ABSTRACT
Flexible electronic/optoelectronic systems that can intimately integrate onto the surfaces of vital organ systems have the potential to offer revolutionary diagnostic and therapeutic capabilities relevant to a wide spectrum of diseases and disorders. The critical interfaces between such technologies and living tissues must provide soft mechanical coupling and efficient optical/electrical/chemical exchange. Here, we introduce a functional adhesive bioelectronic-tissue interface material, in the forms of mechanically compliant, electrically conductive, and optically transparent encapsulating coatings, interfacial layers or supporting matrices. These materials strongly bond both to the surfaces of the devices and to those of different internal organs, with stable adhesion for several days to months, in chemistries that can be tailored to bioresorb at controlled rates. Experimental demonstrations in live animal models include device applications that range from battery-free optoelectronic systems for deep-brain optogenetics and subdermal phototherapy to wireless millimetre-scale pacemakers and flexible multielectrode epicardial arrays. These advances have immediate applicability across nearly all types of bioelectronic/optoelectronic system currently used in animal model studies, and they also have the potential for future treatment of life-threatening diseases and disorders in humans.
Subject(s)
Absorbable Implants , Adhesives , Animals , Electric Conductivity , ElectronicsABSTRACT
BACKGROUND: Long non-coding RNAs (lncRNAs) have been certified to play vital biological functions in glioma and have received considerable attention in the recent literature. Nonetheless, the role of LINC01158 in glioma remains to be elucidated. METHODS: qRT-PCR, western blot and GEPIA database were applied for reporting the expression of CENPK and LINC01158 in glioma and the correlation between LINC01158 and CENPK expression. EdU, colony formation, CCK-8, caspase-3 activity and TUNEL assays probed the impacts of LINC01158 on glioma cell growth. Subcellular fractionation and FISH assays revealed the cellular distribution of LINC01158. Luciferase reporter and RIP assays examined ceRNA network of LINC01158, CENPK and miR-6734-3p. RESULTS: LINC01158 and CENPK were both overexpressed in glioma and a positive regulation of LINC01158 on CENPK was corroborated. LINC01158 served a pro-proliferative and anti-apoptotic part in glioma by sponging miR-6734-3p to augment CENPK. CONCLUSION: LINC01158 enhances CENPK by serving as sponge for miR-6734-3p to facilitate glioma development, proposing LINC01158 as a new player in glioma.
ABSTRACT
Spinal cord injuries (SCI) normally disrupt the long axonal tracts of the spinal cord and cause permanent neurological deficits, for which there is currently a lack of effective therapeutic methods. Biomaterial-based regenerative medicine is a pivotal strategy to induce axonal regeneration through delivery of biophysical and/or biochemical regulatory cues by biomaterials. We previously fabricated a hierarchically aligned fibrin hydrogel (AFG) that could promote neurogenic differentiation of stem cells in vitro and has been successfully applied for peripheral nerve and spinal cord regeneration in rats. In this study, AFG was used to repair a canine lumbar segment 2 hemisection spinal cord injury, and the consistency of histological, imageological and behavioral results was compared. AFG was used to construct an aligned fiber bridge that supported cell adhesion in vitro and rapidly facilitated tissue invasion along the long axis of fibers in vivo, Moreover, in vivo results demonstrated regrowth of axons in an oriented pattern connecting the rostral and caudal stumps. Consistent results were confirmed by diffusion tensor imaging, which allowed successful tracing of reconnected nerve fibers across the defect. As a result, directional axonal regrowth contributed to significantly improved recovery of motor functional behavior of SCI canines with AFG implantation. Our results suggest that AFG has great promise for rapidly directing axonal regrowth for nerve regeneration.
