Investigating Internalization of Reporter-Protein-Functionalized Polyhedrin Particles by Brain Immune Cells.

Achieving sustained drug delivery to the central nervous system (CNS) is a major challenge for neurological injury and disease, and various delivery vehicles are being developed to achieve this. Self-assembling polyhedrin crystals (POlyhedrin Delivery System; PODS) are being exploited for the delivery of therapeutic protein cargo, with demonstrated efficacy in vivo. However, to establish the utility of PODS for neural applications, their handling by neural immune cells (microglia) must be documented, as these cells process and degrade many biomaterials, often preventing therapeutic efficacy.

A requirement for astrocyte IPR2 signaling for whisker experience-dependent depression and homeostatic upregulation in the mouse barrel cortex.

Changes to sensory experience result in plasticity of synapses in the cortex. This experience-dependent plasticity (EDP) is a fundamental property of the brain. Yet, while much is known about neuronal roles in EDP, very little is known about the role of astrocytes.

In vitro model of traumatic brain injury to screen neuro-regenerative biomaterials.

Penetrating traumatic brain injury (pTBI) causes serious neurological deficits with no clinical regenerative therapies currently available. Tissue engineering strategies using biomaterial-based 'structural bridges' offer high potential to promote neural regeneration post-injury. This includes surgical grade materials which can be repurposed as biological scaffolds to overcome challenges associated with long approval processes and scaleup for human application.

Physico-Chemically Distinct Nanomaterials Synthesized from Derivates of a Poly(Anhydride) Diversify the Spectrum of Loadable Antibiotics.

Recent advances in the field of nanotechnology such as nanoencapsulation offer new biomedical applications, potentially increasing the scope and efficacy of therapeutic drug delivery. In addition, the discovery and development of novel biocompatible polymers increases the versatility of these encapsulating nanostructures, enabling chemical properties of the cargo and vehicle to be adapted to specific physiological requirements. Here, we evaluate the capacity of various polymeric nanostructures to encapsulate various antibiotics of different classes, with differing chemical structure.

The Influence of Nicotinamide on Health and Disease in the Central Nervous System.

Nicotinamide, the amide form of vitamin B (niacin), has long been associated with neuronal development, survival, and function in the central nervous system (CNS), being implicated in both neuronal death and neuroprotection. Here, we summarise a body of research investigating the role of nicotinamide in neuronal health within the CNS, with a focus on studies that have shown a neuroprotective effect. Nicotinamide appears to play a role in protecting neurons from traumatic injury, ischaemia, and stroke, as well as being implicated in 3 key neurodegenerative conditions: Alzheimer's, Parkinson's, and Huntington's diseases.

Endocytotic potential governs magnetic particle loading in dividing neural cells: studying modes of particle inheritance.

Aim: To achieve high and sustained magnetic particle loading in a proliferative and endocytotically active neural transplant population (astrocytes) through tailored magnetite content in polymeric iron oxide particles.

Materials & Methods: MPs of varying magnetite content were applied to primary-derived rat cortical astrocytes ± static/oscillating magnetic fields to assess labeling efficiency and safety.

Results: Higher magnetite content particles display high but safe accumulation in astrocytes, with longer-term label retention versus lower/no magnetite content particles.

'Stealth' nanoparticles evade neural immune cells but also evade major brain cell populations: Implications for PEG-based neurotherapeutics.

Surface engineering to control cell behavior is of high interest across the chemical engineering, drug delivery and biomaterial communities. Defined chemical strategies are necessary to tailor nanoscale protein interactions/adsorption, enabling control of cell behaviors for development of novel therapeutic strategies. Nanoparticle-based therapies benefit from such strategies but particle targeting to sites of neurological injury remains challenging due to circulatory immune clearance.

The early career researcher's toolkit: translating tissue engineering, regenerative medicine and cell therapy products.

Although the importance of translation for the development of tissue engineering, regenerative medicine and cell-based therapies is widely recognized, the process of translation is less well understood. This is particularly the case among some early career researchers who may not appreciate the intricacies of translational research or make decisions early in development which later hinders effective translation. Based on our own research and experiences as early career researchers involved in tissue engineering and regenerative medicine translation, we discuss common pitfalls associated with translational research, providing practical solutions and important considerations which will aid process and product development.

Development of a nanomaterial bio-screening platform for neurological applications.

Nanoparticle platforms are being intensively investigated for neurological applications. Current biological models used to identify clinically relevant materials have major limitations, e.g.

Magnetic nanoparticles for oligodendrocyte precursor cell transplantation therapies: progress and challenges.

Oligodendrocyte precursor cells (OPCs) have shown high promise as a transplant population to promote regeneration in the central nervous system, specifically, for the production of myelin - the protective sheath around nerve fibers. While clinical trials for these cells have commenced in some areas, there are currently key barriers to the translation of neural cell therapies. These include the ability to (a) image transplant populations in vivo; (b) genetically engineer transplant cells to augment their repair potential; and (c) safely target cells to sites of pathology.

Identifying the cellular targets of drug action in the central nervous system following corticosteroid therapy.

Corticosteroid (CS) therapy is used widely in the treatment of a range of pathologies, but can delay production of myelin, the insulating sheath around central nervous system nerve fibers. The cellular targets of CS action are not fully understood, that is, "direct" action on cells involved in myelin genesis [oligodendrocytes and their progenitors the oligodendrocyte precursor cells (OPCs)] versus "indirect" action on other neural cells. We evaluated the effects of the widely used CS dexamethasone (DEX) on purified OPCs and oligodendrocytes, employing complementary histological and transcriptional analyses.

Differences in magnetic particle uptake by CNS neuroglial subclasses: implications for neural tissue engineering.

Aim: To analyze magnetic particle uptake and intracellular processing by the four main non-neuronal subclasses of the CNS: oligodendrocyte precursor cells; oligodendrocytes; astrocytes; and microglia.

Materials & Methods: Magnetic particle uptake and processing were studied in rat oligodendrocyte precursor cells and oligodendrocytes using fluorescence and transmission electron microscopy, and the results collated with previous data from rat microglia and astrocyte studies. All cells were derived from primary mixed glial cultures.

Magnetic nanoparticle-mediated gene transfer to oligodendrocyte precursor cell transplant populations is enhanced by magnetofection strategies.

This study has tested the feasibility of using physical delivery methods, employing static and oscillating field "magnetofection" techniques, to enhance magnetic nanoparticle-mediated gene transfer to rat oligodendrocyte precursor cells derived for transplantation therapies. These cells are a major transplant population to mediate repair of damage as occurs in spinal cord injury and neurological diseases such as multiple sclerosis. We show for the first time that magnetic nanoparticles mediate effective transfer of reporter and therapeutic genes to oligodendrocyte precursors; transfection efficacy was significantly enhanced by applied static or oscillating magnetic fields, the latter using an oscillating array employing high-gradient NdFeB magnets.

Magnetic nanoparticle labeling of astrocytes derived for neural transplantation.

Astrocytes are a major transplant cell population to promote neural repair in a range of pathological conditions. In this context, the development of robust methods to label neural transplant populations (for subsequent detection and cell tracking in vivo) is key for translational applications. Magnetic iron oxide nanoparticles (MNP)-based vector systems offer a range of advantages for neural cell transplantation, notably, as contrast agents for magnetic resonance imaging, which allows for MNP-labeled cells to be detected using minimally invasive methods.