Aligned Microchannels Research Articles

LDH nanoparticles-doped cellulose nanofiber scaffolds with aligned microchannels direct high-efficiency neural regeneration and organized neural circuit remodeling through RhoA/Rock/Myosin II pathway

Spinal cord injury (SCI) triggers interconnected malignant pathological cascades culminating in structural abnormalities and composition changes of neural tissues and impairs spinal cord tissue function. Cellulose nanofibers (CNF) have considerable potential in mimicking tissue microstructure for nerve regeneration, but the effectiveness of CNF in repairing SCI remains poorly understood. In this study, we designed a Mg–Fe layered double hydroxide (LDH)-doped cellulose nanofiber (CNF) scaffold with aligned intact microchannels and homogeneously distributed pores (CNF-LDH), loaded with retinoic acid and sonic hedgehog (CNF-LDH-RS) for neuroregeneration. The aligned microchannel structure and chemical cues in the scaffold were designed further to enhance the differentiation of neural stem cells towards neurons and promote axon growth while inhibiting differentiation to astrocytes. Transplanting the scaffolds into a completely transected SCI mice model dramatically improved behavioral and electrophysiological outcomes underpinned by robust neuronal regeneration, significant axonal growth and orderly neural circuit remodeling. RNA-seq analysis revealed the pivotal roles of the RhoA/Rock/Myosin II pathway and neuroactive ligand-receptor interaction pathway in SCI repair by CNF-LDH-RS. Particularly, Myosin II emerged as a key gene for functional recovery, and its effect on negative regulation of axon growth was suppressed by the scaffolds, resulting in a distinctly oriented growth of the axons along the microchannel structure. The results indicate that CNF-LDH scaffolds rationally combined with physical and biochemical cues create promising tissue-engineered substrates to facilitate the repair of spinal cord injury.

Decellularized Scaffolds with Double-Layer Aligned Microchannels Induce the Oriented Growth of Bladder Smooth Muscle Cells: toward Urethral and Ureteral Reconstruction.

There is a great clinical need for regenerating the urinary tissue. Native urethra and ureter have bidirectional aligned smooth muscle cells (SMCs) layers, which plays a pivotal role for micturition and transport the urine and inhibit reflux. Up to now, urinary scaffolds have not been designed to induce the native-mimicking aligned arrangement of SMCs. In this study, we engineered a tubular decellularized extracellular matrix (dECM) with an intact internal layer and bidirectional aligned microchannels in the tubular wall, which was realized by the subcutaneous implantation of a template, followed by the removal of the template, and decellularization. The dense and intact internal layer effectively increased the leakage pressure of the tubular dECM scaffolds. The rat-derived dECM scaffolds with three different sizes of microchannels were fabricated by tailoring the fiber diameter of the templates. The rat-derived dECM scaffolds exhibiting microchannels of ∼ 65μm showed suitable mechanical properties, good ability to induce the bidirectional alignment and growth of human bladder SMCs (HBdSMC) and elevated higher functional protein expression in vitro. These data indicated that rat-derived tubular dECM scaffolds manifesting double-layer aligned microchannel may be promising candidates to induce the native-mimicking regeneration of SMCs in urethra and ureter reconstruction. This article is protected by copyright. All rights reserved.

LDH-doped gelatin-chitosan scaffold with aligned microchannels improves anti-inflammation and neuronal regeneration with guided axonal growth for effectively recovering spinal cord injury