Subject(s)
Fibrin , Hydrogels , Nanofibers , Spinal Cord Injuries/veterinary , Spinal Cord Regeneration/physiology , Animals , Biocompatible Materials , Biomechanical Phenomena , Cell Proliferation , Dogs , Human Umbilical Vein Endothelial Cells , Humans , Spinal Cord Injuries/therapy , Tissue ScaffoldsABSTRACT
Titanium (Ti) with nanoscale structure on the surface exhibits excellent biocompatibility and bone integration. Once implanted, the surgical implantation may lead to bacterial infection and inflammatory reaction, which cause the implant failure. In this work, irregular and nanorod-shaped ZnO nanoparticles were doped into TiO2 nanotubes (TNTs) with inner diameter of about 50 nm by electro-deposition. The antibacterial properties of ZnO incorporated into TiO2 nanotubes (TNTs/ZnO) were evaluated using Staphylococcus aureus (S. aureus). Zn ions released from the nanoparticles and the morphology could work together, improving antibacterial effectiveness up to 99.3% compared with the TNTs. Macrophages were cultured on the samples to determine their respective anti-inflammatory properties. The proliferation and viability of macrophages were evaluated by the CCK-8 method and Live&Dead stain, and the morphology of the cells was observed by scanning electron microscopy. Results indicated that TNTs/ZnO has a significant inhibitory effect on the proliferation and adhesion of macrophages, which could be used to prevent chronic inflammation and control the inflammatory reaction. Besides, the release of Zn ions from the ZnO nanoparticles is a long-term process, which could be beneficial for bone integration. Results demonstrate that ZnO deposited into TNTs improved the antibacterial effectiveness and weakened the inflammatory reaction of titanium-based implants, which is a promising approach to enhance their bioactivity.
ABSTRACT
Rehabilitation and regenerative medicine are two promising approaches for spinal cord injury (SCI) recovery, but their combination has been limited. Conductive biomaterials could bridge regenerative scaffolds with electrical stimulation by inducing axon regeneration and supporting physiological electrical signal transmission. Here, we developed aligned conductive hydrogel fibers by incorporating carbon nanotubes (CNTs) into methacrylate acylated gelatin (GelMA) hydrogel via rotating liquid bath electrospinning. The electrospun CNT/GelMA hydrogel fibers mimicked the micro-scale aligned structure, conductivity, and soft mechanical properties of neural axons. For in vitro studies, CNT/GelMA hydrogel fibers supported PC12 cell proliferation and aligned adhesion, which was enhanced by electrical stimulation (ES). Similarly, the combination of aligned CNT/GelMA hydrogel fibers and ES promoted neuronal differentiation and axon-like neurite sprouting in neural stem cells (NSCs). Furthermore, CNT/GelMA hydrogel fibers were transplanted into a T9 transection rat spinal cord injury model for in vivo studies. The results showed that the incorporating CNTs could remain at the injury site with the GelMA fibers biodegraded and improve the conductivity of regenerative tissue. The aligned structure of the hydrogel could induce the neural fibers regeneration, and the ES enhanced the remyelination and axonal regeneration. Behavioral assessments and electrophysiological results suggest that the combination of aligned CNT/GelMA hydrogel fibers and ES could significantly restore motor function in rats. This study demonstrates that conductive aligned CNT/GelMA hydrogel fibers can not only induce neural regeneration as a scaffold but also support ESto promote spinal cord injury recovery. The conductive hydrogel fibers enable merging regenerative medicine and rehabilitation, showing great potential for satisfactory locomotor recovery after SCI.
ABSTRACT
Soft electronics provide effective means for continuous monitoring of a diverse set of biophysical and biochemical signals from the human body. However, the sensitivities, functions, spatial distributions, and many other features of such sensors remain fixed after deployment and cannot be adjusted on demand. Here, laser-induced porous graphene is exploited as the sensing material, and dope it with permanent magnetic particles to create hard magnetic graphene nanocomposite (HMGN) that can self-assemble onto a flexible carrying substrate through magnetic force, in a reversible and reconfigurable manner. A set of soft electronics in HMGN exhibits enhanced performances in the measurements of electrophysiological signals, temperature, and concentrations of metabolites. All these flexible HMGN sensors can adhere to a carrying substrate at any position and in any spatial arrangement, to allow for wearable sensing with customizable sensitivity, modality, and spatial coverage. The HMGN represents a promising material for constructing soft electronics that can be reconfigured for various applications.
