The spectrum of Ih ice using terahertz time-domain spectroscopy.

Here, we report the frequency-dependent spectrum of ice Ih in the range of 0.2-2 THz. We confirm the presence of a feature that blue-shifts from around 1.55-1.65 THz with a decreasing temperature from 260 to 160 K. There is also a change in the trend of the refractive index of ice corresponding to a dispersion, which is also around 1.6 THz. The features are reproduced in data acquired with three commercial terahertz time-domain spectrometers. Computer-simulated spectra assign the feature to lattice translations perpendicular to the 110 and 1̄10 planes of the ice Ih crystal. The feature's existence should be recognized in the terahertz measurements of frozen aqueous solution samples to avoid false interpretations.

The psychophysiology of music-based interventions and the experience of pain.

In modern times there is increasing acceptance that music-based interventions are useful aids in the clinical treatment of a range of neurological and psychiatric conditions, including helping to reduce the perception of pain. Indeed, the belief that music, whether listening or performing, can alter human pain experiences has a long history, dating back to the ancient Greeks, and its potential healing properties have long been appreciated by indigenous cultures around the world. The subjective experience of acute or chronic pain is complex, influenced by many intersecting physiological and psychological factors, and it is therefore to be expected that the impact of music therapy on the pain experience may vary from one situation to another, and from one person to another. Where pain persists and becomes chronic, aberrant central processing is a key feature associated with the ongoing pain experience. Nonetheless, beneficial effects of exposure to music on pain relief have been reported across a wide range of acute and chronic conditions, and it has been shown to be effective in neonates, children and adults. In this comprehensive review we examine the various neurochemical, physiological and psychological factors that underpin the impact of music on the pain experience, factors that potentially operate at many levels - the periphery, spinal cord, brainstem, limbic system and multiple areas of cerebral cortex. We discuss the extent to which these factors, individually or in combination, influence how music affects both the quality and intensity of pain, noting that there remains controversy about the respective roles that diverse central and peripheral processes play in this experience. Better understanding of the mechanisms that underlie music's impact on pain perception together with insights into central processing of pain should aid in developing more effective synergistic approaches when music therapy is combined with clinical treatments. The ubiquitous nature of music also facilitates application from the therapeutic environment into daily life, for ongoing individual and social benefit.

Hydration water drives the self-assembly of guanosine monophosphate.

Guanosine monophosphate (GMP) is a nucleotide that can self-assemble in aqueous solution under certain conditions. An understanding of the process at the molecular level is an essential step to comprehend the involvement of DNA substructures in transcription and replication, as well as their relationship to genetic diseases such as cancer. We present the temperature-dependent terahertz (1.5-12 THz, 50-400 cm-1) absorptivity spectra of aqueous Na2 GMP solution in comparison with the aqueous solutions of other RNA nucleotides. Distinct absorption features were observed in the spectrum of GMP, which we attribute to the intramolecular modes of the self-assemblies (i.e., G-complexes) that, at 1 M, start to form at 313 K and below. Changes in broad-band features of the terahertz spectrum were also observed, which we associate with the release of hydration water in the temperature-dependent formation of guanine quadruplexes. Using a state-of-the-art THz calorimetry approach correlating spectroscopic to thermodynamic changes, we propose a molecular mechanism of hydrophilic hydration driving GMP self-assembly as a function of temperature. The free energy contribution of hydrophilic hydration is shown as a decisive factor in guanine-quadruplex formation. Our findings spotlight the role of hydration in the formation of macromolecular structures and suggest the potential of hydration tuning for regulating DNA transcription and replication.

Neuronal Replenishment via Hydrogel-Rationed Delivery of Reprogramming Factors.

