Aligned Poly Research Articles

Electrospun poly(ε-caprolactone)/poly(glycerol sebacate) aligned fibers fabricated with benign solvents for tendon tissue engineering.

The electrospinning technique is a commonly employed approach to fabricate fibers intended for various tissue engineering applications. The aim of this study is to develop a novel strategy for tendon repair through the use of aligned poly(ε-caprolactone) (PCL) and poly(glycerol sebacate) (PGS) fibers fabricated in benign solvents, and further explore the potential application of PGS in tendon tissue engineering (TTE). The fibers were characterized for their morphological and physicochemical properties; amniotic epithelial stem cells (AECs) were used to assess the fibers teno-inductive and immunomodulatory potential due to their ability to teno-differentiate undergoing first a stepwise epithelial to mesenchymal transition, and due to their documented therapeutic role in tendon regeneration. The addition of PGS to PCL improved the spinnability of the polymer solution, as well as the uniformity and directionality of the so-obtained fibers. The mechanical properties were in the range of most TTE applications, specifically in the case of PCL/PGS 4:1 and 2:1 ratios. Compared to PCL alone, the same ratios also allowed a better AECs infiltration and growth over 7 days of culture, and triggered the activation of tendon-related genes (SCX, COL1, TNMD) and the expression of tenomodulin (TNMD) at the protein level. Concerning the immunomodulatory properties, both PCL and PCL/PGS fibers negatively affected the immunomodulatory profile of AECs, up-regulating both anti-inflammatory (IL-10) and pro-inflammatory (IL-12) cytokines over 7 days of culture. Overall, PCL/PGS 2:1 fibers fabricated with benign solvents proved to be the most suitable composition for TTE application based on their topographical cues, mechanical properties, biocompatibility, and teno-inductive properties.

Design and fabrication of highly aligned poly(l‐lactide‐co‐ε‐caprolactone) nanofiber yarns and braided textiles

AbstractAn approach that combines a modified electrospinning method with thermal stretching post‐treatment is designed to fabricate poly(l‐lactide‐co‐ε‐caprolactone) (PLCL) electrospun nanofiber yarns (ENYs). The nanofiber diameter in the PLCL ENYs is found to present an increasing trend with the increasing of polymeric concentration. When the PLCL concentration reaches 13% (w/v), the as‐generated ENYs show bead‐free and uniform nanofibrous structure. Then, a thermally stretching technique is applied to process the primarily‐obtained PLCL ENYs. When the stretching temperature is set as 60 °C, the thermally‐stretched PLCL ENYs present superior fiber orientation and notably enhanced crystallinity, thus resulting in dramatically increased mechanical properties. Finally, the thermally stretched PLCL ENYs are further processed into braided fabrics, and their mechanical properties are found to possess an obviously increased trend with the increasing of ENY numbers, demonstrating the adjustment feasibility of the mechanical properties of ENY‐based textiles by controlling the ENY numbers. Importantly, the in vitro cell studies demonstrate that the ENY‐based braided textiles significantly support the adhesion and proliferation of human dermal fibroblasts (HDFs). In all, the present study provides an easily‐handling strategy to fabricate high performance PLCL ENYs, which shows promising future for the generation of advanced biomedical textiles.

Tendon Decellularized Matrix Modified Fibrous Scaffolds with Porous and Crimped Microstructure for Tendon Regeneration.

Current engineered synthetic scaffolds fail to functionally repair and regenerate ruptured native tendon tissues, partly because they cannot satisfy both the unique biological and biomechanical properties of these tissues. Ideal scaffolds for tendon repair and regeneration need to provide porous topographic structures and biological cues necessary for the efficient infiltration and tenogenic differentiation of embedded stem cells. To obtain crimped and porous scaffolds, highly aligned poly(l-lactide) fibers were prepared by electrospinning followed by postprocessing. Through a mild and controlled hydrogen gas foaming technique, we successfully transformed the crimped fibrous mats into three-dimensional porous scaffolds without sacrificing the crimped microstructure. Porcine derived decellularized tendon matrix was then grafted onto this porous scaffold through fiber surface modification and carbodiimide chemistry. These biofunctionalized, crimped, and porous scaffolds supported the proliferation, migration, and tenogenic induction of tendon derived stem/progenitor cells, while enabling adhesion to native tendons. Together, our data suggest that these biofunctionalized scaffolds can be exploited as promising engineered scaffolds for the treatment of acute tendon rupture.