ABSTRACT
Additively manufactured (AM) biodegradable zinc (Zn) alloys have recently emerged as promising porous bone-substituting materials, due to their moderate degradation rates, good biocompatibility, geometrically ordered microarchitectures, and bone-mimicking mechanical properties. While AM Zn alloy porous scaffolds mimicking the mechanical properties of trabecular bone have been previously reported, mimicking the mechanical properties of cortical bone remains a formidable challenge. To overcome this challenge, we developed the AM Zn-3Mg alloy. We used laser powder bed fusion to process Zn-3Mg and compared it with pure Zn. The AM Zn-3Mg alloy exhibited significantly refined grains and a unique microstructure with interlaced α-Zn/Mg2Zn11 phases. The compressive properties of the solid Zn-3Mg specimens greatly exceeded their tensile properties, with a compressive yield strength of up to 601 MPa and an ultimate strain of >60 %. We then designed and fabricated functionally graded porous structures with a solid core and achieved cortical bone-mimicking mechanical properties, including a compressive yield strength of >120 MPa and an elastic modulus of ≈20 GPa. The biodegradation rates of the Zn-3Mg specimens were lower than those of pure Zn and could be adjusted by tuning the AM process parameters. The Zn-3Mg specimens also exhibited improved biocompatibility as compared to pure Zn, including higher metabolic activity and enhanced osteogenic behavior of MC3T3 cells cultured with the extracts from the Zn-3Mg alloy specimens. Altogether, these results marked major progress in developing AM porous biodegradable metallic bone substitutes, which paved the way toward clinical adoption of Zn-based scaffolds for the treatment of load-bearing bony defects. STATEMENT OF SIGNIFICANCE: Our study presents a significant advancement in the realm of biodegradable metallic bone substitutes through the development of an additively manufactured Zn-3Mg alloy. This novel alloy showcases refined grains and a distinctive microstructure, enabling the fabrication of functionally graded porous structures with mechanical properties resembling cortical bone. The achieved compressive yield strength and elastic modulus signify a critical leap toward mimicking the mechanical behavior of load-bearing bone. Moreover, our findings reveal tunable biodegradation rates and enhanced biocompatibility compared to pure Zn, emphasizing the potential clinical utility of Zn-based scaffolds for treating load-bearing bony defects. This breakthrough opens doors for the wider adoption of zinc-based materials in regenerative orthopedics.
Subject(s)
Alloys , Cortical Bone , Zinc , Alloys/chemistry , Alloys/pharmacology , Zinc/chemistry , Zinc/pharmacology , Animals , Mice , Cortical Bone/drug effects , Porosity , Magnesium/chemistry , Magnesium/pharmacology , Materials Testing , Compressive Strength , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Absorbable Implants , Elastic Modulus , Cell LineABSTRACT
Implantable sensors can directly interface with various organs for precise evaluation of health status. However, extracting signals from such sensors mainly requires transcutaneous wires, integrated circuit chips, or cumbersome readout equipment, which increases the risks of infection, reduces biocompatibility, or limits portability. Here, we develop a set of millimeter-scale, chip-less, and battery-less magnetic implants paired with a fully integrated wearable device for measuring biophysical and biochemical signals. The wearable device can induce a large amplitude damped vibration of the magnetic implants and capture their subsequent motions wirelessly. These motions reflect the biophysical conditions surrounding the implants and the concentration of a specific biochemical depending on the surface modification. Experiments in rat models demonstrate the capabilities of measuring cerebrospinal fluid (CSF) viscosity, intracranial pressure, and CSF glucose levels. This miniaturized system opens the possibility for continuous, wireless monitoring of a wide range of biophysical and biochemical conditions within the living organism.
