Biogelx-IKVAV Is An Innovative Human Platelet Lysate-Adipose-Derived Stem Cells Delivery Strategy to Improve Peripheral Nerve Repair.

Adipose-derived stem cells (ADSC) are nowadays one of the most exploited cells in regenerative medicine. They are fast growing, capable of enhancing axonal elongation, support and locally stimulate Schwann cells (SCs), and protect de-innervated muscles from atrophy after a peripheral nerve injury. With the aim of developing a bio-safe, clinically translatable cell-therapy, we assessed the effect of ADSC pre-expanded with human platelet lysate in an rat model, delivering the cells into a 15 mm critical-size sciatic nerve defect embedded within a laminin-peptide-functionalized hydrogel (Biogelx-IKVAV) wrapped by a poly-ɛ-caprolactone (PCL) nerve conduit.

Tuning conductivity while maintaining mechanical properties in perylene bisimide hydrogels at physiological pH.

By using different salts as a method to achieve gelation of two different amino-acid-functionalised perylene bisimides, we were able to tune reduction potentials while maintaining the mechanical and optical properties of the system all at pH 7.4.

Isolation and Culture of Human Adipose-Derived Stem Cells With an Innovative Xenogeneic-Free Method for Human Therapy.

Considering the increasing impact of stem cell therapy, biosafety concerns have been raised regarding potential contamination or infection transmission due to the introduction of animal-derived products during in vitro manipulation. The xenogeneic components, such as collagenase or fetal bovine serum, commonly used during the cell isolation and expansion steps could be associated with the potential risks of immune reactivity or viral, bacterial, and prion infection in the receiving patients. Following good manufacturing practice guidelines, chemical tissue dissociation should be avoided, while fetal bovine serum (FBS) can be substituted with xenogeneic-free supplements.

Bioengineered nerve conduits and wraps for peripheral nerve repair of the upper limb.

Background: Traumatic peripheral nerve injury is common and incurs significant cost to individuals and society. Healing following direct nerve repair or repair with autograft is slow and can be incomplete. Several bioengineered nerve wraps or devices have become available as an alternative to direct repair or autologous nerve graft.

Human Platelet Lysate Acts Synergistically With Laminin to Improve the Neurotrophic Effect of Human Adipose-Derived Stem Cells on Primary Neurons .

Background: Despite the advancements in microsurgical techniques and noteworthy research in the last decade, peripheral nerve lesions have still weak functional outcomes in current clinical practice. However, cell transplantation of human adipose-derived stem cells (hADSC) in a bioengineered conduit has shown promising results in animal studies. Human platelet lysate (hPL) has been adopted to avoid fetal bovine serum (FBS) in consideration of the biosafety concerns inherent with the use of animal-derived products in tissue processing and cell culture steps for translational purposes.

Bandpass sorting of heterogeneous cells using a single surface acoustic wave transducer pair.

Separation and sorting of biological entities (viruses, bacteria, and cells) is a critical step in any microfluidic lab-on-a-chip device. Acoustofluidics platforms have demonstrated their ability to use physical characteristics of cells to perform label-free separation. Bandpass-type sorting methods of medium-sized entities from a mixture have been presented using acoustic techniques; however, they require multiple transducers, lack support for various target populations, can be sensitive to flow variations, or have not been verified for continuous flow sorting of biological cells.

Human platelet lysate as a potential clinical-translatable supplement to support the neurotrophic properties of human adipose-derived stem cells.

Background: The autologous nerve graft, despite its donor site morbidity and unpredictable functional recovery, continues to be the gold standard in peripheral nerve repair. Rodent research studies have shown promising results with cell transplantation of human adipose-derived stem cells (hADSC) in a bioengineered conduit, as an alternative strategy for nerve regeneration. To achieve meaningful clinical translation, cell therapy must comply with biosafety.

A novel poly-ε-lysine based implant, Proliferate®, for promotion of CNS repair following spinal cord injury.

The limited regenerative capacity of the CNS poses formidable challenges to the repair of spinal cord injury (SCI). Two key barriers to repair are (i) the physical gap left by the injury, and (ii) the inhibitory milieu surrounding the injury, the glial scar. Biomaterial implantation into the injury site can fill the cavity, provide a substrate for cell migration, and potentially attenuate the glial scar.

Numerical Determination of the Secondary Acoustic Radiation Force on a Small Sphere in a Plane Standing Wave Field.