Structure-Piezoelectric Property Relationships of Thin Films Composed of Electrospun Aligned Poly(vinylidene fluoride) Nanofibers.

In the past two decades, many studies on piezoelectric nanofibers (NFs) prepared from poly(vinylidene fluoride) (PVDF) and its copolymers, including single NFs, randomly oriented nonwoven mats, and aligned NFs, have been reported. However, studies on the relationships between the PVDF NF diameter, the orientation of the β-phase crystals inside NFs, and the piezoelectric properties of the NFs are still limited. In this study, the effect of the fiber diameter on the internal molecular packing/orientation and piezoelectric properties of aligned PVDF NF thin films was investigated. Herein, piezoelectric thin films composed of densely packed, uniaxially aligned, PVDF NFs with diameters ranging from 228 to 1315 nm were prepared by means of electrospinning with a rotating collector and successive hot-pressing and poling. The effect of the diameters of PVDF NFs on their internal structures, as well as the piezoelectric properties of the thin films, was investigated. All prepared NFs mainly contained β-phase crystals with a similar total crystallinity. The orientation of the β-phase crystals inside the NFs increased with an increase in the fiber diameter, resulting in an improved transverse piezoelectric coefficient (d31) for the thin films. The output voltage of the prepared thin films reached a maximum of 2.7 V at 104 Hz.

Anisotropically Conductive Hydrogels with Directionally Aligned PEDOT:PSS in a PVA Matrix.

Electrical anisotropy, which is characterized by the efficient transmission of electrical signals in specific directions, is prevalent in both natural and engineered systems. However, traditional anisotropically conductive materials are often rigid and dry, thus limiting their utility in applications aiming for the seamless integration of various technologies with biological tissues. In the present study, we introduce a method for precisely controlling the microstructures of conductive and insulating polymers to create highly anisotropically conductive composite hydrogels. Our methodology involves combining aligned poly(vinyl alcohol) microfibrils, infused poly(3,4-ethylenedioxythiophene) polystyrenesulfonate, and sodium citrate precipitation to form dense, aligned conductive paths. This significantly enhances the electrical conductivity anisotropy (σ∥/σ⊥ ≈ 60.8) within these composite hydrogels.

The effects of aligned poly(lactic-co-glycolic acid) nanofibrous mat containing gold nanoparticles after planting onto an injured spinal cord

Transplanted cells rarely survive because of the inflammatory cytokines after spinal cord injury. To increase the survival, we synthesized a hydrophilic and aligned nanofibrous mat. We electrospun thiolate (SH)/aligned (A) poly(lactic-co-glycolic acid) (PLGA) nanofibrous mats. The PLGA-SH (A) nanofibrous mats were conjugated with gold nanoparticles (GNPs) to increase the hydrophilicity. The contact angle is decreased from 105.3° ± 5.2 (for randomly directional PLGA mats) to 28.1° ± 2.8 (for PLGA-GNP (A) mats). Green fluorescent protein (GFP)-expressing neural progenitor cells (NPCs) were dissociated from the embryonic spinal cords of Fisher 344 rats. We embedded the embryonic spinal-cord-derived NPCs in glycol chitosan (gC)-oxidized hyaluronate (oHA) hydrogels (=NPC graft). The NPC graft was transplanted into spinal-cord-injured Sprague-Dawley rats. Afterwards, the aligned PLGA-GNP nanofibrous mat was positioned onto the NPC-grafted region (=Injury + NPC graft + PLGA-GNP (A) nanofibrous mat (INP) group). We also added Injury (=I) and Injury + NPC graft (=IN) groups as control groups. The survival outcomes of transplanted NPCs were noticeably increased in the INP group compared to those in the IN group. We suggest a separate implanting therapy of NPCs and a hydrophilic PLGA-GNP (A) nanofibrous mat for spinal cord injuries.

Surface Functional Modification by Ti3 C2 Tx MXene on PLLA Nanofibers for Optimizing Neural Stem Cell Engineering.