Subject(s)
Wearable Electronic Devices , Wireless Technology , Animals , Rats , Prostheses and Implants , Physical Phenomena , Magnetic PhenomenaABSTRACT
Bio/ecoresorbable electronic systems create unique opportunities in implantable medical devices that serve a need over a finite time period and then disappear naturally to eliminate the need for extraction surgeries. A critical challenge in the development of this type of technology is in materials that can serve as thin, stable barriers to surrounding ground water or biofluids, yet ultimately dissolve completely to benign end products. This paper describes a class of inorganic material (silicon oxynitride, SiON) that can be formed in thin films by plasma-enhanced chemical vapor deposition for this purpose. In vitro studies suggest that SiON and its dissolution products are biocompatible, indicating the potential for its use in implantable devices. A facile process to fabricate flexible, wafer-scale multilayer films bypasses limitations associated with the mechanical fragility of inorganic thin films. Systematic computational, analytical, and experimental studies highlight the essential materials aspects. Demonstrations in wireless light-emitting diodes both in vitro and in vivo illustrate the practical use of these materials strategies. The ability to select degradation rates and water permeability through fine tuning of chemical compositions and thicknesses provides the opportunity to obtain a range of functional lifetimes to meet different application requirements.
Subject(s)
Absorbable Implants , Electronics , Water/chemistryABSTRACT
Nanofibers exist ubiquitously in natural extracellular matrix (ECM) of all kinds of human tissues forming hydrated interwoven network. Electrospinning nanotechnology has been proven to be a powerful technique to fabricate controllable nanofibers mimicking the natural ECM structures. Hyaluronic acid (HA), as a critical component of natural ECM, has been widely used in tissue engineering and regenerative medicine. In this study, pure HA nanofibers with average diameter of 33 +/- 5 nm, 59 +/- 12 nm, 79 +/- 12 nm and 113 +/- 19 nm were successfully prepared using different electrospinning parameters. The effect of the ambient relative humidity on HA electrospinnability was investigated for the first time in detail, which was proven to be one of the most important factors to control the morphology of HA nanofibers beside the solution properties. A critical value of humidity for a defined HA solution was observed, only below which HA nanofibers with similar diameters and morphologies could be successfully obtained. When the ambient relative humidity was higher than the critical value, the HA nanofibers started dissolving at the cross points and even fused together forming a spreading layer. Moreover, only a small amount of N, N-Dimethylformamide (DMF) was found to be required to promote the electrospinnability of HA solution by mixing with water as solvents. With the increase in the DMF content, the surface tension of the solution decreased significantly, which was thought to be benefit for the stable Taylor cone and fluid jet formation in electrospinning. At the same time, it should be noted that the conductivity of the solution also decreased with the increase of DMF content in the solution, which was believed to be responsible for the increasing diameters of HA nanofibers corresponding to higher DMF content. Controllable HA nanofibers with diameter below 100 nm have great promising for developing novel nanobiomaterials applied in tissue engineering and regenerative medicine.
Subject(s)
Electrochemistry/methods , Hyaluronic Acid/chemistry , Nanostructures/chemistry , Nanostructures/ultrastructure , Solvents/chemistry , Humidity , Macromolecular Substances/chemistry , Materials Testing , Molecular Conformation , Particle Size , Rotation , Surface PropertiesABSTRACT
Cellular microstructures form naturally in many living organisms (e.g., flowers and leaves) to provide vital functions in synthesis, transport of nutrients, and regulation of growth. Although heterogeneous cellular microstructures are believed to play pivotal roles in their three-dimensional (3D) shape formation, programming 3D curved mesosurfaces with cellular designs remains elusive in man-made systems. We report a rational microlattice design that allows transformation of 2D films into programmable 3D curved mesosurfaces through mechanically guided assembly. Analytical modeling and a machine learning-based computational approach serve as the basis for shape programming and determine the heterogeneous 2D microlattice patterns required for target 3D curved surfaces. About 30 geometries are presented, including both regular and biological mesosurfaces. Demonstrations include a conformable cardiac electronic device, a stingray-like dual mode actuator, and a 3D electronic cell scaffold.
