Polycaprolactone Surface Research Articles

Chemical Immobilization of Carboxymethyl Chitosan on Polycaprolactone Nanofibers as Osteochondral Scaffolds

Carboxymethyl chitosan (CMC) as a bio-based osteochondral inductive material was chemically immobilized on the surface of polycaprolactone (PCL) nanofibers to fabricate scaffolds for osteochondral tissue engineering applications. The chemical immobilization process included the aminolysis of ester bonds and bonding of the primary amines with glutaraldehyde as a coupling agent. The SEM and FTIR results confirmed the successfulness of the CMC immobilization. The fabricated scaffolds presented cell viabilities of > 82% and supported the attachment and proliferation of the human bone marrow mesenchymal stem cells (hBM-MSCs). The CMC-immobilized scaffolds concentration dependently induced the diverse osteochondral differentiation pathways for the hBM-MSCs without using any external differential agents. According to the Alcian Blue and Alizarin Red staining and immunocytochemistry results, scaffolds with a higher content of CMC presented more chondro-inductivity and less osteoinductivity. Thus, the CMC-immobilized scaffolds can be employed as great potential candidates for osteochondral tissue engineering applications.

A mussel-bioinspired coating strategy to licence PCL osteoinductive activity for repairing bone defects

3,4-Dihydroxyphenylalanine (DOPA) is believed to play an essential role in the solidification and adhesion of liquid mussel adhesives; this thin polymer layer very tightly adheres to the surface of scaffolds, making it stable enough to prevent it from being peeled off. Fascinatingly, the deposition of DOPA on various types of surfaces via the self-polymerization of DOPA under alkaline conditions is a simple approach for creating biomimetic coatings. In this study, DOPA derivatives were used as monomers to form primary coatings on polycaprolactone (PCL) surfaces. After that, a second chemical crosslinking method was utilized to graft alendronate (AL) on the DOPA coatings via genipin (GP) crosslinking (D-PCL@AL). X-ray photoelectron spectroscopy, Fourier transform infrared reflection and scanning electron microscopy analyses indicated that AL was distributed homogeneously on the surface of PCL. This new organic–inorganic hybridized coating could support EMSC growth and osteogenic differentiation. Additionally, animal studies were also performed to verify the function of D-PCL@AL in promoting osteogenesis. The method is simple, cheap and highly efficient, which makes it very convenient to apply on a large scale.

Truncated vascular endothelial cadherin enhances rapid endothelialization of small diameter synthetic vascular grafts

Complete and rapid endothelialization is critical to the long-term performance of synthetic vascular grafts. A fully formed endothelium is resistant to thrombosis and mitigates the development of neointimal hyperplasia, the dominant modes of acute and chronic graft failure, respectively. Significant research efforts aim to develop strategies which enhance graft endothelialization through the incorporation of surface ligands that promote the attachment and growth of endothelial cells. In native vessels these functions are regulated by the adhesion molecule vascular endothelial cadherin (VE-Cad). VE-Cad is exclusive to endothelial cells and possesses high self-affinity, forming homodimers with VE-Cad on adjacent endothelial cells. Leveraging this targeted binding ability, we developed a graft functionalization approach using a recombinant truncated form of VE-Cad (VEtr). VEtr contains only the domains responsible for self-interaction, recognition and adhesion. Using the plasma functionalization technique, plasma immersion ion implantation (PIII) technique we immobilize VEtr onto the surface of electrospun polycaprolactone (PCL). VEtr scaffolds achieved a nearly 2-fold increase in attachment and spreading, and a 2.5-fold increase in proliferation of human coronary artery endothelial cells (HCAECs) compared with control scaffolds in vitro. Following 14-day implantation in a mouse carotid artery model, VEtr grafts showed ∼90% CD31-positive endothelial coverage. The benefits of this enhanced endothelialization included an ∼88% reduction in fibrin deposition (early thrombosis) as well as ∼63% reduction in macrophage recruitment (early neointimal hyperplasia). These findings highlight VEtr functionalization as a promising approach for rapid graft endothelialization which may potentially improve the long-term performance of synthetic vascular grafts.