Spinal cord injury (SCI) causes immune cell infiltration, neuronal death and permanent motor dysfunction. Effective treatment for SCI requires simultaneous suppression of the inhibitory and inflammatory microenvironment and enhancement of the pro-regenerative potential at SCI sites. However, realizing neuronal regeneration with guided axon growth and anti-inflammation simultaneously is currently challenging. In this study, a layered double hydroxides (LDH)-doped gelatin-chitosan scaffold with aligned microchannels (GC-LDH/A scaffold) combined with chemical and structural repair effects was developed to regulate immune microenvironment and promote directional neurogenesis. The GC-LDH/A scaffold was prepared by anisotropic freezing of a mixture of Mg-Fe layered double hydroxides (Mg-Fe LDH), gelatin and chitosan. The LDH, gelatin and aligned microchannel structure work together to promote neuronal regeneration. Chitosan and the aligned microchannel structure have a function of anti-inflammation while the latter also guides axonal growth. The repair effect of this scaffold was assessed by restoring a completely transected spinal cord injury, and the results showed that the GC-LDH/A scaffold effectively activated the anti-inflammatory polarization of macrophages and microglia, promoted neurogenesis and guided axonal growth from the rostral to caudal of the lesion site. The key mediator of functional recovery in SCI is Myosin II, which negatively regulates axonal growth; however, the aligned microchannel structure inhibits its activity and reverses the repair effect. This study provides a promising strategy for addressing the repair challenges for effective SCI treatment.

High performance aqueous asymmetric supercapacitors developed by interfacial engineering wood-derived nanostructured electrodes

Supercapacitors (SCs) are becoming new candidates in the field of sustainable energy supply. Nevertheless, the unsatisfactory energy density due to the narrow voltage window of the supercapacitor is the main barrier to its practical application. Developing appropriate electrode materials to improve the electrochemical performance of SCs and broaden the operating voltage of supercapacitors are imperative. Herein, compatible interfacial engineering wood-derived nanostructured electrodes for aqueous asymmetric supercapacitors (AASCs) are demonstrated. The 3D carbonized wood matrix serves as a high specific surface area current collector and a porous host for the high capacitive active substance, which is composed of manganese dioxide (MnO2) nanowires and polyaniline (PANI) nanoparticles grown uniformly on the porous wall of aligned microchannels (CW@MnO2 and CW@PANI). The resulting electrochemical exchange reactive sites enable the positive electrode to deliver a high areal capacitance of 729 mF cm−2 at 1 mA cm−2 (369 F g−1 at 0.5 A g−1). The negative electrode delivers a high areal capacitance of 1721 mF cm−2 at 1 mA cm−2 (848 F g−1 at 0.5 A g−1). The areal capacitance of two electrodes is superior to most reported supercapacitor electrodes. Additionally, the assembled CW@MnO2//CW@PANI AASC achieves a desirable energy density (170.84 μWh cm−2 at a power density of 0.5 mW cm−2) because a considerable work function difference between electrodes achieved a 2 V wide voltage window. The results of this study provide a critical benchmark and optimistic incentives to adopt natural hierarchical structures to enhance the performance of new-generation energy-related systems.

Thermoelectric Freeze-Casting of Biopolymer Blends: Fabrication and Characterization of Large-Size Scaffolds for Nerve Tissue Engineering Applications.

Peripheral nerve injuries (PNIs) are detrimental to the quality of life of affected individuals. Patients are often left with life-long ailments that affect them physically and psychologically. Autologous nerve transplant is still the gold standard treatment for PNIs despite limited donor site and partial recovery of nerve functions. Nerve guidance conduits are used as a nerve graft substitute and are efficient for the repair of small nerve gaps but require further improvement for repairs exceeding 30 mm. Freeze-casting is an interesting fabrication method for the conception of scaffolds meant for nerve tissue engineering since the microstructure obtained comprises highly aligned micro-channels. The present work focuses on the fabrication and characterization of large scaffolds (35 mm length, 5 mm diameter) made of collagen/chitosan blends by freeze-casting via thermoelectric effect instead of traditional freezing solvents. As a freeze-casting microstructure reference, scaffolds made from pure collagen were used for comparison. Scaffolds were covalently crosslinked for better performance under load and laminins were further added to enhance cell interactions. Microstructural features of lamellar pores display an average aspect ratio of 0.67 ± 0.2 for all compositions. Longitudinally aligned micro-channels are reported as well as enhanced mechanical properties in traction under physiological-like conditions (37 °C, pH = 7.4) resulting from crosslinking treatment. Cell viability assays using a rat Schwann cell line derived from sciatic nerve (S16) indicate that scaffold cytocompatibility is similar between scaffolds made from collagen only and scaffolds made from collagen/chitosan blend with high collagen content. These results confirm that freeze-casting via thermoelectric effect is a reliable manufacturing strategy for the fabrication of biopolymer scaffolds for future peripheral nerve repair applications.

