Co-assembling bioactive short peptide nanofibers coated silk scaffolds induce neurite outgrowth of PC12 cells.

Controlling biomolecular-cell interactions is crucial for the design of scaffolds for tissue engineering (TE). Regenerated silk fibroin (RSF) has been extensively used as TE scaffolds, however, RSF showed poor attachment of neuronal cells, such as rat pheochromocytoma (PC12) cells. In this work, amphiphilic peptides containing a hydrophobic isoleucine tail (I) and laminin or fibronectin derived peptides (IKVAV, PDSGR, YIGSR, RGDS and PHSRN) were designed for promoting scaffold-cell interaction.

Medium chain length polyhydroxyalkanoates as potential matrix materials for peripheral nerve regeneration.

Polyhydroxyalkanoates are natural, biodegradable, thermoplastic and sustainable polymers with a huge potential in fabrication of bioresorbable implantable devices for tissue engineering. We describe a comparative evaluation of three medium chain length polyhydroxyalkanoates (mcl-PHAs), namely poly(3-hydroxyoctanoate), poly(3-hydroxyoctanoate-co-3-hydoxydecanoate) and poly(3-hydroxyoctanoate-co-3-hydroxydecanoate-co-3-hydroxydodecanoate), one short chain length polyhydroxyalkanoate, poly(3-hydroxybutyrate), P(3HB) and synthetic aliphatic polyesters (polycaprolactone and polylactide) with a specific focus on nerve regeneration, due to mechanical properties of mcl-PHAs closely matching nerve tissues. biological studies with NG108-15 neuronal cell and primary Schwann cells did not show a cytotoxic effect of the materials on both cell types.

Aminosilane Functionalized Aligned Fiber PCL Scaffolds for Peripheral Nerve Repair.

Silane modification is a simple and cost-effective tool to modify existing biomaterials for tissue engineering applications. Aminosilane layer deposition has previously been shown to control NG108-15 neuronal cell and primary Schwann cell adhesion and differentiation by controlling deposition of ─NH groups at the submicron scale across the entirety of a surface by varying silane chain length. This is the first study toreport depositing 11-aminoundecyltriethoxysilane (CL11) onto aligned Polycaprolactone (PCL) scaffolds for peripheral nerve regeneration.

Aligned Polyhydroxyalkanoate Blend Electrospun Fibers as Intraluminal Guidance Scaffolds for Peripheral Nerve Repair.

The use of nerve guidance conduits (NGCs) to treat peripheral nerve injuries is a favorable approach to the current "gold standard" of autografting. However, as simple hollow tubes, they lack specific topographical and mechanical guidance cues present in nerve grafts and therefore are not suitable for treating large gap injuries (30-50 mm). The incorporation of intraluminal guidance scaffolds, such as aligned fibers, has been shown to increase neuronal cell neurite outgrowth and Schwann cell migration distances.

Selectively inhibiting malignant melanoma migration and invasion in an engineered skin model using actin-targeting dinuclear Ru-complexes.

Due to the poor prognosis of metastatic cancers, there is a clinical need for agents with anti-metastatic activity. Here we report on the anti-metastatic effect of a previously reported Ru(ii) complex [{(phen)Ru}(tpphz)], 1, that has recently been shown to disrupt actin fiber assembly. In this study, we investigated the anti-migratory effect of 1 and a close structural analogue, 2, on two highly invasive, metastatic human melanoma cell lines.

Polyhydroxyalkanoates and their advances for biomedical applications.

Polyhydroxyalkanoates (PHAs) are sustainable, versatile, biocompatible, and bioresorbable polymers that are suitable for biomedical applications. Produced via bacterial fermentation under nutrient-limiting conditions, they are uncovering a new horizon for devices in biomedical applications. A wide range of cell types including bone, cartilage, nerve, cardiac, and pancreatic cells, readily attach grow and are functional on PHAs.

A Dinuclear Osmium(II) Complex Near-Infrared Nanoscopy Probe for Nuclear DNA.

With the aim of developing photostable near-infrared cell imaging probes, a convenient route to the synthesis of heteroleptic Os complexes containing the Os(TAP) fragment is reported. This method was used to synthesize the dinuclear Os complex, [{Os(TAP)}tpphz] (where tpphz = tetrapyrido[3,2-a:2',3'-c:3″,2''-h:2‴,3'''-j]phenazine and TAP = 1,4,5,8- tetraazaphenanthrene). Using a combination of resonance Raman and time-resolved absorption spectroscopy, as well as computational studies, the excited state dynamics of the new complex were dissected.