Optimizing cell substrates by surface modification of neural stem cells (NSCs), for efficient and oriented neurogenesis, represents a promising strategy for treating neurological diseases. However, developing substrates with the advanced surface functionality, conductivity, and biocompatibility required for practical application is still challenging. Here, Ti3 C2 Tx MXene is introduced as a coating nanomaterial for aligned poly(l-lactide) (PLLA) nanofibers (M-ANF) to enhance NSC neurogenesis and simultaneously tailor the cell growth direction. Ti3 C2 Tx MXene treatment provides a superior conductivity substrate with a surface rich in functional groups, hydrophilicity, and roughness, which can provide biochemical and physical cues to support NSC adhesion and proliferation. Moreover, Ti3 C2 Tx MXene coating significantly promotes NSC differentiation into both neurons and astrocytes. Interestingly, Ti3 C2 Tx MXene acts synergistically with the alignment of nanofibers to promote the growth of neurites, indicating enhanced maturation of these neurons. RNA sequencing analysis further reveals the molecular mechanism by which Ti3 C2 Tx MXene modulates the fate of NSCs. Notably, surface modification by Ti3 C2 Tx MXene mitigates the in vivo foreign body response to implanted PLLA nanofibers. This study confirms that Ti3 C2 Tx MXene provides multiple advantages for decorating the aligned PLLA nanofibers to cooperatively improve neural regeneration.

Dual-bioactive molecules loaded aligned core-shell microfibers for tendon tissue engineering

Development of a controlled delivery ultrafine fibrous system with two bioactive molecules is required to stimulate tendon healing in different phase. In this study, we used emulsion stable jet electrospinning to fabricate aligned poly(L-lactic acid) (PLLA) based ultrafine fibers with two small bioactive molecules of L-Arginine (Arg) and low molecular weight hyaluronic acid (HA). The results demonstrated that the aligned Arg/HA/PLLA microfibrous scaffold showed core-shell structure and allowed sequential release of Arg and HA due to their different electric charge. The scaffold also showed enhanced hydrophilicity, cell migration, spread and proliferation. Using an Achilles tendon repair model in rats, we demonstrated that this novel fibrous scaffold can prevent adhesion and promote tendon regeneration. Additionally, two p53 and ER-α-mediated signalling pathways were described as the probable main path of synergistic effects of the novel scaffold on tendon generation. Thus, this study may provide an important strategy for developing biofunctional and biomimetic tendon scaffolds.

Oriented fibrous poly (butylene adipate-co-terephthalate) matrices with nanotopographic features: Production and characterization

This is the first study to systematically investigate the effectiveness of electrospinning parameters and solvent properties on the random and aligned poly (butylene adipate-co-terephthalate) (PBAT) fiber surface nanotopography. Therefore, the combinations of three groups of solvents, good solvents, and a non-solvent, were used. While THF (tetrahydrofuran), HFIP (1,1,1,3,3,3-hexafluoro-2-propanol) and DCM (dichloromethane) were selected as good solvents, DMSO (dimethylsulfoxide) was chosen as a non-solvent. Four different phase separation mechanisms, non-solvent-induced phase separation (NIPS), vapor-induced phase separation (VIPS), breath figure (BF), and thermally induced phase separation (TIPS) mechanisms, were applied to create roughness on the fiber surfaces. Smooth, porous and groove surfaces with average fiber diameters in the range of about 800–2000 nm were obtained at different electrospinning conditions by these phase separation mechanisms. Porous random fibers with a few small pores were obtained by NIPS in the presence of THF/DMSO, while corrugated random fibers were produced by VIPS with DCM/HFIP. The groove roughness on the aligned THF/DMSO and aligned DCM/HFIP fibers was achieved by the TIPS mechanism thanks to the rapid evaporation rate of THF and HFIP. The most porous fibers were obtained in the presence of moisture with a good solvent mixture of DCM/HFIP. The results of this investigation show that the use of good and non-solvents together with moisture control affected not only the topography of fibrous matrices but also the bulk characteristics of PBAT nanofibrous matrices.

Massively Parallel Aligned Poly(vinylidene fluoride) Nanofibrils in All-Organic Dielectric Polymer Composite Films for Electric Energy Storage

It is a formidable challenge to combine the performance advantages of linear and nonlinear polymer dielectrics for developing all-organic film capacitors with high energy density and low loss. In this work, massively parallel aligned poly(vinylidene fluoride) (PVDF) nanofibrils were in situ fabricated for the first time in the polyethylene (PE) matrix via a multistage stretching technology involving hot stretching and solid-state stretching at an elevated temperature. The largely enhanced interfacial area of PVDF nanofibrils could effectively induce interfacial polarization, imparting PE composite films with a high dielectric constant of 4.50. More interestingly, the nanoconfinement effect of PVDF nanofibrils greatly restricted the migration of free electrons and impurity ions, and an impressive breakdown strength of 624 MV m–1 was obtained. As a result, the as-prepared PE/PVDF composite films exhibited an attractive discharged energy density of as high as 6.4 J cm–3, which was more than 10 times of the conventional counterparts, and outperformed the current linear dielectric polymers. The ingenious structure design of in situ nonlinear dielectric nanofibrils provides a promising approach to maximize the advantageous polarizations and minimize the disadvantageous polarizations in the linear and nonlinear polymer dielectric blends, achieving all-organic polymer dielectric composite films with high energy density and low loss.