Two numerical methods based on the Finite Element Method are presented for calculating the secondary acoustic radiation force between interacting spherical particles. The first model only considers the acoustic waves scattering off a single particle, while the second model includes re-scattering effects between the two interacting spheres. The 2D axisymmetric simplified model combines the Gor'kov potential approach with acoustic simulations to find the interacting forces between two small compressible spheres in an inviscid fluid.

Controlling fluid flow to improve cell seeding uniformity.

Standard methods for seeding monolayer cell cultures in a multiwell plate or dish do not uniformly distribute cells on the surface. With traditional methods, users find aggregation around the circumference, in the centre, or a combination of the two. This variation is introduced due to the macro scale flow of the cell seeding suspension, and movement of the dish before cells can settle and attach to the surface.

Synthesis and cellular penetration properties of new phosphonium based cationic amphiphilic peptides.

A new category of phosphonium based cationic amphiphilic peptides has been developed and evaluated as potential antimicrobial peptides and cell penetrating peptides. The required building blocks were conveniently accessible from cysteine and could be applied in a solid phase peptide synthesis protocol for incorporation into peptide sequences. Evaluation of the antimicrobial properties and cellular toxicity of these phosphonium based peptides showed that these "soft" cationic side-chain containing peptides have poor antimicrobial properties and most of them were virtually non toxic (on HEK cells tested at 256 and 512 μM) and non-haemolytic (on horse erythrocytes tested at 512 μM), hinting at an interesting potential application as cell penetrating peptides.

The biomechanical role of overall-shape transformation in a primitive multicellular organism: A case study of dimorphism in the filamentous cyanobacterium Arthrospira platensis.

Morphological transformations in primitive organisms have long been observed; however, its biomechanical roles are largely unexplored. In this study, we investigate the structural advantages of dimorphism in Arthrospira platensis, a filamentous multicellular cyanobacterium. We report that helical trichomes, the default shape, have a higher persistence length (Lp), indicating a higher resistance to bending or a large value of flexural rigidity (kf), the product of the local cell stiffness (E) and the moment of inertia of the trichomes' cross-section (I).

Particle separation by phase modulated surface acoustic waves.

High efficiency isolation of cells or particles from a heterogeneous mixture is a critical processing step in lab-on-a-chip devices. Acoustic techniques offer contactless and label-free manipulation, preserve viability of biological cells, and provide versatility as the applied electrical signal can be adapted to various scenarios. Conventional acoustic separation methods use time-of-flight and achieve separation up to distances of quarter wavelength with limited separation power due to slow gradients in the force.

Microtopographical cues promote peripheral nerve regeneration via transient mTORC2 activation.

Unlabelled: Despite microsurgical repair, recovery of function following peripheral nerve injury is slow and often incomplete. Outcomes could be improved by an increased understanding of the molecular biology of regeneration and by translation of experimental bioengineering strategies. Topographical cues have been shown to be powerful regulators of the rate and directionality of neurite regeneration, and in this study we investigated the downstream molecular effects of linear micropatterned structures in an organotypic explant model.

Nacre Topography Produces Higher Crystallinity in Bone than Chemically Induced Osteogenesis.

It is counterintuitive that invertebrate shells can induce bone formation, yet nacre, or mother of pearl, from marine shells is both osteoinductive and osteointegrative. Nacre is composed of aragonite (calcium carbonate) and induces production of vertebrate bone (calcium phosphate). Exploited by the Mayans for dental implants, this remarkable phenomenon has been confirmed in vitro and in vivo, yet the characteristic of nacre that induces bone formation remains unknown.

Mechanical behaviour of biodegradable AZ31 magnesium alloy after long term in vitro degradation.

Biodegradable magnesium alloys including AZ31 are exciting candidates for temporary implants as they eliminate the requirement for surgical removal, yet have higher mechanical properties than degradable polymers. However, the very long term mechanical properties and degradation of these alloys have not been fully characterized. The tensile, bending and corrosion behaviour of biodegradable AZ31 Mg alloy specimens have been investigated for up to 9months in vitro in phosphate buffered saline (PBS).

When the going gets rough - studying the effect of surface roughness on the adhesive abilities of tree frogs.