Cell guidance on peptide micropatterned silk fibroin scaffolds.

Guiding neuronal cell growth is desirable for neural tissue engineering but is very challenging. In this work, a self-assembling ultra-short surfactant-like peptide IK which possesses positively charged lysine head groups, and hydrophobic isoleucine tails, was chosen to investigate its potential for guiding neuronal cell growth. The peptides were able to self-assemble into nanofibrous structures and interact strongly with silk fibroin (SF) scaffolds, providing a niche for neural cell attachment and proliferation.

Cost effective optimised synthetic surface modification strategies for enhanced control of neuronal cell differentiation and supporting neuronal and Schwann cell viability.

Enriching a biomaterial surface with specific chemical groups has previously been considered for producing surfaces that influence cell response. Silane layer deposition has previously been shown to control mesenchymal stem cell adhesion and differentiation. However, it has not been used to investigate neuronal or Schwann cell responses in vitro to date.

A Tuneable, Photocurable, Poly(Caprolactone)-Based Resin for Tissue Engineering-Synthesis, Characterisation and Use in Stereolithography.

Stereolithography is a useful additive manufacturing technique for the production of scaffolds for tissue engineering. Here we present a tuneable, easy-to-manufacture, photocurable resin for use in stereolithography, based on the widely used biomaterial, poly(caprolactone) (PCL). PCL triol was methacrylated to varying degrees and mixed with photoinitiator to produce a photocurable prepolymer resin, which cured under UV light to produce a cytocompatible material.

Bioresorbable and Mechanically Optimized Nerve Guidance Conduit Based on a Naturally Derived Medium Chain Length Polyhydroxyalkanoate and Poly(ε-Caprolactone) Blend.

Severe peripheral nerve injuries represent a large clinical problem with relevant challenges such as the development of successful synthetic scaffolds as substitutes to autologous nerve grafting. Numerous studies have reported the use of polyesters and type I collagen-based nerve guidance conduits (NGCs) to promote nerve regeneration through critical nerve defects while providing protection from external factors. However, none of the commercially available hollow bioresorbable NGCs have demonstrated superior clinical outcomes to an autologous nerve graft.

Biomimetic surface delivery of NGF and BDNF to enhance neurite outgrowth.

Treatment for peripheral nerve injuries includes the use of autografts and nerve guide conduits (NGCs). However, outcomes are limited, and full recovery is rarely achieved. The use of nerve scaffolds as a platform to surface immobilize neurotrophic factors and deliver locally is a promising approach to support neurite and nerve outgrowth after injury.

UV-Casting on Methacrylated PCL for the Production of a Peripheral Nerve Implant Containing an Array of Porous Aligned Microchannels.

Peripheral nerves are basic communication structures guiding motor and sensory information from the central nervous system to receptor units. Severed peripheral nerve injuries represent a large clinical problem with relevant challenges to successful synthetic nerve repair scaffolds as substitutes to autologous nerve grafting. Numerous studies reported the use of hollow tubes made of synthetic polymers sutured between severed nerve stumps to promote nerve regeneration while providing protection for external factors, such as scar tissue formation and inflammation.

Modulation of neuronal cell affinity of composite scaffolds based on polyhydroxyalkanoates and bioactive glasses.

The biocompatibility and neuron regenerating properties of various bioactive glass (BG)/polyhydroxyalkanoate (PHA) blend composites were assessed in order to study their suitability for peripheral nerve tissue applications, specifically as lumen structures for nerve guidance conduits. BG/PHA blend composites were fabricated using Bioactive glass® 45 S5 (BG1) and BG 1393 (BG2) with the 25:75 poly(3-hydroxyoctanoate/poly3-hydroxybutyrate), 25:75 P(3HO)/P(3HB) blend (PHA blend). Various concentrations of each BG (0.

A Dinuclear Ruthenium(II) Complex Excited by Near-Infrared Light through Two-Photon Absorption Induces Phototoxicity Deep within Hypoxic Regions of Melanoma Cancer Spheroids.

The dinuclear photo-oxidizing Ru complex [{Ru(TAP)}(tpphz)] (TAP = 1,4,5,8- tetraazaphenanthrene, tpphz = tetrapyrido[3,2-:2',3'-:3″,2''-:2‴,3'''-]phenazine), , is readily taken up by live cells localizing in mitochondria and nuclei. In this study, the two-photon absorption cross section of is quantified and its use as a two-photon absorbing phototherapeutic is reported. It was confirmed that the complex is readily photoexcited using near-infrared, NIR, and light through two-photon absorption, TPA.