Electrospun fiber-mediated delivery of neurotrophin-3 mRNA for neural tissue engineering applications.

Aligned electrospun fibers provide topographical cues and local therapeutic delivery to facilitate robust peripheral nerve regeneration. mRNA delivery enables transient expression of desired proteins that promote axonal regeneration. However, no prior work delivers mRNA from electrospun fibers for peripheral nerve regeneration applications. Here, we developed the first aligned electrospun fibers to deliver pseudouridine-modified (Ψ) neurotrophin-3 (NT-3) mRNA (ΨNT-3mRNA) to primary Schwann cells and assessed NT-3 secretion and bioactivity. We first electrospun aligned poly(L-lactic acid) (PLLA) fibers and coated them with the anionic substrates dextran sulfate sodium salt (DSS) or poly(3,4-dihydroxy-L-phenylalanine) (pDOPA). Cationic lipoplexes containing ΨNT-3mRNA complexed to JetMESSENGER® were then immobilized to the fibers, resulting in detectable ΨNT-3mRNA release for 28 days from all fiber groups investigated (PLLA+mRNA, 0.5DSS4h+mRNA, and 2pDOPA4h+mRNA). The 2pDOPA4h+mRNA group significantly increased Schwann cell secretion of NT-3 for 21 days compared to control PLLA fibers (p < 0.001-0.05) and, on average, increased Schwann cell secretion of NT-3 by ≥ 2-fold compared to bolus mRNA delivery from the 1µgBolus+mRNA and 3µgBolus+mRNA groups. The 2pDOPA4h+mRNA fibers supported Schwann cell secretion of NT-3 at levels that significantly increased dorsal root ganglia (DRG) neurite extension by 44% (p < 0.0001) and neurite area by 64% (p < 0.001) compared to control PLLA fibers. The data show that the 2pDOPA4h+mRNA fibers enhance the ability of Schwann cells to promote neurite growth from DRG, demonstrating this platform's potential capability to improve peripheral nerve regeneration. STATEMENT OF SIGNIFICANCE: Aligned electrospun fibers enhance axonal regeneration by providing structural support and guidance cues, but further therapeutic stimulation is necessary to improve functional outcomes. mRNA delivery enables the transient expression of therapeutic proteins, yet achieving local, sustained delivery remains challenging. Previous work shows that genetic material delivery from electrospun fibers improves regeneration; however, mRNA delivery has not been explored. Here, we examine mRNA delivery from aligned electrospun fibers to enhance neurite outgrowth. We show that immobilization of NT-3mRNA/JetMESSENGER® lipoplexes to aligned electrospun fibers functionalized with pDOPA enables local, sustained NT-3mRNA delivery to Schwann cells, increasing Schwann cell secretion of NT-3 and enhancing DRG neurite outgrowth. This study displays the potential benefits of electrospun fiber-mediated mRNA delivery platforms for neural tissue engineering.

A Strategy for Magnetic and Electric Stimulation to Enhance Proliferation and Differentiation of NPCs Seeded over PLA Electrospun Membranes

Neural progenitor cells (NPCs) have been shown to serve as an efficient therapeutic strategy in different cell therapy approaches, including spinal cord injury treatment. Despite the reported beneficial effects of NPC transplantation, the low survival and differentiation rates constrain important limitations. Herein, a new methodology has been developed to overcome both limitations by applying a combination of wireless electrical and magnetic stimulation to NPCs seeded on aligned poly(lactic acid) nanofibrous scaffolds for in vitro cell conditioning prior transplantation. Two stimulation patterns were tested and compared, continuous (long stimulus applied once a day) and intermittent (short stimulus applied three times a day). The results show that applied continuous stimulation promotes NPC proliferation and preferential differentiation into oligodendrocytic and neuronal lineages. A neural-like phenotypic induction was observed when compared to unstimulated NPCs. In contrast, intermittent stimulation patterns did not affect NPC proliferation and differentiation to oligodendrocytes or astrocytes morphology with a detrimental effect on neuronal differentiation. This study provides a new approach of using a combination of electric and magnetic stimulation to induce proliferation and further neuronal differentiation, which would improve therapy outcomes in disorders such as spinal cord injury.