Nanostructured membranes with interconnected pores via a combination of phase inversion and solvent crystallisation approach

Polyethersulfone (PES) is an important membrane material in wastewater and medical applications due to its outstanding thermal and mechanical properties. However, when processing the PES into the asymmetric membranes through nonsolvent-induced phase separation (NIPS) method, the emergence of macro voids and discrete porosities has hampered its permeation performance. In this study, we present a novel phase inversion and solvent crystallisation approach that combines NIPS with the combined crystallisation and diffusion (CCD) technique, named as (NIPS-CCD) to significantly improve PES ultrafiltration membrane permeation without use of any additives. The NIPS-CCD method is simple and requires only a change in casting plate material and water bath temperature. The resultant membrane features a typical NIPS-like skin layer and elongated finger like structure, which are integrally connected to aligned microchannels formed through the CCD technique. With the enhanced pore connectivity, a 50-fold increase in water permeation up to 771 LMH bar−1 was obtained from the NIPS-CCD membrane with the pore size of 6–7 nm. This approach can be easily adapted to industrial production for other high-performance membrane materials with a minimal process modification, making it a promising strategy for improving the permeation properties of membranes used in various applications.

Self-snapping hydrogel-based electroactive microchannels as nerve guidance conduits.

Peripheral nerve regeneration with large defects needs innovative design of nerve guidance conduits (NGCs) which possess anisotropic guidance, electrical induction and right mechanical properties in one. Herein, we present, for the first time, facile fabrication and efficient neural differentiation guidance of anisotropic, conductive, self-snapping, hydrogel-based NGCs. The hydrogels were fabricated via crosslinking of graphitic carbon nitride (g-C3N4) upon exposure with blue light, incorporated with graphene oxide (GO). Incorporation of GO and in situ reduction greatly enhanced surface charges, while decayed light penetration endowed the hydrogel with an intriguing self-snapping feature by the virtue of a crosslinking gradient. The hydrogels were in the optimal mechanical stiffness range for peripheral nerve regeneration and supported normal viability and proliferation of neural cells. The PC12 ​cells differentiated on the electroactive g-C3N4 H/rGO3 (3 ​mg/mL GO loading) hydrogel presented 47% longer neurite length than that of the pristine g-C3N4 H hydrogel. Furthermore, the NGC with aligned microchannels was successfully fabricated using sacrificial melt electrowriting (MEW) moulding, the anisotropic microchannels of the 10 ​μm width showed optimal neurite guidance. Such anisotropic, electroactive, self-snapping NGCs may possess great potential for repairing peripheral nerve injuries.

Graphitic carbon layer-encapsulated Co nanoparticles embedded on porous carbonized wood as a self-supported chainmail oxygen electrode for rechargeable Zn-air batteries

A self-supported chainmail electrocatalyst is developed by embedding graphitic carbon layer-encapsulated Co nanoparticles on N-doped carbonized wood (Co@NCW) as an advanced air cathode for rechargeable Zn-air batteries (ZABs). The NCW with open aligned microchannels facilitates O2 and electrolyte permeation and transportation, while the uniformly distributed graphitic carbon layer-encapsulated Co nanoparticles on NCW featuring fast electron transfer kinetics provide abundant triphase reaction sites for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). The Co@NCW exhibits a half-wave potential of 0.89 V vs. reversible hydrogen electrode (RHE) for ORR outperforming the Pt/C (0.85 V vs. RHE) and an overpotential of 410 mV for the OER (10 mA cm−2) comparable to RuO2 (340 mV). A rechargeable ZAB assembled with Co@NCW presents a power density of 47.5 mW cm−2 and excellent stability at 5 mA cm−2 for 240 h. This work provides an effective strategy to fabricate a practically applicable oxygen electrode for ZABs.