Correction: A dinuclear ruthenium(ii) phototherapeutic that targets duplex and quadruplex DNA.

[This corrects the article DOI: 10.1039/C8SC05084H.].

Unidirectional neuronal cell growth and differentiation on aligned polyhydroxyalkanoate blend microfibres with varying diameters.

Polyhydroxyalkanoates (PHAs) are a family of prokaryotic-derived biodegradable and biocompatible natural polymers known to exhibit neuroregenerative properties. In this work, poly(3-hydroxybutyrate), P(3HB), and poly(3-hydroxyoctanoate), P(3HO), have been combined to form blend fibres for directional guidance of neuronal cell growth and differentiation. A 25:75 P(3HO)/P(3HB) blend (PHA blend) was used for the manufacturing of electrospun fibres as resorbable scaffolds to be used as internal guidance lumen structures in nerve conduits.

A dinuclear ruthenium(ii) phototherapeutic that targets duplex and quadruplex DNA.

With the aim of developing a sensitizer for photodynamic therapy, a previously reported luminescent dinuclear complex that functions as a DNA probe in live cells was modified to produce a new iso-structural derivative containing Ru(TAP) fragments (TAP = 1,4,5,8-tetraazaphenanthrene). The structure of the new complex has been confirmed by a variety of techniques including single crystal X-ray analysis. Unlike its parent, the new complex displays Ru → L-based MLCT emission in both MeCN and water.

Additive manufactured biodegradable poly(glycerol sebacate methacrylate) nerve guidance conduits.

Unlabelled: Entubulating devices to repair peripheral nerve injuries are limited in their effectiveness particularly for critical gap injuries. Current clinically used nerve guidance conduits are often simple tubes, far stiffer than that of the native tissue. This study assesses the use of poly(glycerol sebacate methacrylate) (PGSm), a photocurable formulation of the soft biodegradable material, PGS, for peripheral nerve repair.

An Improved Methodology to Visualise Tumour Induced Changes in Vasculature Using the Chick Chorionic Allantoic Membrane Assay.

Background/aim: Decreasing the vascularity of a tumour has proven to be an effective strategy to suppress tumour growth and metastasis. Anti-angiogenic therapies have revolutionized the treatment of advanced-stage cancers, however there is still demand for further improvement. This necessitates new experimental models that will allow researchers to reliably study aspects of angiogenesis.

Pre-clinical evaluation of advanced nerve guide conduits using a novel 3D testing model.

Autografts are the current gold standard for large peripheral nerve defects in clinics despite the frequently occurring side effects like donor site morbidity. Hollow nerve guidance conduits (NGC) are proposed alternatives to autografts, but failed to bridge gaps exceeding 3 cm in humans. Internal NGC guidance cues like microfibres are believed to enhance hollow NGCs by giving additional physical support for directed regeneration of Schwann cells and axons.

Oxygen Mapping of Melanoma Spheroids using Small Molecule Platinum Probe and Phosphorescence Lifetime Imaging Microscopy.

Solid tumours display varied oxygen levels and this characteristic can be exploited to develop new diagnostic tools to determine and exploit these variations. Oxygen is an efficient quencher of emission of many phosphorescent compounds, thus oxygen concentration could in many cases be derived directly from relative emission intensity and lifetime. In this study, we extend our previous work on phosphorescent, low molecular weight platinum(II) complex as an oxygen sensing probe to study the variation in oxygen concentration in a viable multicellular 3D human tumour model.

Inkjet printing Schwann cells and neuronal analogue NG108-15 cells.

Porcine Schwann cells and neuronal analogue NG108-15 cells were printed using a piezoelectric-inkjet-printer with a nozzle diameter of 60 μm, within the range of 70-230 V, with analysis of viability and quality after printing. Neuronal and glial cell viabilities of >86% and >90% were detected immediately after printing and no correlation between voltage applied and cell viability could be seen. Printed neuronal cells were shown to produce neurites earlier compared to controls, and over several days, produced longer neurites which become most evident by day 7.

Decellularisation and histological characterisation of porcine peripheral nerves.

Peripheral nerve injuries affect a large proportion of the global population, often causing significant morbidity and loss of function. Current treatment strategies include the use of implantable nerve guide conduits (NGC's) to direct regenerating axons between the proximal and distal ends of the nerve gap. However, NGC's are limited in their effectiveness at promoting regeneration Current NGCs are not suitable as substrates for supporting either neuronal or Schwann cell growth, as they lack an architecture similar to that of the native extracellular matrix (ECM) of the nerve.