The central nervous system's limited capacity for regeneration often leads to permanent neuronal loss following injury. Reprogramming resident reactive astrocytes into induced neurons at the site of injury is a promising strategy for neural repair, but challenges persist in stabilizing and accurately targeting viral vectors for transgene expression. In this study, we employed a bioinspired self-assembling peptide (SAP) hydrogel for the precise and controlled release of a hybrid adeno-associated virus (AAV) vector, AAVDJ, carrying the NeuroD1 neural reprogramming transgene. This method effectively mitigates the issues of high viral dosage at the target site, off-target delivery, and immunogenic reactions, enhancing the vector's targeting and reprogramming efficiency. In vitro, this vector successfully induced neuron formation, as confirmed by morphological, histochemical, and electrophysiological analyses. In vivo, SAP-mediated delivery of AAVDJ-NeuroD1 facilitated the trans-differentiation of reactive host astrocytes into induced neurons, concurrently reducing glial scarring. Our findings introduce a safe and effective method for treating central nervous system injuries, marking a significant advancement in regenerative neuroscience.

Calming the Nerves via the Immune Instructive Physiochemical Properties of Self-Assembling Peptide Hydrogels.

Current therapies for the devastating damage caused by traumatic brain injuries (TBI) are limited. This is in part due to poor drug efficacy to modulate neuroinflammation, angiogenesis and/or promoting neuroprotection and is the combined result of challenges in getting drugs across the blood brain barrier, in a targeted approach. The negative impact of the injured extracellular matrix (ECM) has been identified as a factor in restricting post-injury plasticity of residual neurons and is shown to reduce the functional integration of grafted cells. Therefore, new strategies are needed to manipulate the extracellular environment at the subacute phase to enhance brain regeneration. In this review, potential strategies are to be discussed for the treatment of TBI by using self-assembling peptide (SAP) hydrogels, fabricated via the rational design of supramolecular peptide scaffolds, as an artificial ECM which under the appropriate conditions yields a supramolecular hydrogel. Sequence selection of the peptides allows the tuning of these hydrogels' physical and biochemical properties such as charge, hydrophobicity, cell adhesiveness, stiffness, factor presentation, degradation profile and responsiveness to (external) stimuli. This review aims to facilitate the development of more intelligent biomaterials in the future to satisfy the parameters, requirements, and opportunities for the effective treatment of TBI.

The role of epigenetic changes in the pathology and treatment of inherited retinal diseases.

Elucidation of the cellular changes that occur in degenerating photoreceptors of people with inherited retinal diseases (IRDs) has been a focus for many research teams, leading to numerous theories on how these changes affect the cell death process. What is clearly emerging from these studies is that there are common denominators across multiple models of IRD, regardless of the underlying genetic mutation. These common markers could open avenues for broad neuroprotective therapeutics to prevent photoreceptor loss and preserve functional vision. In recent years, the role of epigenetic modifications contributing to the pathology of IRDs has been a particular point of interest, due to many studies noting changes in these epigenetic modifications, which coincide with photoreceptor cell death. This review will discuss the two broad categories of epigenetic changes, DNA methylation and histone modifications, that have received particular attention in IRD models. We will review the altered epigenetic regulatory events that are believed to contribute to cell death in IRDs and discuss the therapeutic potential of targeting these alterations.

Compensatory Cone-Mediated Mechanisms in Inherited Retinal Degeneration Mouse Models: A Functional and Gene Expression Analysis.

The retina undergoes compensatory changes in response to progressive photoreceptor loss/dysfunction; however, studies of inherited retinal diseases (IRDs) often lack a temporal connection between gene expression and visual function. Here, we used three mouse models of IRD - Cnga3-/-, Pde6ccpfl1, and Rd1 - to investigate over time the effect of photoreceptor degeneration, particularly cones, on visual function and gene expression. Changes to gene expression include increases in cell survival and cell death genes in Pde6ccpfl1 before significant cell loss, as well as an increase in cone-specific genes in the Rd1 at the peak of rod death. We show that Cnga3-/- and Pde6ccpfl1 mice maintained photopic visual acuity via optomotor responses, despite no recordable cone electroretinogram (ERG), while functional measures and photoreceptors loss were correlated in Rd1 mice. There were also significant changes to oscillatory potentials (OPs) in Cnga3-/- and Pde6ccpfl1, implying an effect on inner retinal cells as a result of cone degeneration. These results indicate a potentially malleable retinal environment following cone degeneration; however, further investigation is needed to elucidate how these changes compensate for the loss of cone function.

Differentiation and functional connectivity of fetal tectal transplants.

