Microstructured Biodegradable Fibers for Advanced Control Delivery

Biodegradable polymers are increasingly employed at the heart of therapeutic devices. Particularly in the form of thin and elongated fibers, they offer an effective strategy for controlled release in a variety of biomedical configurations such as sutures, scaffolds, wound dressings, surgical or imaging probes, and smart textiles. So far however, the fabrication of fiber‐based drug delivery systems has been unable to fulfill significant requirements of medicated fibers such as multifunctionality, adequate mechanical strength, drug loading capability, and complex release profiles of multiple substances. Here, a novel paradigm in the design and fabrication of microstructured biodegradable fibers with tailored mechanical properties and capable of predefined release patterns from multiple reservoirs is proposed. Different biodegradable polymers compatible with the scalable thermal drawing process are identified, and their release properties as thin films of various thicknesses in the fiber form are experimentally investigated and modeled. Multimaterial microstructured fibers with predictable complex release profiles of potentially different substances are then designed and fabricated. Moreover, the tunability of the mechanical properties via tailoring the drawing process parameters is demonstrated, as well as the ability to weave such fibers. This work establishes a novel platform for biodegradable microstructured fibers for applications in implants, sutures, wound dressing, or tissue scaffolds.     

Controlled Sub‐Micrometer Hierarchical Textures Engineered in Polymeric Fibers and Microchannels via Thermal Drawing

The controlled texturing of surfaces at the micro‐ and nanoscales is a powerful method for tailoring how materials interact with liquids, electromagnetic waves, or biological tissues. The increasing scientific and technological interest in advanced fibers and fabrics has triggered a strong motivation for leveraging the use of textures on fiber surfaces. Thus far however, fiber‐processing techniques have exhibited an inherent limitation due to the smoothing out of surface textures by polymer reflow, restricting achievable feature sizes. In this article, a theoretical framework is established from which a strategy is developed to reduce the surface tension of the textured polymer, thus drastically slowing down thermal reflow. With this approach the fabrication of potentially kilometers‐long polymer fibers with controlled hierarchical surface textures of unprecedented complexity and with feature sizes down to a few hundreds of nanometers is demonstrated, two orders of magnitude below current configurations. Using such fibers as molds, 3D microchannels are also fabricated with textured inner surfaces within soft polymers such as poly(dimethylsiloxane), at dimensions and a degree of simplicity impossible to reach with current techniques. This strategy for the texturing of high curvature surfaces opens novel opportunities in bioengineering, regenerative scaffolds, microfluidics, and smart textiles.     

Highly Stretchable Conducting SIBS‐P3HT Fibers

Poly(styrene‐β‐isobutylene‐β‐styrene)‐poly(3‐hexylthiophene) (SIBS‐P3HT) conducting composite fibers are successfully produced using a continuous flow approach. Composite fibers are stiffer than SIBS fibers and able to withstand strains of up 975% before breaking. These composite fibers exhibit interesting reversible mechanical and electrical characteristics, which are applied to demonstrate their strain gauging capabilities. This will facilitate their potential applications in strain sensing or elastic electrodes. Here, the fabrication and characterization of highly stretchable electrically conducting SIBS‐P3HT fibers using a solvent/non‐solvent wet‐spinning technique is reported. This fabrication method combines the processability of conducting SIBS‐P3HT blends with wet‐spinning, resulting in fibers that could be easily spun up to several meters long. The resulting composite fiber materials exhibit an increased stiffness (higher Young’s modulus) but lower ductility compared to SIBS fibers. The fibers’ reversible mechanical and electrical characteristics are applied to demonstrate their strain gauging capabilities.     