Fabrication of Antimicrobial Multilayered Nanofibrous Scaffolds-Loaded Drug via Electrospinning for Biomedical Application.

Nanofibers prepared by biobased materials are widely used in the field of biomedicine, owing to outstanding biocompatibility, biodegradable characters, and excellent mechanical behavior. Herein, we fabricated multilayered nanofibrous scaffolds in order to improve the performance of drug delivery. The composite layer-by-layer scaffolds were incorporated by hydrophobic poly(l-lactic acid) (PLA): polycaprolactone (PCL) and hydrophilic poly(vinyl alcohol) (PVA) nanofibers via multilayer electrospinning. Morphological and structural characteristics of the developed scaffolds measured by scanning electron microscopy (SEM), and transmission electron microscopy (TEM) confirmed smooth and uniform fibers ranging in nanometer scale. The differences in contact angles and Fourier transform infrared spectrum (FTIR) between single-layered PVA nanofibers and multilayered scaffolds verified the existence of PLA: PCL surface. In vitro biodegradable and drug release analysis depicted multilayered scaffolds had good biodegradability and potential for medical application. Due to the model drug incorporation, scaffolds exhibited good antibacterial activity against Escherichia coli and Staphylococcus aureus by the zone of inhibition test. These results revealed that the multilayered scaffolds were proved to be desirable antibacterial materials for biomedical application.

Formation of diamond like carbon films on materials for medical application

The aim of this experimental work is to identify how the surfaces of materials that are most often used inmedical implants and prostheses, affect the properties of the deposited amorphous carbon films. The DLCfilms were formed on the stainless steel, aluminium, polyetheretherketone (PEEK) and polycaprolactone(PCL) surfaces by PECVD method using C2H2 gas plasma and their properties was compared with the filmsdeposited on silicon. The differences of the films properties were determined by a null-ellipsometry and Ramanspectroscopy. It was found that the thicknesses of the carbon coatings deposited on metallic substratesare larger than on the silicon when the deposition conditions were the same. When the films are formed athigh bias voltage the refractive index of the DLC films deposited on stainless steel are lower compared tothe coatings on silicon but the extinction coefficients are higher. Raman spectra shows that sp2 bonds concentrationis higher in this case. When the ion energy is lowest (bias voltage -400 V), Raman spectroscopyshows that D peak isn’t observed on the Si-deposited carbon coating, while the typical carbon amorphouscoating is formed on the Al substrate. The thickness of amorphous carbon coatings deposited on the polymersdepends on the bias voltage, and the optical properties depend on the type of polymer. The coatingsdeposited on PCL have a much higher refractive index than on PEEK. Key words: amorphous carbon films, steel, aluminum, polyetheretherketone, polycaprolactone, Ramanspectroscopy.

Gelatin coating promotes in situ endothelialization of electrospun polycaprolactone vascular grafts

Rapid endothelialization is crucial for in situ tissue engineering vascular grafts to prevent graft failure in the long-term. Gelatin is a promising nature material that can promote endothelial cells (ECs) adhesion, proliferation, and migration. In this study, the internal surface of electrospun polycaprolactone (PCL) vascular grafts was coated with gelatin. Endothelialization and vascular wall remolding were investigated by imaging and histological studies in the rat abdominal aorta replacement model. The endothelialization of heparinized gelatin-coated PCL (GP-H) vascular grafts was more rapid and complete than heparinized PCL (P-H) grafts. Intimal hyperplasia was milder in the GP-H vascular grafts than the P-H vascular grafts in the long-term. Meanwhile, smooth muscle cells (SMCs) and extracellular matrix (ECM) regeneration were better in the GP-H vascular grafts. By comparison, an aneurysm was observed in the P-H group in 6 months. Calcification was observed in both groups. All vascular grafts were patient after implantation in both groups. Our results showed that gelatin coating on the internal surface of PCL grafts is a simple and effective way to promote endothelialization. A more rapid endothelialization and complete endothelium can inhibit intimal hyperplasia in the long-term.