ABSTRACT
Nerve guidance conduits with hollow lumen fail to regenerate critical-sized peripheral nerve defects (15 mm in rats and 25 mm in humans), which can be improved by a beneficial intraluminal microenvironment. However, individual cues provided by intraluminal filling materials are inadequate to eliminate the functional gap between regenerated nerves and normal nerves. Herein, an aligned fibrin/functionalized self-assembling peptide (AFG/fSAP) interpenetrating nanofiber hydrogel that exerting synergistic topographical and biochemical cues for peripheral nerve regeneration is constructed via electrospinning and molecular self-assembly. The hydrogel possesses an aligned structure, high water content, appropriate mechanical properties and suitable biodegradation capabilities for nerve repair, which enhances the alignment and neurotrophin secretion of primary Schwann cells (SCs) in vitro, and successfully bridges a 15-mm sciatic nerve gap in rats in vivo. The rats transplanted with the AFG/fSAP hydrogel exhibit satisfactory morphological and functional recovery in myelinated nerve fibers and innervated muscles. The motor function recovery facilitated by the AFG/fSAP hydrogel is comparable with that of autografts. Moreover, the AFG/fSAP hydrogel upregulates the regeneration-associated gene expression and activates the PI3K/Akt and MAPK signaling pathways in the regenerated nerve. Altogether, the AFG/fSAP hydrogel represents a promising approach for peripheral nerve repair through an integration of structural guidance and biochemical stimulation.
ABSTRACT
3D, hierarchical micro/nanostructures formed with advanced functional materials are of growing interest due to their broad potential utility in electronics, robotics, battery technology, and biomedical engineering. Among various strategies in 3D micro/nanofabrication, a set of methods based on compressive buckling offers wide-ranging material compatibility, fabrication scalability, and precise process control. Previously reports on this type of approach rely on a single, planar prestretched elastomeric platform to transform thin-film precursors with 2D layouts into 3D architectures. The simple planar configuration of bonding sites between these precursors and their assembly substrates prevents the realization of certain types of complex 3D geometries. In this paper, a set of hierarchical assembly concepts is reported that leverage multiple layers of prestretched elastomeric substrates to induce not only compressive buckling of 2D precursors bonded to them but also of themselves, thereby creating 3D mesostructures mounted at multiple levels of 3D frameworks with complex, elaborate configurations. Control over strains used in these processes provides reversible access to multiple different 3D layouts in a given structure. Examples to demonstrate these ideas through both experimental and computational results span vertically aligned helices to closed 3D cages, selected for their relevance to 3D conformal bio-interfaces and multifunctional microsystems.
ABSTRACT
A hierarchically aligned fibrin hydrogel (AFG) that possesses soft stiffness and aligned nanofiber structure has been successfully proven to facilitate neuroregeneration in vitro and in vivo. However, its potential in promoting nerve regeneration in large animal models that is critical for clinical translation has not been sufficiently specified. Here, the effects of AFG on directing neuroregeneration in canine hemisected T12 spinal cord injuries were explored. Histologically obvious white matter regeneration consisting of a large area of consecutive, compact and aligned nerve fibers is induced by AFG, leading to a significant motor functional restoration. The canines with AFG implantation start to stand well with their defective legs from 3 to 4 weeks postoperatively and even effortlessly climb the steps from 7 to 8 weeks. Moreover, high-resolution multi-shot diffusion tensor imaging illustrates the spatiotemporal dynamics of nerve regeneration rapidly crossing the lesion within 4 weeks in the AFG group. Our findings indicate that AFG could be a potential therapeutic vehicle for spinal cord injury by inducing rapid white matter regeneration and restoring locomotion, pointing out its promising prospect in clinic practice.