Chinese‐Noodle‐Inspired Muscle Myofiber Fabrication

Much effort has been made to engineer artificial fiber‐shaped cellular constructs that can be potentially used as muscle fibers or blood vessels. However, existing microfiber‐based approaches for culturing cells are still limited to 2D systems, compatible with a restricted number of polymers (e.g., alginate) and always lacking in situ mechanical stimulation. Here, a simple, facile, and high‐throughput technique is reported to fabricate 3D cell‐laden hydrogel microfibers (named hydrogel noodles), inspired by the fabrication approach for Chinese Hele noodle. A magnetically actuated and noncontact method to apply tensile stretch on hydrogel noodles has also been developed. With this method, it is found that cellular strain‐threshold and saturation behaviors in hydrogel noodles differ substantially from their 2D analogs, including proliferation, spreading, and alignment. Moreover, it is shown that these cell‐laden microfibers can induce muscle myofiber formation by tensile stretching alone. This easily adaptable platform holds great potential for the creation of functional tissue constructs and probing mechanobiology in three dimensions.     

微结构光纤及其双折射特性的研究

主要对微结构光纤以及其双折射特性研究情况进行总结,首先介绍了微结构光纤的研究历程和基本概念,然后重点总结了微结构光纤的解析和数值分析方法,接着介绍了高双折射微结构光纤设计和最新研究进展,最后对微结构光纤的应用和研究前景进行了展望。     

Bioinspired Hydrogel Electrospun Fibers for Spinal Cord Regeneration

Fully simulating the components and microstructures of soft tissue is a challenge for its functional regeneration. A new aligned hydrogel microfiber scaffold for spinal cord regeneration is constructed with photocrosslinked gelatin methacryloyl (GelMA) and electrospinning technology. The directional porous hydrogel fibrous scaffold consistent with nerve axons is vital to guide cell migration and axon extension. The GelMA hydrogel electrospun fibers soak up water more than six times their weight, with a lower Young's modulus, providing a favorable survival and metabolic environment for neuronal cells. GelMA fibers further demonstrate higher antinestin, anti‐Tuj‐1, antisynaptophysin, and anti‐CD31 gene expression in neural stem cells, neuronal cells, synapses, and vascular endothelial cells, respectively. In contrast, anti‐GFAP and anti‐CS56 labeled astrocytes and glial scars of GelMA fibers are shown to be present in a lesser extent compared with gelatin fibers. The soft bionic scaffold constructed with electrospun GelMA hydrogel fibers not only facilitates the migration of neural stem cells and induces their differentiation into neuronal cells, but also inhibits the glial scar formation and promotes angiogenesis. Moreover, the scaffold with a high degree of elasticity can resist deformation without the protection of a bony spinal canal. The bioinspired aligned hydrogel microfiber proves to be efficient and versatile in triggering functional regeneration of the spinal cord.     

Fabrication of Thermoresponsive Hydrogel Scaffolds with Engineered Microscale Vasculatures

Precise fabrication of microscale vasculatures (MSVs) has long been an unresolved challenge in tissue engineering. Currently, light-assisted printing is the most common approach. However, this approach is often associated with an intricate fabrication process, high cost, and a requirement for specific photoresponsive materials. Here, thermoresponsive hydrogels are employed to induce volume shrinkage at 37 °C, which allows for MSV engineering without complex protocols. The thermoresponsive hydrogel consists of thermosensitive poly(N-isopropylacrylamide) and biocompatible gelatin methacrylate (GelMA). In cell culture, the thermoresponsive hydrogel exhibits an apparent volume shrinkage and effectively triggers the creation of MSVs with smaller size. The results show that a higher concentration of GelMA blocks the shrinkage, and the thermoresponsive hydrogel demonstrates different behaviors in water and air at 37 °C. The MSVs can be effectively fabricated using the sacrificial alginate fibers, and the minimum MSV diameter achieved is 50 µm. Human umbilical vein endothelial cells form endothelial monolayers in the MSVs. Osteosarcoma cells maintain high viability in the thermoresponsive hydrogel, and the in vivo experiment shows that the MSVs provide a site for the perfusion of host vessels. This technique may help in the development of a facile method for fabricating MSVs and demonstrates strong potential for clinical application in tissue regeneration.     