Bubble freeze casting artificial rattan

Although bioinspired technology is expected to play an important role in the discovery of prospective advanced materials, facile synthesis of large-scale bioinspired structural materials remains a major challenge. Here we introduce a new all-in-one design methodology, bubble freeze casting, a universally applicable strategy to assemble building units via the simultaneous growth of aligned bubbles and ordered ice crystals, for fabricating biomimetic structural materials with multiscale long-range aligned microchannels. Through in-situ microscopy, we captured the nucleation-growth process of bubbles during bubble freeze casting, and revealed the formation mechanism and controllable factors of the bubble. This work takes an important step toward realistic rattan-like multiscale aligned microchannel structures and may have a broad implication in design of future biomimetic multiscale structural materials. We expect this methodology to be used to assemble a wide variety of building units (e.g., polymers, ceramic powders, various nanoparticles) for fabricating versatile multiscale aligned porous materials, which are in demand for a range of applications, such as ultrafast liquid absorption, microfluidics, electrodes and solar-driven steam generation.

Integrated solar seawater desalination and power generation via plasmonic sawdust-derived biochar: Waste to wealth

Solar steam generation (SSG) provides a promising technique to remedy the worldwide water and energy crisis with minimum environmental impact. Herein, we successfully recycled the wood wastes (sawdust) to construct biochar as an evaporator via the pyrolysis technique which was performed at low temperature to keep the abundant aligned microchannels across the wood structure, increasing water transportation to the surface. Bimetallic plasmonic nanoshells dopped the biochar to enhance SG via the multiple nucleation sites, benefiting from their excellent light absorption. Besides, a thermoelectric (TE) generator can be integrated with the Ag-Cu/ SDB@PVA membrane for concurrent steam and electricity generation. As a result, the evaporator achieves a simultaneous evaporation rate of 1.49 kg m−2 h−1 (90.4% efficiency) and a power density of 34.7 mW/m2 under 1 sun illumination. The highest potential and power density of induced electricity can be achieved under blue LED illumination. Thanks to the different interactions of salt ions with the functional groups of biochar, our evaporator shows extraordinarily salt-resistant performance under 1 sun illumination. Based on its excellent energy-conversion efficiency, facile and cost-effective fabrication process, salt-resistance, and durability, our evaporator may be a promising generator for drinkable water and electricity on a large scale.

Anisotropic, biomorphic cellular Si3N4 ceramics with directional well-aligned nanowhisker arrays based on wood-mimetic architectures

Inspired by the transport behavior of water and ions through the aligned channels in trees, we demonstrate a facile, scalable approach for constructing biomorphic cellular Si3N4 ceramic frameworks with well-aligned nanowhisker arrays on the surface of directionally aligned microchannel alignments. Through a facile Y(NO3)3 solution infiltration into wood-derived carbon preforms and subsequent heat treatment, we can faultlessly duplicate the anisotropic wood architectures into free-standing bulk porous Si3N4 ceramics. Firstly, α-Si3N4 microchannels were synthesized on the surface of CB-templates via carbothermal reduction nitridation (CRN). And then, homogeneous distributed Y−Si−O−N liquid phase on the walls of microchannel facilitated the anisotropic β-Si3N4 grain growth to form nanowhisker arrays. The dense aligned microchannels with low-tortuosity enable excellent load carrying capacity and thermal conduction through the entire materials. As a result, the porous Si3N4 ceramics exhibited an outstanding thermal conductivity (TC, kR ≈ 6.26 W·m−1·K−1), a superior flexural strength (σL ≈ 29.4 MPa), and a relative high anisotropic ratio of TC (kR/kL = 4.1). The orientation dependence of the microstructure-property relations may offer a promising perspective for the fabrication of multifunctional ceramics.

Ultrahigh-Capacity and Scalable Architected Battery Electrodes via Tortuosity Modulation.