Investigation and comparison of new galactosylation methods on PCL/chitosan scaffolds for enhanced liver tissue engineering

In liver tissue engineering, improving the ability of the scaffold to increase the tendency of cells to grow and proliferate is very important. In this study, new methods for modifying the surface of Polycaprolactone (PCL)/Chitosan (Cs) nanofiber for use in liver tissue engineering have been proposed. Galactosylation of chitosan was performed in three ways. According to the FE-SEM, FTIR, NMR and DSC analysis, presence of galactose in uniform nanofibers confirmed and led to a decrease in crystallinity. The hydrophobicity of the scaffolds by contact angle showed that the scaffold with galactosylated after electrospinning, had the highest contact angle of 82.22 ± 2° compared to raw scaffold with 98.52 ± 4°. According to the results of degradation in PBS, the highest rate of degradation was observed in scaffolds that were galactosylated after electrospinning. By culturing HepG2 cells on and based on the results of SEM and MTT analysis, found that the presence of galactose in the scaffolds significantly increased cell growth and proliferation without any toxicity. The immersion method shows a greater ability to improve the growth of liver cells. Also, using in-situ way due to the roughness created in this method may lead to better results especially for in-vivo tests.

A simple route to functionalising electrospun polymer scaffolds with surface biomolecules

Surface functionalisation of polymeric electrospun scaffolds with therapeutic biomolecules is often explored in regenerative medicine and tissue engineering. However, the bioconjugation method must be carefully selected to prevent partial or full loss of activity of the biomolecule following chemical manipulation. Perfluorophenyl azide bearing a N‐hydroxysuccinimide (PFPA-NHS) active ester group is a versatile tool for UV-initiated covalent coupling of amine-containing molecules to hydrocarbon-based polymers, such as polydioxanone or polycaprolactone (PCL). This study therefore explored the feasibility of PFPA-NHS functionalisation of electrospun PCL scaffolds with model biomolecules. Protein conjugation was extensively explored using fluorescence staining and attachment studies, confirming the retention of amine coupling capability following photografting of PFPA-NHS to the PCL surface. The effect of the washing method used to remove unreacted PFPA was explored in Caco-2 cell viability studies, and it was determined that sonication washing is required to avoid cell death. A model enzyme, catalase, was then successfully attached to the surface of PCL scaffolds for potential applications in oncological photodynamic therapy. Catalase retained its enzymatic activity following attachment to the fibres and the majority of the enzyme (~60%) remained bound to the fibre after incubation in an aqueous environment for six days. The anticipated prolonged presentation and sustained release of proteins as a result of PFPA-NHS conjugation could be advantageous in progressing protein-based therapies.

Protein repellent anti-coagulative mixed-charged cellulose derivative coatings

This study describes the formation of cellulose based polyelectrolyte charge complexes on the surface of biodegradable polycaprolactone (PCL) thin films. Anionic sulphated cellulose (CS) and protonated cationic amino cellulose (AC) were used to form these complexes with a layer-by-layer coating technique. Both polyelectrolytes were analyzed by charge titration methods to elucidate their pH-value dependent protonation behavior. A quartz crystal microbalance with dissipation (QCM-D) in combination with X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) were used to follow the growth, stability and water content of up to three AC/CS bi-layers in aqueous environment. This was combined with coagulation studies on one, two and three bilayers of AC/CS, measuring the thrombin formation rate and the total coagulation time of citrated blood plasma with QCM-D. Stable mixed charged bilayers could be prepared on PCL and significantly higher masses of AC than of CS were present in these complexes. Strong hydration due to the presence of ammonium and sulphate substituents on the backbone of cellulose led to a significant BSA repellent character of three bilayers of AC/CS coatings. The total plasma coagulation time was increased in comparison to neat PCL, indicating an anticoagulative nature of the coatings. Surprisingly, a coating solely composed of an AC layer significantly prolonged the total coagulation time on the surfaces although it did not prevent fibrinogen deposition. It is suggested that these cellulose derivative-based coatings can therefore be used to prevent unwanted BSA deposition and fibrin clot formation on PCL to foster its biomedical application.