Scalable One‐Step Wet‐Spinning of Graphene Fibers and Yarns from Liquid Crystalline Dispersions of Graphene Oxide: Towards Multifunctional Textiles

Key points in the formation of liquid crystalline (LC) dispersions of graphene oxide (GO) and their processability via wet‐spinning to produce long lengths of micrometer‐dimensional fibers and yarns are addressed. Based on rheological and polarized optical microscopy investigations, a rational relation between GO sheet size and polydispersity, concentration, liquid crystallinity, and spinnability is proposed, leading to an understanding of lyotropic LC behavior and fiber spinnability. The knowledge gained from the straightforward formulation of LC GO “inks” in a range of processable concentrations enables the spinning of continuous conducting, strong, and robust fibers at concentrations as low as 0.075 wt%, eliminating the need for relatively concentrated spinning dope dispersions. The dilute LC GO dispersion is proven to be suitable for fiber spinning using a number of coagulation strategies, including non‐solvent precipitation, dispersion destabilization, ionic cross‐linking, and polyelectrolyte complexation. One‐step continuous spinning of graphene fibers and yarns is introduced for the first time by in situ spinning of LC GO in basic coagulation baths (i.e., NaOH or KOH), eliminating the need for post‐treatment processes. The thermal conductivity of these graphene fibers is found to be much higher than polycrystalline graphite and other types of 3D carbon based materials.     

Black‐Phosphorus‐Incorporated Hydrogel as a Conductive and Biodegradable Platform for Enhancement of the Neural Differentiation of Mesenchymal Stem Cells

Conductive hydrogel scaffolds have important applications for electroactive tissue repairs. However, the development of conductive hydrogel scaffolds tends to incorporate nonbiodegradable conductive nanomaterials that will remain in the human body as foreign matters. Herein, a biodegradable conductive hybrid hydrogel is demonstrated based on the integration of black phosphorus (BP) nanosheets into the hydrogel matrix. To address the challenge of applying BP nanosheets in tissue engineering due to its intrinsic instability, a polydopamine (PDA) modification method is developed to improve the stability. Moreover, PDA modification also enhances interfacial bonding between pristine BP nanosheets and the hydrogel matrix. The incorporation of polydopamine‐modified black phosphorous (BP@PDA) nanosheets into the gelatin methacryloyl (GelMA) hydrogels significantly enhances the electrical conductivity of the hydrogels and improves the cell migration of mesenchymal stem cells (MSCs) within the 3D scaffolds. On the basis of the gene expression and protein level assessments, the BP@PDA‐incorporated GelMA scaffold can significantly promote the differentiation of MSCs into neural‐like cells under the synergistic electrical stimulation. This strategy of integrating biodegradable conductive BP nanomaterials within a biocompatible hydrogel provides a new insight into the design of biomaterials for broad applications in tissue engineering of electroactive tissues, such as neural, cardiac, and skeletal muscle tissues.     

Wet‐Spun Biodegradable Fibers on Conducting Platforms: Novel Architectures for Muscle Regeneration

Novel biosynthetic platforms supporting ex vivo growth of partially differentiated muscle cells in an aligned linear orientation that is consistent with the structural requirements of muscle tissue are described. These platforms consist of biodegradable polymer fibers spatially aligned on a conducting polymer substrate. Long multinucleated myotubes are formed from differentiation of adherent myoblasts, which align longitudinally to the fiber axis to form linear cell‐seeded biosynthetic fiber constructs. The biodegradable polymer fibers bearing undifferentiated myoblasts can be detached from the substrate following culture. The ability to remove the muscle cell‐seeded polymer fibers when required provides the means to use the biodegradable fibers as linear muscle‐seeded scaffold components suitable for in vivo implantation into muscle. These fibers are shown to promote differentiation of muscle cells in a highly organized linear unbranched format in vitro and thereby potentially facilitate more stable integration into recipient tissue, providing structural support and mechanical protection for the donor cells. In addition, the conducting substrate on which the fibers are placed provides the potential to develop electrical stimulation paradigms for optimizing the ex vivo growth and synchronization of muscle cells on the biodegradable fibers prior to implantation into diseased or damaged muscle tissue.     