Electrospun aligned poly(ε-caprolactone) nanofiber yarns guiding 3D organization of tendon stem/progenitor cells in tenogenic differentiation and tendon repair.

Hierarchical anisotropy structure directing 3D cellular orientation plays a crucial role in designing tendon tissue engineering scaffolds. Despite recent development of fabrication technologies for controlling cellular organization and design of scaffolds that mimic the anisotropic structure of native tendon tissue, improvement of tenogenic differentiation remains challenging. Herein, we present 3D aligned poly (ε-caprolactone) nanofiber yarns (NFYs) of varying diameter, fabricated using a dry-wet electrospinning approach, that integrate with nano- and micro-scale structure to mimic the hierarchical structure of collagen fascicles and fibers in native tendon tissue. These aligned NFYs exhibited good in vitro biocompatibility, and their ability to induce 3D cellular alignment and elongation of tendon stem/progenitor cells was demonstrated. Significantly, the aligned NFYs with a diameter of 50 μm were able to promote the tenogenic differentiation of tendon stem/progenitor cells due to the integration of aligned nanofibrous structure and suitable yarn diameter. Rat tendon repair results further showed that bundled NFYs encouraged tendon repair in vivo by inducing neo-collagen organization and orientation. These data suggest that electrospun bundled NFYs formed by aligned nanofibers can mimic the aligned hierarchical structure of native tendon tissue, highlighting their potential as a biomimetic multi-scale scaffold for tendon tissue regeneration.

Muscle degeneration in chronic massive rotator cuff tears of the shoulder: Addressing the real problem using a graphene matrix

Massive rotator cuff tears (MRCTs) of the shoulder cause disability and pain among the adult population. In chronic injuries, the tendon retraction and subsequently the loss of mechanical load lead to muscle atrophy, fat accumulation, and fibrosis formation over time. The intrinsic repair mechanism of muscle and the successful repair of the torn tendon cannot reverse the muscle degeneration following MRCTs. To address these limitations, we developed an electroconductive matrix by incorporating graphene nanoplatelets (GnPs) into aligned poly(l-lactic acid) (PLLA) nanofibers. This study aimed to understand 1) the effects of GnP matrices on muscle regeneration and inhibition of fat formation invitro and 2) the ability of GnP matrices to reverse muscle degenerative changes invivo following an MRCT. The GnP matrix significantly increased myotube formation, which can be attributed to enhanced intracellular calcium ions in myoblasts. Moreover, the GnP matrix suppressed adipogenesis in adipose-derived stem cells. These results supported the clinical effects of the GnP matrix on reducing fat accumulation and muscle atrophy. The histological evaluation showed the potential of the GnP matrix to reverse muscle atrophy, fat accumulation, and fibrosis in both supraspinatus and infraspinatus muscles at 24 and 32 wk after the chronic MRCTs of the rat shoulder. The pathological evaluation of internal organs confirmed the long-term biocompatibility of the GnP matrix. We found that reversing muscle degenerative changes improved the morphology and tensile properties of the tendon compared with current surgical techniques. The long-term biocompatibility and the ability of the GnP matrix to treat muscle degeneration are promising for the realization of MRCT healing and regeneration.

Properties of Electrospun Aligned Poly(lactic acid)/Collagen Fibers with Nanoporous Surface for Peripheral Nerve Tissue Engineering

AbstractIt is important for the functional recovery of defective nerves to construct a suitable microenvironment for nerve regeneration by optimizing the topological structure and biological functions of nerve grafts. Electrospun fibers are employed to mimic the extracellular matrix (ECM) and the effect of the porous features on fiber surface draws much attention. Yet, little is known about the effect of the nanotopology of the fiber surface in conjunction with collagen I (COL) on neural cells. Herein, poly(lactic acid) (PLA)/COL hybrid fibrous membranes with a nanoporous structure on a fiber surface are fabricated. The performance of the obtained fibrous membranes is investigated by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), water contact angle (WCA), and tensile test measurements. The cytotoxicity and biocompatibility of PLA/COL hybrid fibrous membranes and their effects on neural cells are systematically investigated. The physicochemical test results show that the PLA/COL hybrid fibrous membranes have appropriate mechanical properties and improved hydrophilicity. The MTT assay and hemolysis assay suggest the nontoxicity and good hemocompatibility of PLA/COL membranes. The nanoporous structure on the fiber surface and the introduction of COL synergistically promote proliferation and elongation of Schwann cells (SCs) and the extension of dorsal root ganglion (DRG) neurites.