Insights into the biomechanical properties of plasma treated 3D printed PCL scaffolds decorated with gold nanoparticles

Tissue engineered constructs having desired biomimetic and mechanical properties emerged due to the complexities involved in conventional skin grafting. They facilitate tissue regeneration without compromising mechanical properties. Herein, we report the fabrication of polycaprolactone (PCL) scaffold by fused deposition modeling and immobilization of gold nanoparticles onto the polymer surface after modifying the PCL surface using plasma polymerization. 3D printed PCL scaffolds inlaid with gold nanoparticles (Au-PCL) were characterized for their structural and mechanical properties using FESEM, and nano-indentation. The surface chemistry was analyzed using X-ray photon electron spectroscopy (XPS), wettability was determined using water contact angle studies and surface topography was imaged by atomic force microscopy (AFM). The surface modification of 3D printed scaffolds significantly improved their hydrophilicity suggesting that hydrophobicity which restricts the use of PCL in biological applications could be overcome by plasma modification. Nanoindentation studies showed that Au-PCL scaffolds exhibited remarkable enhancement in mechanical properties with reduced Young's modulus of 1.81 GPa. Biocompatibility was assessed by measuring cell viability, cell attachment and immune response. In vitro biocompatibility studies indicated good attachment of viable cells onto the gold nanoparticles incorporated 3D printed network. Immune response studies indicated that scaffolds did not enhance the production of pro-inflammatory cytokines such as TNF-α, IL-8 and IL-β. Collectively, plasma modification and surface immobilization of gold nanoparticles onto the 3D printed PCL scaffold is a simple and cost-effective technique to enhance the mechanical properties and biocompatibility of hydrophobic scaffolds like PCL, thereby making this technique a very promising tool for futuristic applications of scaffolds.

Long-term hydrolytic degradation study of polycaprolactone films and fibers grafted with poly(sodium styrene sulfonate): Mechanism study and cell response.

Polycaprolactone (PCL) is a widely used biodegradable polyester for tissue engineering applications when long-term degradation is preferred. In this article, we focused on the analysis of the hydrolytic degradation of virgin and bioactive poly(sodium styrene sulfonate) (pNaSS) functionalized PCL surfaces under simulated physiological conditions (phosphate buffer saline at 25 and 37 °C) for up to 120 weeks with the aim of applying bioactive PCL for ligament tissue engineering. Techniques used to characterize the bulk and surface degradation indicated that PCL was hydrolyzed by a bulk degradation mode with an accelerated degradation-three times increased rate constant-for pNaSS grafted PCL at 37 °C when compared to virgin PCL at 25 °C. The observed degradation mechanism is due to the pNaSS grafting process (oxidation and radical polymerization), which accelerated the degradation until 48 weeks, when a steady state is reached. The PCL surface was altered by pNaSS grafting, introducing hydrophilic sulfonate groups that increase the swelling and smoothing of the surface, which facilitated the degradation. After 48 weeks, pNaSS was largely removed from the surface, and the degradation of virgin and pNaSS grafted surfaces was similar. The cell response of primary fibroblast cells from sheep ligament was consistent with the surface analysis results: a better initial spreading of cells on pNaSS surfaces when compared to virgin surfaces and a tendency to become similar with degradation time. It is worthy to note that during the extended degradation process the surfaces were able to continue inducing better cell spreading and preserve their cell phenotype as shown by collagen gene expressions.