A thick electrode with high areal capacity is a straightforward approach to maximize the energy density of batteries, but the development of thick electrodes suffers from both fabrication challenges and electron/ion transport limitations. In this work, a low-tortuosity LiFePO4 (LFP) electrode with ultrahigh loadings of active materials and a highly efficient transport network was constructed by a facile and scalable templated phase inversion method. The instant solidification of polymers during phase inversion enables the fabrication of ultrathick yet robust electrodes. The open and aligned microchannels with interconnected porous walls provide direct and short ion transport pathways, while the encapsulation of active materials in the carbon framework offers a continuous pathway for electron transport. Benefiting from the structural advantages, the ultrathick bilayer LiFePO4 electrodes (up to 1.2 mm) demonstrate marked improvements in rate performance and cycling stability under high areal loadings (up to 100 mg cm-2). Simulation and operando structural characterization also reveal fast transport kinetics. Combined with the scalable fabrication, our proposed strategy presents an effective alternative for designing practical high energy/power density electrodes at low cost.

Patterned vascularization in a directional ice-templated scaffold of decellularized matrix.

Vascularization is fundamental for large‐scale tissue engineering. Most of the current vascularization strategies including microfluidics and three‐dimensional (3D) printing aim to precisely fabricate microchannels for individual microvessels. However, few studies have examined the remodeling capacity of the microvessels in the engineered constructs, which is important for transplantation in vivo. Here we present a method for patterning microvessels in a directional ice‐templated scaffold of decellularized porcine kidney extracellular matrix. The aligned microchannels made by directional ice templating allowed for fast and efficient cell seeding. The pure decellularized matrix without any fixatives or cross‐linkers maximized the potential of tissue remodeling. Dramatical microvascular remodeling happened in the scaffold in 2 weeks, from small primary microvessel segments to long patterned microvessels. The majority of the microvessels were aligned in parallel and interconnected with each other to form a network. This method is compatible with other engineering techniques, such as microfluidics and 3D printing, and multiple cell types can be co‐cultured to make complex vascularized tissue and organ models.

Co3O4-based catalysts derived from natural wood with hierarchical structure for elemental mercury oxidation

Wood vessel in natural wood (NW) as the channel for water and inorganic salt transport has a natural aligned microchannel structure and a great hydrophily. In the present work, NW was used as catalyst support which was directly impregnated in Co(NO3)2 solution and then calcined in N2 atmosphere to prepare a catalyst (denoted as Co/NWBC-OS), which was called a one-step calcination method. For comparison, NW biochar (NWBC) derived from pyrolytic NW was also impregnated in Co(NO3)2 solution and calcined in N2 atmosphere to prepare catalyst (denoted as Co/NWBC-TS), which was called a two-step calcination method. Characterization results reveal that NW possesses a greater hydrophily and wettability than NWBC, which is beneficial to impregnation process resulting in a better active components dispersion. In the meanwhile, Co/NWBC-OS has a higher Co3+/Co2+ ratio and more surface chemisorbed oxygen. The higher Co3+/Co2+ ratio can generate more oxygen vacancies which can capture and activate gaseous oxygen to form more surface chemisorbed oxygen. Surface chemisorbed oxygen as the main active site can greatly promote Hg0 removal performance. These results lead to an excellent Hg0 removal efficiency of Co/NWBC-OS which is 99% at 180 °C. Additionally, O2 and NO can promote the Hg0 removal process whereas H2O, SO2 and NH3 exert an obviously prohibited effect on Hg0 removal performance.

Poplar branch bio-template synthesis of mesoporous hollow Co3O4 hierarchical architecture as an anode for long-life lithium ion batteries