Self‐Assembled Hydrogel Fiber Bundles from Oppositely Charged Polyelectrolytes Mimic Micro‐/Nanoscale Hierarchy of Collagen

Fiber bundles are present in many tissues throughout the body. In most cases, collagen subunits spontaneously self‐assemble into a fibrilar structure that provides ductility to bone and constitutes the basis of muscle contraction. Translating these natural architectural features into a biomimetic scaffold still remains a great challenge. Here, a simple strategy is proposed to engineer biomimetic fiber bundles that replicate the self‐assembly and hierarchy of natural collagen fibers. The electrostatic interaction of methacrylated gellan gum with a countercharged chitosan polymer leads to the complexation of the polyelectrolytes. When directed through a polydimethylsiloxane channel, the polyelectrolytes form a hierarchical fibrous hydrogel demonstrating nanoscale periodic light/dark bands similar to D‐periodic bands in native collagen and align parallel fibrils at microscale. Importantly, collagen‐mimicking hydrogel fibers exhibit robust mechanical properties (MPa scale) at a single fiber bundle level and enable encapsulation of cells inside the fibers under cell‐friendly mild conditions. Presence of carboxyl‐ (in gellan gum) or amino‐ (in chitosan) functionalities further enables controlled peptide functionalization such as Arginylglycylaspartic acid (RGD) for biochemical mimicry (cell adhesion sites) of native collagen. This biomimetic‐aligned fibrous hydrogel system can potentially be used as a scaffold for tissue engineering as well as a drug/gene delivery vehicle.     

Recyclable Cytokines on Short and Injectable Polylactic Acid Fibers for Enhancing T‐Cell Function

The current practice of cytokine‐based immunotherapy relies on high doses and multiple injections of cytokine agents, which raises patients' inconvenience and economic burden. Here, sustainable and recyclable cytokine delivery based on short and injectable polymer fibers immobilized with interleukin (IL)‐2 and IL‐15 is demonstrated, which can be retained at the target tumor sites upon injection. In detail, electrospun polylactic acid (PLA) fibers are treated with aqueous ethanol solution for their dispersion, increasing the interfiber space for highly efficient biomolecule conjugation, and further immobilized with protein G via enzymatic dopamine coating. The protein G‐immobilized PLA fibers are cut into short fibers using a microtome, and filtering is performed to collect injectable short PLA (sPLA) fibers with the lengths of 15–100 µm. These sPLA fibers are further loaded with cytokines via the interaction between protein G and Fc, and cytokine‐loaded sPLA (Cyto‐sPLA) fibers are injected near the tumor sites using a syringe. The administration of Cyto‐sPLA fibers efficiently suppresses the tumor growth up to 70% by reinvigorating nonfunctional T cells to a functional state that can kill tumors in a sustainable and recyclable manner. The injectable sPLA‐fiber platform can be employed as a carrier for the efficient delivery of various agents in vivo.     

Ultrastretchable Helical Conductive Fibers Using Percolated Ag Nanoparticle Networks Encapsulated by Elastic Polymers with High Durability in Omnidirectional Deformations for Wearable Electronics

Stretchable interconnects with invariable conductivity and complete elasticity, which return to their original shape without morphological hysteresis, are attractive for the development of stretchable electronics. In this study, a polydimethylsiloxane‐coated multifilament polyurethane‐based helical conductive fiber is developed. The stretchable helical fibers exhibit remarkable electrical performance under stretching, negligible electrical and mechanical hysteresis, and high electrical reliability under repetitive deformation (10 000 cycles of stretching with 100% strain). The resistance of the helical fibers barely increases until the applied strain reaches the critical strain, which is based on the helical diameter of each fiber. According to finite element analysis, uniform stress distribution is maintained in the helical fibers even under full stretching, owing to the fibers' true helix structure. In addition, the stretchable helical fibers have the ability to completely return to their original shapes even after being fully compressed in the vertical direction. Cylinder‐shaped connecting pieces made using 3D printing are designed for stable connection between the helical fibers and commercial components. A deformable light‐emitting diode (LED) array and biaxially stretchable LED display are fabricated using helical fibers. A skin‐mountable band‐type oximeter with helical fiber‐based electrodes is also fabricated and used to demonstrate real‐time detection of cardiac activities and analysis of brain activities.     