ABSTRACT
Robots with submillimeter dimensions are of interest for applications that range from tools for minimally invasive surgical procedures in clinical medicine to vehicles for manipulating cells/tissues in biology research. The limited classes of structures and materials that can be used in such robots, however, create challenges in achieving desired performance parameters and modes of operation. Here, we introduce approaches in manufacturing and actuation that address these constraints to enable untethered, terrestrial robots with complex, three-dimensional (3D) geometries and heterogeneous material construction. The manufacturing procedure exploits controlled mechanical buckling to create 3D multimaterial structures in layouts that range from arrays of filaments and origami constructs to biomimetic configurations and others. A balance of forces associated with a one-way shape memory alloy and the elastic resilience of an encapsulating shell provides the basis for reversible deformations of these structures. Modes of locomotion and manipulation span from bending, twisting, and expansion upon global heating to linear/curvilinear crawling, walking, turning, and jumping upon laser-induced local thermal actuation. Photonic structures such as retroreflectors and colorimetric sensing materials support simple forms of wireless monitoring and localization. These collective advances in materials, manufacturing, actuation, and sensing add to a growing body of capabilities in this emerging field of technology.
Subject(s)
Robotics , Smart Materials , Biomimetics , Locomotion , WalkingABSTRACT
Extensive tissue engineering studies have supported the enhanced spinal cord regeneration by implantable scaffolds loaded with bioactive cues. However, scaffolds with single-cue delivery showed unsatisfactory effects, most likely due to the complex nature of hostile niches in the lesion area. In this regard, strategies of multi-modal delivery of multiple heterogeneous cell-regulatory cues are unmet needs for enhancing spinal cord repair, which requires a thorough understanding of the regenerative niche associated with spinal cord injury. Here, by combining hierarchically aligned fibrin hydrogel (AFG) and functionalized self-assembling peptides (fSAP), a novel multifunctional nanofiber composite hydrogel AFG/fSAP characterized with interpenetrating network is designed. Serving as a source of both biophysical and biochemical cues, AFG/fSAP can facilitate spinal cord regeneration via guiding regenerated tissues, accelerating axonal regrowth and remyelination, and promoting angiogenesis. Giving the synergistic effect of multiple cues, AFG/fSAP implantation contributes to anatomical, electrophysiological, and motor functional restorations in rats with spinal cord hemisection. This study provides a novel multi-modal approach for regeneration in central nervous system, which has potentials for clinical practice of spinal cord injury.
Subject(s)
Nanofibers , Spinal Cord Injuries , Spinal Cord Regeneration , Animals , Cues , Hydrogels , Nerve Regeneration , Rats , Spinal Cord , Spinal Cord Injuries/therapy , Tissue ScaffoldsABSTRACT
Liquid crystal elastomers (LCEs) are a class of soft active materials of increasing interest, because of their excellent actuation and optical performances. While LCEs show biomimetic mechanical properties (e.g., elastic modulus and strength) that can be matched with those of soft biological tissues, their biointegrated applications have been rarely explored, in part, due to their high actuation temperatures (typically above 60 °C) and low biaxial actuation performances (e.g., actuation strain typically below 10%). Here, unique mechanics-guided designs and fabrication schemes of LCE metamaterials are developed that allow access to unprecedented biaxial actuation strain (-53%) and biaxial coefficient of thermal expansion (-33 125 ppm K-1 ), significantly surpassing those (e.g., -20% and -5950 ppm K-1 ) reported previously. A low-temperature synthesis method with use of optimized composition ratios enables LCE metamaterials to offer reasonably high actuation stresses/strains at a substantially reduced actuation temperature (46 °C). Such biocompatible LCE metamaterials are integrated with medical dressing to develop a breathable, shrinkable, hemostatic patch as a means of noninvasive treatment. In vivo animal experiments of skin repair with both round and cross-shaped wounds demonstrate advantages of the hemostatic patch over conventional strategies (e.g., medical dressing and suturing) in accelerating skin regeneration, while avoiding scar and keloid generation.