Synergistic effects of gelatin and nanotopographical patterns on biomedical PCL patches for enhanced mechanical and adhesion properties

Biomedical patches have been known as important biomaterial-based medical devices for the clinical treatment of tissue and organ diseases. Inspired by the extracellular matrix-like aligned nanotopographical pattern as well as the unique physical and biocompatible properties of gelatin, we developed strength-enhanced biomedical patches by coating gelatin onto the nanopatterned surface of polycaprolactone (PCL). The relative contributions of the nanotopographical pattern (physical factor) and gelatin coating (chemical factor) in enhancing the mechanical and adhesive properties of PCL were quantitatively investigated. The nanotopographical pattern increased the surface area of PCL, allowing more gelatin to be coated on its surface. The biomedical patch made from gelatin-coated nanopatterned PCL showed strong mechanical and adhesive properties (tensile strength: ~14.5 MPa; Young's modulus: ~60.2 MPa; and normal and shear adhesive forces: ~1.81 N/cm2 and ~352.3 kPa) as well as good biocompatibility. Although the nanotopographical pattern or gelatin coating alone could enhance these physical properties of PCL in both dry and wet environmental conditions, both factors in combination further strengthened the properties, indicating the importance of synergistic cues in driving the mechanical behavior of biomedical materials. This strength-enhanced biomedical patch will be especially useful for the treatment of tissues such as cartilage, tendon, and bone.

Evaluation of a peptide motif designed for protein tethering to polymer surfaces

In search for peptide motifs that allow us to efficiently tether fusion proteins onto polymer surfaces, we designed a KLKLKLKLKL (KL5) decapeptide in which basic and hydrophobic amino acids were alternately linked. By means of genetic engineering technology together with a bacterial expression system, the KL5 fusions of epidermal growth factor (EGF), basic fibroblast growth factor, and stromal cell-derived factor-1α were prepared together with their control counterparts without KL5. The adsorption experiments were performed for these fusion proteins on the surface of polystyrene, hydrophilized polystyrene, and polycaprolactone by surface plasmon resonance analysis. To understand the results of the binding assays, the structure of the fusion proteins was predicted by ab initio computer simulation and analyzed empirically by circular dichroism spectroscopy. The result of structural analyses suggested that the KL5 peptide is exposed to the outside and has a negligible effect on the structure of the protein partners. However, it was found that the efficiency of KL5 as a peptide motif greatly depends on protein partners. Our results showed that KL5 exerts most effectively its function as a peptide motif when fused to acidic proteins such as EGF. Indeed, the number of living human mesenchymal stem cells determined after 7-day culture was larger on the polystyrene and polycaprolactone surfaces with EGF tethered through the KL5 peptide than control surfaces. According to the results obtained in this study, we conclude that KL5 is useful as a peptide motif for tethering a specific class of protein partners.

A PCL/cellulose coil-shaped scaffold via a modified electrohydrodynamic jetting process

ABSTRACT Scaffolds are regarded as a key factor for tissue engineering as they provide a three-dimensional structural frame for host cells to attach, proliferate, and differentiate. Recently, 3D bioprinting has enabled the quick and versatile fabrication of various architectures of micro/macroscale scaffolds, but there remain obstacles to successful tissue regeneration, such as large strut diameter and simple pore geometry and distribution. To overcome these deficiencies, we propose a new scaffold, which was fabricated using polycaprolactone (PCL)/cellulose and electrohydrodynamic jetting (EHDJ), composed of a spring-shaped strut and controllable macro/micropores. In this work, PCL provided reasonable mechanical strength and synergistic effects with cellulose, which homogeneously covered the PCL surface. Furthermore, the homogeneously distributed cellulose promoted meaningful cellular activities. By manipulating various processing parameters, we fabricated a stable coil-shaped scaffold and evaluated it for physical characteristics and in vitro cellular activities, including osteogenic activities, using MG63 cells. Consequently, the coil-shaped scaffold exhibited a significantly higher degree of cellular activity than the controls (PCL coil-shaped scaffold and PCL coil-shaped scaffold dipped in cellulose). Based on our results, the coil-shaped structure could represent a scaffold with high potential for use in hard tissue regeneration.