Electrically Conductive Hydrogel Nerve Guidance Conduits for Peripheral Nerve Regeneration

Peripheral nerve injuries are serious conditions, and surgical treatment has critical limitations. Therefore, nerve guidance conduits (NGCs) are proposed as an alternative. In this study, multifunctional NGCs are fabricated for the regeneration of injured peripheral nerves. Graphene oxide (GO) and gelatin‐methacrylate (GelMA) are polymerized and chemically reduced to form reduced (GO/GelMA) (r(GO/GelMA)). The prepared materials present good electrical conductivity, flexibility, mechanical stability, and permeability, which are suitable for use as NGCs. In vitro studies show 2.1‐ and 1.4‐fold promotion of neuritogenesis of PC12 neuronal cells on r(GO/GelMA) compared to GelMA and unreduced GO/GelMA, respectively. Animal studies using a rat sciatic nerve injury model with a 10 mm gap between the proximal and distal regions of the defect reveal that r(GO/GelMA) NGCs significantly enhance peripheral nerve regeneration, indicated by improved muscle weight increase, electro‐conduction velocity, and sciatic nerve function index. Specifically, r(GO/GelMA) NGCs are utilized to potentiate regrowth with myelination in rat sciatic nerves followed by histological, immunohistological, and morphometrical analyses. This study successfully shows the feasibility of electrically conductive hydrogel NGCs as functional conduits for improved nerve regeneration in a preclinical study, where these NGCs can not only mimic nerve tissues but also strongly promote nerve regeneration.     

A Fundamental Study Into the Surface Functionalization of Soft Glass Microstructured Optical Fibers via Silane Coupling Agents

A method for the functionalization of surfaces within soft glass microstructured optical fibers has been developed, using self assembled monolayers (SAMs) of silane coupling agents. We demonstrate the use of measurements of the fiber capillary fill rate, as a positive test for a functionalized internal surface. A simple theoretical model is used for comparison with measured fill rates. During this work, adsorption kinetics for SAMs of octadecyltrichlororsilane onto lead silicate glass has been investigated. This work is a critically important first step for a plethora of applications in biophotonics, chemical fiber sensing as well offering promise for protecting fiber glass from degradation.     

Conformal Coating by High Pressure Chemical Deposition for Patterned Microwires of II–VI Semiconductors

Deposition techniques that can uniformly and conformally coat deep trenches and very high aspect ratio pores with uniform thickness films are valuable in the synthesis of complex three‐dimensionally structured materials. Here it is shown that high pressure chemical vapor deposition can be used to deposit conformal films of II–VI semiconductors such as ZnSe, ZnS, and ZnO into high aspect ratio pores. Microstructured optical fibers serve as tailored templates for the patterning of II–VI semiconductor microwire arrays of these materials with precision and flexibility. In this way, centimeters‐long microwires with exterior surfaces that conform well to the nearly atomically smooth silica templates can be fabricated by conformal coating. This process allows for II–VI semiconductors, which cannot be processed into optical fibers with conventional techniques, to be fabricated into step index and microstructured optical fibers.     

Gold Nanocomposite Bioink for Printing 3D Cardiac Constructs

Bioprinting is the most convenient microfabrication method to create biomimetic three‐dimensional (3D) cardiac tissue constructs, that 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, a gold nanorod (GNR)‐incorporated gelatin methacryloyl (GelMA)‐based bioink is developed for printing 3D functional cardiac tissue constructs. The GNR concentration is adjusted to create a proper microenvironment for the spreading and organization of cardiac cells. At optimized concentrations of GNR, the nanocomposite bioink has a low viscosity, similar to pristine inks, which allows for the easy integration of cells at high densities. As a result, rapid deposition of cell‐laden fibers at a high resolution is possible, while reducing shear stress on the encapsulated cells. In the printed GNR constructs, cardiac cells show improved cell adhesion and organization when compared to the constructs without GNRs. Furthermore, the incorporated GNRs bridge the electrically resistant pore walls of polymers, improve the cell‐to‐cell coupling, and promote synchronized contraction of the bioprinted constructs. Given its advantageous properties, this gold nanocomposite bioink may find wide application in cardiac tissue engineering.     