Biomimetic Asymmetric Composite Dressing by Electrospinning with Aligned Nanofibrous and Micropatterned Structures for Severe Burn Wound Healing.

The surface structure and topography of biomaterials play a crucial role in directing cell behaviors and fates. Meanwhile, asymmetric dressings that mimic the natural skin structure have been identified as an effective strategy for enhancing wound healing. Inspired by the skin structure and the superhydrophobic structure of the lotus leaf, an asymmetric composite dressing was obtained by constructing an asymmetric structure and wettability surface modification on both sides of the sponge based on electrospinning. Among them, the collagen and quaternized chitosan sponge was fabricated by freeze-drying, followed by an aligned poly(ε-caprolactone) (PCL)/gelatin nanofiber hydrophilic inner layer and hierarchical micronanostructure PCL/polystyrene microsphere highly hydrophobic outer layer constructed on each side of the sponge. The proposed asymmetric composite dressing combines topological morphology with the material's properties to effectively prevent bacterial colonization/infection and promote wound healing by directing cellular behavior. In vitro experimental results confirmed that the aligned nanofiber inner layer effectively promotes cell adhesion, proliferation, directed cell growth, and migration. Meanwhile, the sponge has good water absorption and antibacterial properties, while the biomimetic hydrophobic outer layer exhibits strong mechanical properties and resistance to bacterial adhesion. In vivo results showed that the composite dressing can reduce inflammatory response, prevent infection, accelerate angiogenesis and epithelial regeneration, and significantly accelerate the healing of severe burns. Thus, the proposed bionic asymmetric dressing is expected to be a promising candidate for severe burn wound healing.

Influence of Touch-Spun Nanofiber Diameter on Contact Guidance during Peripheral Nerve Repair.

Peripheral nerve regeneration across large gaps remains clinically challenging and scaffold design plays a key role in nerve tissue engineering. One strategy to encourage regeneration has utilized nanofibers or conduits to exploit contact guidance within the neural regenerative milieu. Herein, we report the effect of nanofiber topography on two key aspects of regeneration: Schwann cell migration and neurite extension. Substrates possessing distinct diameter distributions (300 ± 40 to 900 ± 70 nm) of highly aligned poly(ε-caprolactone) nanofibers were fabricated by touch-spinning. Cell migratory behavior and contact guidance were then evaluated both at the tissue level using dorsal root ganglion tissue explants and the cellular level using dissociated Schwann cells. Explant studies showed that Schwann cells emigrated significantly farther on fibers than control. However, both Schwann cells and neurites emigrated from the tissue explants directionally along the fibers regardless of their diameter, and the data were characterized by high variation. At the cellular level, dissociated Schwann cells demonstrated biased migration in the direction of fiber alignment and exhibited a significantly higher biased velocity (0.2790 ± 0.0959 μm·min-1) on 900 ± 70 nm fibers compared to other nanofiber groups and similar to the velocity found during explant emigration on 900 nm fibers. Therefore, aligned, nanofibrous scaffolds of larger diameters (900 ± 70 nm) may be promising materials to enhance various aspects of nerve regeneration via contact guidance alone. While cells track along with the fibers, this contact guidance is bidirectional along the fiber, moving in the plane of alignment. Therefore, the next critical step to direct regeneration is to uncover haptotactic cues that enhance directed migration.

Enhanced Nerve Regeneration by Bionic Conductive Nerve Scaffold Under Electrical Stimulation.