Diazonium chemistry surface treatment of piezoelectric polyhydroxybutyrate scaffolds for enhanced osteoblastic cell growth

Biodegradable piezoelectric 3D polymer scaffolds attract great attention due to possibilities to mimic the functional and mechanical properties of the extracellular matrix, avoiding secondary surgery, and electrically stimulated tissue repair. However, the preservation of piezoelectric response and improvement of wettability of hydrophobic fibrous polymer scaffolds, limiting their application in tissue engineering and regenerative medicine, is a challenge. Here, a facile and mild approach is presented to improve wettability and cell spreading on the surface of piezoelectric polyhydroxybutyrate (PHB) and non-piezoelectric polycaprolactone (PCL) scaffolds. The surface of electrospun 3D fibrous scaffolds was modified by 3,4-dicarboxybenzenediazonium tosylate (ADT-(COOH)2) via photo-induced formation of aryl radicals under ultraviolet irradiation. According to scanning electron microscopy and x-ray diffraction analyses, the intrinsic structure of 3D scaffolds remains unaffected after the treatment. Meanwhile, the attachment of hydrophilic 3,4-dicaboxyphenyl groups to the surface led to an apparent decrease of the water contact angle from 127±4° to 82±1° for PCL and from 126±4° to 78±2° for PHB, i.e. resulting in the change of the scaffold's wettability from hydrophobic to hydrophilic. Furthermore, no aging of the improved wetting was observed for 21 days. The diazonium modification allows to preserve a pronounced piezoelectric response, since PHB scaffolds demonstrate a slightly reduced effective d33 from 2.5 ± 0.3 pC•N−1 to 2.1 ± 0.4 pC•N−1 and surface electric potential from 510±56 mV to 458±25 mV after surface treatment. At the same time, after C6H3-(COOH)2 grafting, osteoblastic cells were well-spread along the PCL and PHB fibrous scaffolds. Moreover, after 7 days of incubation, the cell density is increased on the surface of ADT-(COOH)2-treated fibers in comparison to that on pristine ones, while cells formed a distinct osteoblastic network.

Green and low-cost electrospun membranes from polycaprolactone/graphene oxide for Bisphenol A sensing

Herein, we proposed a green design for a low-cost sensor based on graphene oxide (GO) adsorbed onto the surface of electrospun polycaprolactone (PCL) fibers. Ultrathin fibers were produced via electrospinning of PCL/acetic acid solutions, while the GO was obtained via carbonization of citric acid molecules. This sensor has been applied for the electrochemical detection of Bisphenol A (BPA) in water, which is an endocrine disrupting compound (EDC) responsible for several damages in living organisms, even at very low concentrations. While the detection of EDCs is pervasive at traces amounts due to their broad composition, our PCL/GO sensors showed a high sensitivity for BPA with a very low detection limit of approximately 23 nM (3.3 σ/S). In addition, the sensor showed a good reproducibility with a 7.9% relative standard deviation (RSD), while the sensor RSD response to 2 µM BPA was 5.7% for seven successive measurements. These results open up a window of applications of this nanostructured material, by easily combining a biodegradable polyester with GO obtained via a green and cost-effectiveness process using a naturally occurring component from citrus fruits.

End-of-life evaluation and biodegradation of Poly(lactic acid) (PLA)/Polycaprolactone (PCL)/Microcrystalline cellulose (MCC) polyblends under composting conditions

The present study evaluates biodegradation of the polyblends of poly(lactic acid) (PLA), polycaprolactone (PCL) and microcrystalline cellulose (MCC) in different compositions and comparison of the properties of those blends with that of neat PLA and neat PCL. The samples were melt extruded and blended to evaluate the environmental fate of the polyblends under simulated composting conditions following the standard ASTM International D5338-15 protocol. It was seen that blends with a higher concentration of PCL and MCC in the PLA matrix showed higher carbon mineralization percentage in comparison to the blends having low PCL and MCC components. Molecular weight analysis of the samples showed a decrease in their weight due to chain scission mechanism leading to the formation of intermediates. Analytical techniques revealed the formation of microbial biofilms on the blended biopolymeric surfaces. Field emission scanning electron microscopy showed the formation of fibril-like structures by PLA, and the formation of rough patches on the PCL surface re-confirmed biodegradation of the samples. This work fuels interest in the material characterization of PLA/PCL/MCC based polyblends and helps in tuning the biodegradability of the studied samples according to the demands.