Mesoporous hollow hierarchical structures play an important role in enhancing the lithium storage performances of Co3O4 anode materials. In this work, Co3O4 with mesoporous hollow structure has been successfully fabricated by simple impregnation and subsequently air calcination using poplar branch as bio-template. The product calcined at 600 °C (PB-Co600) perfectly duplicates the 3D aligned microchannels structure of poplar branch. Importantly, the wall of aligned microchannels in PB-Co600 is constructed by a lot of irregular cross-linked Co3O4 nanoparticles and there are abundant mesopores on the surface. As an anode, it exhibits high reversible capacity and remarkable long-cycle stability. At 0.1 A g-1, it can deliver a high specific capacity of 1153.7 mA h g-1 after 100 cycles, and even at 1 A g-1, the reversible specific capacity of 555.7 mA h g-1 can be retained after cycling 1000 times. The excellent lithium storage performance of PB-Co600 may be attributed to its unique hierarchical structure, which is not only favorable to the rapid transfer of substances and Li+ ion diffusion, but also alleviates the volume change during the charge/discharge cycle. Furthermore, the existence of oxygen vacancies and pseudo-capacitance also contributes significantly to the superior lithium storage performance of the PB-Co600 electrode. Therefore, the PB-Co600 prepared by a large-scale and eco-friendly route can be used as a potential candidate anode for LIBs.

A natural polymer-based porous sponge with capillary-mimicking microchannels for rapid hemostasis

Natural polymer materials have attracted great attention in the field of hemostasis because of their wide range of source, nontoxicity, hydrophilicity, and air permeability. In the present study, two natural polymers composed of carboxymethyl chitosan (CMCS) and sodium carboxymethylcellulose (CMCNa) plus γ-(2,3-epoxypropoxy) propytrimethoxysilane (KH560) that serves as a crosslinking agent were selected to synthesize a capillary-mimicking composite hemostatic (CCK) sponge with a low density, interconnected microchannel architecture, suitable mechanical strength, high resilience, and ultrastrong liquid absorption capacity. The introduction of a large number of hydrophilic carboxymethyl functional groups and the design of capillary-mimicking structures formed by the ice segregation-induced self-assembly (ISISA) process endowed the CCK sponges with an ultrastrong liquid absorption capacity, which significantly enhanced the hemostatic ability of the materials. Both in vivo and in vitro hemostatic experiments confirmed the potential of the CCK sponges to achieve rapid hemostasis. Additionally, cytotoxicity and hemolysis assays showed that the CCK sponges exhibited good biocompatibility and hemocompatibility. The possible hemostatic mechanism was also discussed in this study. In conclusion, the capillary-mimicking hemostatic sponge exhibits a high potential to induce rapid hemostasis in prehospital emergency and clinical settings. STATEMENT OF SIGNIFICANCE: In the present study, an oriented composite hemostatic (CCK) sponge with a capillary-mimicking structure formed by the ice segregation-induced self-assembly (ISISA) process was designed and used to achieve rapid hemostasis. The unique aligned microchannel structure of the sponge exhibited an ultrastrong capillary-mimicking action and endowed the prepared CCK hemostatic sponge with a strong liquid absorption capacity. By changing the proportion of raw materials, we could modify the unique capillary-mimicking structure with aligned microchannels. Two natural polymer-based materials with abundant hydrophilic groups were chosen to prepare the CCK sponge to fully utilize the characteristics of this structure. The oriented natural polymer-based porous sponge with capillary-mimicking microchannels exhibited a strong hemostatic ability in both in vivo and in vitro tests. The results showed that the CCK sponge with the capillary-mimicking structure has a high potential to achieve rapid hemostasis.

Redox active coating on graphite surface of hierarchically porous wood electrodes for supercapacitor application

A free-standing electrode with hierarchical pores and graphite surface is derived from wood pellet via a catalytic graphitization. The aligned microchannels of natural wood and the high conductivity of graphite has enabled fast ionic and electronic transport. The high porosity leads to a large surface area for the deposition of redox active materials. After an electrodeposition of Ni(OH)2 and Co(OH)2 on the graphitized wood, the electrode exhibits a high areal capacity without significant degradation in the electrochemical performance. An asymmetric supercapacitor, with a graphitized wood as the negative electrode and a Ni(OH)2/Co(OH)2 deposited wood as the positive electrode, shows a high areal capacitance of 2 409 m F/cm2, a high energy density of 0.75 mWh/cm2 at a power density of 0.750 mW/cm2. This high performance, free-standing and biodegradable wood-derived asymmetric supercapacitor demonstrates promising applications as energy storage devices.