Tree frogs need to adhere to surfaces of various roughnesses in their natural habitats; these include bark, leaves and rocks. Rough surfaces can alter the effectiveness of their toe pads, due to factors such as a change of real contact area and abrasion of the pad epithelium. Here, we tested the effect of surface roughness on the attachment abilities of the tree frog .

Contactless Acoustic Manipulation and Sorting of Particles by Dynamic Acoustic Fields.

This paper presents a contactless, acoustic technique to manipulate and sort particles of varying size in both liquid and air media. An acoustic standing wave is generated by the superposition of counterpropagating waves emitted by two opposing emitters. The acoustic radiation force traps the smallest particles at the pressure nodes of the acoustic standing wave.

Production of Nanoscale Vibration for Stimulation of Human Mesenchymal Stem Cells.

Mechanical stimulation is becoming a common technique for manipulating cell behaviour in bioengineering with applications in tissue engineering and possibly regenerative therapy. Living organisms show biological responses in vivo and in vitro to various types of mechanical stimulation including vibration. The development of apparatus to produce vertical motions of nanoscale amplitude is detailed and their effect on mouse endothelial (Le2) and human mesenchymal stem cells (hMSCs) is investigated.

Directed nerve regeneration enabled by wirelessly powered electrodes printed on a biodegradable polymer.

Wirelessly directed nerve regeneration: inductively powered electrical stimulation circuits on the biodegradable polymer polycaprolactone demonstrate directed regeneration of sensory neurons from a dorsal root ganglion. These circuits, produced using a unique transfer printing process, illustrate progress towards the use of electrical stimulation systems on biodegradable materials to improve peripheral nerve repair functional outcomes.

Protein-mediated dethreading of a biotin-functionalised pseudorotaxane.

In this article, we describe the synthesis of new biotin-functionalised naphthalene derivatives 3 and 4 and their complexation behaviour with avidin and neutravidin using a range of analytical techniques. We have shown using 2-(4'-hydroxyazobenzene)benzoic acid displacement and ITC experiments, that compounds 3 and 4 have the propensity to form reasonably high-affinity bioconjugates with avidin and neutravidin. We have also demonstrated using (1)H NMR, UV-vis and fluorescence spectroscopy that the naphthalene moiety of 3 and 4 facilitates the formation of pseudorotaxane-like structures with 1 in water.

Development of a novel 3D culture system for screening features of a complex implantable device for CNS repair.

Tubular scaffolds which incorporate a variety of micro- and nanotopographies have a wide application potential in tissue engineering especially for the repair of spinal cord injury (SCI). We aim to produce metabolically active differentiated tissues within such tubes, as it is crucially important to evaluate the biological performance of the three-dimensional (3D) scaffold and optimize the bioprocesses for tissue culture. Because of the complex 3D configuration and the presence of various topographies, it is rarely possible to observe and analyze cells within such scaffolds in situ.

Poly(N-acryloylmorpholine): a simple hydrogel system for temporal and spatial control over cell adhesion.

N-acryloylmorpholine (NAM) was photo-polymerized to produce the homopolymer poly(N-acryloylmorpholine) (PNAM). PNAM behaves as a physical hydrogel in aqueous solvents, doubling its dry weight over a 2 h period before undergoing dissolution following a second order exponential decay profile. In vitro cellular experiments using mouse myoblasts showed that PNAM acts as an effective spatial cell barrier for 38 h, with slow migration of cells into the PNAM area occurring between 45 and 73 h after cell seeding.

Osteogenesis of mesenchymal stem cells by nanoscale mechanotransduction.

It is likely that mesenchymal stem cells will find use in many autologous regenerative therapies. However, our ability to control cell stem growth and differentiation is presently limited, and this is a major hurdle to the clinical use of these multipotent cells especially when considering the desire not to use soluble factors or complex media formulations in culture. Also, the large number of cells required to be clinically useful is currently a hurdle to using materials-based (stiffness, chemistry, nanotopography, etc.

Influence of variable substrate geometry on wettability and cellular responses.

In this report, we evaluate the impact of a systematic change to the extracellular environment on cell morphology and functionality by combining the inherent properties of biocompatible polymers such as polydimethylsiloxane and polycaprolactone with a specific surface response. By microstructuring pillars and pits on the substrates, varying spacing and height of the structures, we investigate the role of topography in fibroblast cell adhesion and viability. The change of wetting behaviour was tailored and evaluated in terms of contact angle measurements.