Manipulation of AgNPs coated on selenium/carbonated hydroxyapatite/ε-polycaprolactone nano-fibrous via pulsed laser deposition for wound healing applications

Manipulation of nano-fibrous structures that imitate the normal extracellular matrix is one of the promising approaches that were suggested recently in wound healing biomedical applications. Silver nanoparticles (AgNPs) were deposited at different times of exposure on the surface of polycaprolactone (PCL) electrospun fibers containing carbonated hydroxyapatite (CHAP) which is substituted partially via selenite ions. This deposition was carried out using PLD technique. The yield compositions were investigated structurally and morphologically and were investigated also for their attachment towards the human osteoblast cell line (HFB4) after 3 days of in vitro culture. HFB4 cells lines have proliferated grow and spread through the fibrous compositions. Also antibacterial activity was carried out against S. aureus and E-coli. Surface roughness was enhanced with time coating enlarging, where roughness average increased from 27 at no coating to 35 nm after 20 min coating time. On the other hand, the antibacterial activity reached around 45.0% at t = 20.0 min against E. coli compared with the ciprofloxacin activity, while it recorded 43.0% against S. aureus. Increasing the coating time of nanoparticles for AgNPs@Se-CHAP/PCL enhances both cell growth and bacterial inhibition, this enhancement emphasizes that AgNPs@Se-CHAP/PCL is a dual function biomaterial that could be suggested as a potential material for wound healing applications.

Three-dimensional directional nerve guide conduits fabricated by dopamine-functionalized conductive carbon nanofibre-based nanocomposite ink printing.

A potential issue in current nerve guides is that they do not transmit electrical nerve impulses between the distal and proximal end of an injured nerve, i.e. a synapse. Conductivity is a desirable property of an ideal nerve guide that is being considered for peripheral nerve regeneration. Most conductive polymers reported for the fabrication of tissue engineering scaffolds, such as polypyrrole and polyaniline, are non-biodegradable and possess weak mechanical properties, and thus cannot be fabricated into 3D structures. Herein, we have designed a new nanocomposite material composed of dopamine, carbon nanofibers (CNF) and polycaprolactone (PCL) for the fabrication of nerve conduits, which facilitates the growth and migration of neurons toward the targeted end of an injured nerve. This support and navigation of the scaffold leads to better sensory and motor function. The results showed that the mechanical properties of the printed PCL increased by 30% in comparison with the pure PCL film, which is comparable with human nerves. The in vitro cell study of human glioma cells showed that the printed lines provided support for neural cell attachment, migration and differentiation toward the targeted end. In contrast, in the absence of printed lines in the scaffold, the cells attach and grow in random directions, forming a flower shape (cell cluster) on the surface of PCL. Thus, the proposed scaffold is a promising candidate for nerve guide application based on its signal transmission and navigating neurons in a correct pathway towards the targeted end.

Biologically responsive, long-term release nanocoating on an electrospun scaffold for vascular endothelialization and anticoagulation.

A critical challenge to the development of tissue engineering small-diameter vascular grafts is to achieve rapid endothelialization and long-term anticoagulation. It is necessary to graft both adhesion and antithrombus factors onto the surface of polycaprolactone without burst release to promote endothelial cell affinity and antithrombogenicity. A bionic structure with a nanocoating that allows a biologically responsive, long-term release was employed in this work to enable the grafting of various bioactive molecules such as gelatin, polylysine, and heparin. This approach involved orienting the biomimetic vascular structures; the self-assembly grafting of gelatin, polylysine, and heparin nanoparticles; and genipin crosslinking to form a multiphase crosslinked nanocoating. In this biologically inspired design, vascular endothelialization and long-term anticoagulation were successfully induced through a matrix metallopeptidase 2 regulative mechanism by delivering both adhesion and antithrombus factors with a responsive, long-term release without burst release. The method provided a simple and effective approach for delivering dual factors for tissue engineering small-diameter vascular grafts.