A controllable oil-triggered actuator with aligned microchannel design for implementing precise deformation.

Soft actuators with the integration of facile preparation, rapid actuation rate, sophisticated motions, and precise control over deformation for application in complex devices are still highly desirable. Inspired by the aligned structures of moisture responsive pineal scales, an oil-triggered Janus actuator composed of a smooth hydrophobic surface and a superhydrophobic surface with aligned microchannels by simple laser etching was fabricated successfully, which can deform into various desirable shapes and recover to the original shape when triggered by oil and ethanol molecules. The aligned microchannel design causes different oil spread distances in the longitudinal and transverse directions, resulting in orientation-controlled bending and twisting with large-scale displacement. By changing the orientations of the patterned microchannels, one-dimensional folding deformation, twisting, rolling curling and object-inspired architectures can be facilely programmed. The reversible oil-triggered actuator will inspire more attractive applications such as in vivo surgery, biomimetic devices, energy harvesting systems and soft robotics.

Subcutaneously engineered autologous extracellular matrix scaffolds with aligned microchannels for enhanced tendon regeneration: Aligned microchannel scaffolds for tendon repair

Improved strategies for the treatment of tendon defects are required to successfully restore mechanical function and strength to the damaged tissue. This remains a scientific and clinical challenge, given the tendon's limited innate regenerative capacity. Here, we present an engineering solution that stimulates the host cell's remodeling abilities. We combined precision-designed templates with subcutaneous implantation to generate decellularized autologous extracellular matrix (aECM) scaffolds that had highly aligned microchannels after removal of templates and cellular components. The aECM scaffolds promoted rapid cell infiltration, favorable macrophage responses, collagen-rich extracellular matrix (ECM) synthesis, and physiological tissue remodeling in rat Achilles tendon defects. At three months post-surgery, the mechanical strength of tenocyte-populated ‘neo-tendons' was comparable to pre-injury state tendons. Overall, we demonstrated an in vivo bioengineering strategy for improved restoration of tendon tissue, which also offers wider implications for the regeneration of other highly organized tissues.

Aligned microchannel polymer-nanotube composites for peripheral nerve regeneration: Small molecule drug delivery

Peripheral nerve injury accounts for roughly 2.8% of all trauma patients with an annual cost of 7 billion USD in the U.S. alone. Current treatment options rely on surgical intervention with the use of an autograft, despite associated shortcomings. Engineered nerve guidance conduits, stem cell therapies, and transient electrical stimulation have reported to increase speeds of functional recovery. As an alternative to the conduction effects of electrical stimulation, we have designed and optimized a nerve guidance conduit with aligned microchannels for the sustained release of a small molecule drug that promotes nerve impulse conduction. A biodegradable chitosan structure reinforced with drug-loaded halloysite nanotubes (HNT) was formed into a foam-like conduit with interconnected, longitudinally-aligned pores with an average pore size of 59.3 ± 14.2 μm. The aligned composite with HNTs produced anisotropic mechanical behavior with a Young's modulus of 0.33 ± 0.1 MPa, very similar to that of native peripheral nerve. This manuscript reports on the sustained delivery of 4-Aminopyridine (4AP, molecular weight 94.1146 g/mol), a potassium-channel blocker as a growth factor alternative to enhance the rate of nerve regeneration. The conduit formulation released a total of 30 ± 2% of the encapsulated 4AP in the first 7 days. Human Schwann cells showed elevated expression of key proteins such as nerve growth factor, myelin protein zero, and brain derived neurotrophic factor in a 4AP dose dependent manner. Preliminary in vivo studies in a critical-sized sciatic nerve defect in Wistar rats confirmed conduit suturability and strength to withstand ambulatory forces over 4 weeks of their implantation. Histological evaluations suggest conduit biocompatibility and Schwann cell infiltration and organization within the conduit and lumen. These nerve guidance conduits and 4AP sustained delivery may serve as an attractive strategy for nerve repair and regeneration.