis occurs in 70% of breast cancer patients and is a frequent cause of morbidity in cancer patients. A delicate balance exists in the bone microenvironment, but the functional dynamics underlying the tumor cell‐microenvironment interactions remain poorly understood. 3D in vitro model systems of metastasis can throw new light on this phenomenon. Silk protein fibroin scaffolds, are cytocompatible for 3D cancer cell culture. They are structurally more resistant to protease degradation than other native biomaterials making these matrices suitable for cancer modeling. In this report, human breast adenocarcinoma cells, human osteoblast like cells and mesenchymal stem cells are co‐cultered. Cancer cells and osteoblast‐like cells are found to interact through secreted products. Decreased population of osteoblast‐like cells and mineralization of extracellular matrix are observed as a result of co‐culture. Significantly increased migration of breast cancer cells is observed in the bone‐like constructs than in non‐seeded scaffolds. The co‐culture constructs show significant increase in drug resistance, invasiveness and angiogenicity. Co‐culture of breast cancer cells with osteoblast like cells and mesenchymal stem cells also indicate that the interaction of cancer cells with bone microenvironment varies with spatial organization, presence of osteogenic factors as well as stromal cell type. Here, results show that 3D in vitro co‐culture models is possibly a better system to study and target cancer progression.     

Compact Physics-Based Circuit Models for Graphene Nanoribbon Interconnects

Physics-based equivalent circuit models are presented for armchair and zigzag graphene nanoribbons (GNRs), and their conductances have been benchmarked against those of carbon nanotubes and copper wires. Atomically thick GNRs with smooth edges can potentially have smaller resistances compared with copper wires with unity aspect ratios for widths below 8 nm and stacks of noninteracting GNRs can have substantially smaller resistivities compared to Cu wires. It is shown that rough edges can increase the resistance of narrow GNRs by an order of magnitude. This fact highlights the need for patterning methods that can produce relatively smooth edges to fabricate low resistance GNR interconnects.