Wet‐Spun Stimuli‐Responsive Composite Fibers with Tunable Electrical Conductivity

Wet‐spun stimuli‐responsive composite fibers made of covalently crosslinked alginate with a high concentration of single‐walled carbon nanotubes (SWCNTs) are electroconductive and sensitive to humidity, pH, and ionic strength, due to pH‐tunable water absorbing properties of the covalently crosslinked alginate. The conductivity depends on the material swelling in humid atmosphere and aqueous solutions: the greater the swelling, the smaller is the electrical conductivity. The covalently crosslinked fibers reversibly deform during the swelling/shrinking. In the swollen state, the fibers are less conductive, while they return to the same level of conductivity after shrinking. This unique reversible change of electroconductivity of the SWCNT‐alginate fibers is due to the elastic deformation of the alginate network in the area of electrical contacts between SWCNT bundles arrested in the alginate matrix. Fibers of this kind can be used as a simple, robust, disposable, and biocompatible platform for electrotextiles, biosensors, and flexible electronics in biomedical and biotechnological applications.     

Nerve-Fiber-Inspired Construction of 3D Graphene “Tracks” Supported by Wood Fibers for Multifunctional Biocomposite with Metal-Level Thermal Conductivity

Given the rapid developments in modern electronics, there is an urgent need for polymer composites with excellent heat-dissipating capabilities to address the cooling problem of these devices. However, designing a highly thermally conductive polymer composite that can outperform metals and ceramics while also exhibiting high processability and low cost remains a challenge. Herein, inspired by the fibrous pathway of human nervous system, natural wood fibers (WFs) are used as the template and coated with graphene nanoplates (GNPs) via a simple electrostatic self-assembly approach. Subsequent hot-pressing process yields “core-sheath” microstructured fibers, wherein the GNPs are compactly contacted face to face and arranged along the surfaces of the fibrous WF “cores”. This WF@G biocomposite consists of highly efficient 3D fibrous “tracks” for heat transmission, resulting in an extremely high thermal conductivity of 134 W (m K)⁻¹, which is at par with those of many metals. It also exhibits several other desirable properties and functionalities, including high mechanical strength and excellent flame resistance as well as remarkable electromagnetic shielding and Joule heating performances, which has significant potential for use as a functional thermal management material (TMM). Hence, this study describes a simple yet scalable manufacturing technique for the development of advanced metal-level biomass-based TMMs.     

Fabrication and Electromechanical Characterization of a Piezoelectric Structural Fiber for Multifunctional Composites

The use of piezoceramic materials for structural sensing and actuation is a fairly well developed practice that has found use in a wide variety of applications. However, just as advanced composites offer numerous benefits over traditional engineering materials for structural design, actuators that utilize the active properties of piezoelectric fibers can improve upon many of the limitations encountered when using monolithic piezoceramic devices. Several new piezoelectric fiber composites have been developed; however, almost all studies have implemented these devices such that they are surface‐bonded patches used for sensing or actuation. This paper will introduce a novel active piezoelectric structural fiber that can be laid up in a composite material to perform sensing and actuation, in addition to providing load bearing functionality. The sensing and actuation aspects of this multifunctional material will allow composites to be designed with numerous embedded functions, including structural health monitoring, power generation, vibration sensing and control, damping, and shape control through anisotropic actuation. This effort has developed a set of manufacturing techniques to fabricate the multifunctional fiber using a SiC fiber core and a BaTiO₃ piezoelectric shell. The electromechanical coupling of the fiber is characterized using an atomic force microscope for various aspect ratios and is compared to predictions made using finite element modeling in ABAQUS. The results show good agreement between the finite element analysis model and indicate that the fibers could have coupling values as high as 68% of the active constituent used.