Repair of peripheral nerve defect (PND) with a poor prognosis is hard to deal with. Neural conduit applied to nerve defect at present could not achieve the effect of autologous nerve transplantation. We prepared bionic conductive neural scaffolds to provide a new strategy for the treatment of PNDs. The highly aligned poly (L-lactic acid) (PLLA) fiber mats and the multi-microchannel conductive scaffolds were combined into bionic conductive nerve scaffolds, which were implanted into rats with sciatic nerve defects. The experimental animals were divided into the scaffold group (S), scaffold with electrical stimulation (ES) group (S&E), and autologous nerve transplantation group (AT). The regenerative effect of bionic conductive nerve scaffolds was analyzed. Compared with aligned PLLA fiber mats (APFMs), highly aligned fiber mats had a higher fiber orientation and did not change the tensile strength, Young’s modulus, degradation rate, elongation at break of the fiber membrane, and biocompatibility. The bionic conductive nerve scaffolds were well matched with the rat sciatic nerve. The evaluations of the sciatic nerve in Group S&E were close to those in Group AT and better than those in Group S. Immunohistochemical results showed that the expression levels of neurofilament heavy polypeptide (NF-H) and protein S100-B (S100-β) in Group S&E were higher than those in Group S, and the expression levels of low-density lipoprotein receptor-related protein 4 (LRP4), mitogen-activated protein kinase (MAPK) p38, extracellular signal-regulated kinase (ERK), and mitogen-activated protein kinase kinase (MEK) in Group AT were higher than those in Group S. Bionic conductive nerve scaffolds combined with ES could enhance peripheral nerve regeneration and achieve satisfactory nerve regeneration close to autologous nerve grafts. ERK, p38 MAPK, MEK, and LRP4 may be involved in peripheral nerve regeneration under ES.

Hyaluronic acid oligosaccharide-collagen mineralized product and aligned nanofibers with enhanced vascularization properties in bone tissue engineering

Considering the structural complexity of natural bone and the limitations of current treatment options, designing a biomimetic and functional tissue-engineered bone graft has been an urgent need for the replacement and regeneration of defected bone tissue. In light of the cell recruitment to the defect region, scaffold-guided bone tissue engineering has proven to be a viable strategy that is poised to deliver effective osseointegration and vascularization during bone remodeling. Herein, we provide an engineered bone scaffold based on aligned poly(lactic-co-glycolide) (PLGA) nanofibers incorporated with hyaluronic acid oligosaccharide-collagen mineralized microparticles (labeled oHA-Col/HAP) to guide the cell-specific orientation and osseointegration in bone healing. The aligned nanofibers were successfully prepared by a custom-made rotating mandrel with separating railings and HAs-Col/HAP mineralized microparticles were uniformly distributed in the composite scaffolds that acted as temporary templates for bone remodeling. The morphology, physicochemical properties and tensile strength of the scaffolds were characterized, the cell responses and in vivo biocompatibility and biodegradability of the scaffolds were also studied to evaluate the potential for bone tissue engineering. The experimental results illustrated that such anisotropic scaffolds loaded with oHA-Col/HAP microparticles mediated cell orderly arrangement conducive to the migration and recruitment of osseointegration-related cells and were stimulatory of cell proliferation. Those oHA-Col/HAP@PLGA scaffolds exhibited ideal biocompatibility and tissue regenerative capacity in vivo through a higher expression of vascularization-related genes. Overall, the novel engineered bone scaffold promises to serve as alternative candidates for bone tissue engineering applications.

Near-field electrospinning-enabled direct-write P(VDF-TrFE) nano/micro-fiber-based piezoelectric film for a high-performance airflow sensor

Airflow sensor is a crucial component in many engineering settings, such as sustainable energy utilization, environmental monitoring, weather forecasting, and aerospace engineering. However, few developed airflow sensors can exhibit decent sensing capability towards ultra-low-speed airflows owing to the performance limitations of sensing elements. In this work, we adopt a near-field electrospinning method to direct-write highly aligned poly(vinylidene-trifluoroethylene) (P(VDF-TrFE)) nano/micro fibers onto a flexible substrate with pre-designed interdigital electrodes to form a piezoelectric sensing film (PSF); the fabricated PSF is then used for airflow sensing application. We theoretically derive the output voltage of a single P(VDF-TrFE) fiber on the PSF under airflow loading, and numerically elucidate the dependency of output voltage on device and experimental parameters. Experimental results show that the lower detection limit of our airflow sensor can be as low as 0.3 m/s with the sensitivity of up to 15 mV/(m/s), which has been hardly accomplished in previous piezoelectric airflow sensors. This study not only presents a high-performance piezoelectric nano/micro-fiber-integrated airflow sensor, but also provides a universal electromechanical analysis method for piezoelectric fiber-based flexible electronics under pressure loading.