Subject(s)
Biocompatible Materials/chemistry , Elastomers/chemistry , Liquid Crystals/chemistry , Regeneration , Skin/pathology , Animals , Bandages , Biocompatible Materials/pharmacology , Cell Line , Cell Survival/drug effects , Male , Rats , Rats, Sprague-Dawley , Regeneration/drug effects , TemperatureABSTRACT
Minimally invasive methods for temperature sensing and thermal modulation in living tissues have extensive applications in biological research and clinical care. As alternatives to bioelectronic devices for this purpose, functional nanomaterials that self-assemble into optically active microstructures offer important features in remote sensing, injectability, and compact size. This paper introduces a transient, or bioresorbable, system based on injectable slurries of well-defined microparticles that serve as photopumped lasers with temperature-sensitive emission wavelengths (>4-300 nm °C-1). The resulting platforms can act as tissue-embedded thermal sensors and, simultaneously, as distributed vehicles for thermal modulation. Each particle consists of a spherical resonator formed by self-organized cholesteric liquid crystal molecules doped with fluorophores as gain media, encapsulated in thin shells of soft hydrogels that offer adjustable rates of bioresorption through chemical modification. Detailed studies highlight fundamental aspects of these systems including particle sensitivity, lasing threshold, and size. Additional experiments explore functionality as photothermal agents with active temperature feedback (ΔT = 1 °C) and potential routes in remote evaluation of thermal transport properties. Cytotoxicity evaluations support their biocompatibility, and ex vivo demonstrations in Casper fish illustrate their ability to measure temperature within biological tissues with resolution of 0.01 °C. This collective set of results demonstrates a range of multifunctional capabilities in thermal sensing and modulation.
Subject(s)
Absorbable Implants , Liquid Crystals , Animals , Hydrogels , Lasers , TemperatureABSTRACT
Microfluidic technologies have wide-ranging applications in chemical analysis systems, drug delivery platforms, and artificial vascular networks. This latter area is particularly relevant to 3D cell cultures, engineered tissues, and artificial organs, where volumetric capabilities in fluid distribution are essential. Existing schemes for fabricating 3D microfluidic structures are constrained in realizing desired layout designs, producing physiologically relevant microvascular structures, and/or integrating active electronic/optoelectronic/microelectromechanical components for sensing and actuation. This paper presents a guided assembly approach that bypasses these limitations to yield complex 3D microvascular structures from 2D precursors that exploit the full sophistication of 2D fabrication methods. The capabilities extend to feature sizes <5 µm, in extended arrays and with various embedded sensors and actuators, across wide ranges of overall dimensions, in a parallel, high-throughput process. Examples include 3D microvascular networks with sophisticated layouts, deterministically designed and constructed to expand the geometries and operating features of artificial vascular networks.
ABSTRACT
The repair of infective bone defects is a great challenge in clinical work. It is of vital importance to develop a kind of bone scaffold with good osteogenic properties and long-term antibacterial activity for local anti-infection and bone regeneration. A porous mineralized collagen (MC) scaffold containing poly(d,l-lactide-co-glycolic acid) (PLGA) microspheres loaded with two antibacterial synthetic peptides, Pac-525 or KSL-W was developed and characterized via scanning electron microscopy (SEM), porosity measurement, swelling and mechanical tests. The results showed that the MC scaffold embedded with smooth and compact PLGA microspheres had a positive effect on cell growth and also had antibacterial properties. Through toxicity analysis, cell morphology and proliferation analysis and alkaline phosphatase evaluation, the antibacterial scaffolds showed excellent biocompatibility and osteogenic activity. The antibacterial property evaluated with Staphylococcus aureus and Escherichia coli suggested that the sustained release of Pac-525 or KSL-W from the scaffolds could inhibit the bacterial growth aforementioned in the long term. Our results suggest that the antimicrobial peptides-loaded MC bone scaffold has good antibacterial and osteogenic activities, thus providing a great promise for the treatment of infective bone defects.