Data from studies analyzing the differentiation and functional connectivity of embryonic neural tissue grafted into the mammalian nervous system has led to the clinical testing of the fetal graft approach in patients with neurodegenerative disease. While some success has been achieved, ethical concerns have led to a search for alternative therapeutic strategies, mostly exploring the use of neural precursors or neurons derived from pluripotent stem cells to replace damaged host neurons and restore lost circuitries. These more recent studies address questions of graft viability, differentiation, and connectivity similar to those posed by researchers in earlier fetal transplant work, thus reviews of the fetal graft literature may inform and help guide ongoing research in the stem cell/organoid field. This brief review describes some key observations from research into the transplantation of neural tissue into the rat visual system, focusing on grafts of the fetal superior colliculus (tectal grafts) into neonatal or adult hosts. In neonate hosts, grafts quickly develop connections with the underlying host midbrain and attain a morphology typical of mature grafts by about 2 weeks. Grafts consistently contain numerous localized regions which, based on neurofibrillar staining, neuronal morphology (Golgi), neurochemistry, receptor expression, and glial architecture, are homologous to the stratum griseum superficiale of normal superior colliculus. These localized "patches" are also seen after explant culture and when donor tectal tissue is dissociated and reaggregated prior to transplantation. In almost all circumstances, host retinal innervation is restricted to these localized patches, but only those that are located adjacent to the graft surface. Synapses are formed and there is evidence of functional drive. The only exception occurs when Schwann cells are added to dissociated tecta prior to reaggregation. In these co-grafts, the peripheral glia appear to compete with local target factors and host retinal ingrowth is more widespread. Other afferent systems (e.g., host cortex, serotonin) show different patterns of innervation. The host cortical input originates more from extrastriate regions and establishes functional excitatory synapses with grafted neurons. Finally, when grafted into optic tract lesions in adult rat hosts, spontaneously regrowing host retinal axons retain the capacity to selectively innervate the localized patches in embryonic tectal grafts, showing that the specific affinities between adult retinal axons and their targets are not lost during regeneration. While the research described here provides some pertinent information about development and plasticity in visual pathways, a more general aim is to highlight how the review of the extensive fetal graft literature may aid in an appreciation of the positive (and negative) factors that influence survival, differentiation, connectivity and functionality of engineered cells and organoids transplanted into the central nervous system.

Offline Parietal Intermittent Theta Burst Stimulation or Alpha Frequency Transcranial Alternating Current Stimulation Has No Effect on Visuospatial or Temporal Attention.

Non-invasive brain stimulation is a growing field with potentially wide-ranging clinical and basic science applications due to its ability to transiently and safely change brain excitability. In this study we include two types of stimulation: repetitive transcranial magnetic stimulation (rTMS) and transcranial alternating current stimulation (tACS). Single session stimulations with either technique have previously been reported to induce changes in attention. To better understand and compare the effectiveness of each technique and the basis of their effects on cognition we assessed changes to both temporal and visuospatial attention using an attentional blink task and a line bisection task following offline stimulation with an intermittent theta burst (iTBS) rTMS protocol or 10 Hz tACS. Additionally, we included a novel rTMS stimulation technique, low-intensity (LI-)rTMS, also using an iTBS protocol, which uses stimulation intensities an order of magnitude below conventional rTMS. Animal models show that low-intensity rTMS modulates cortical excitability despite sub-action potential threshold stimulation. Stimulation was delivered in healthy participants over the right posterior parietal cortex (rPPC) using a within-subjects design (n = 24). Analyses showed no evidence for an effect of any stimulation technique on spatial biases in the line bisection task or on magnitude of the attentional blink. Our results suggests that rTMS and LI-rTMS using iTBS protocol and 10 Hz tACS over rPPC do not modulate performance in tasks assessing visuospatial or temporal attention.

Ultrahigh Carrier Mobilities in Ferroelectric Domain Wall Corbino Cones at Room Temperature.

Recently, electrically conducting heterointerfaces between dissimilar band insulators (such as lanthanum aluminate and strontium titanate) have attracted considerable research interest. Charge transport and fundamental aspects of conduction have been thoroughly explored. Perhaps surprisingly, similar studies on conceptually much simpler conducting homointerfaces, such as domain walls, are not nearly so well developed. Addressing this disparity, magnetoresistance is herein reported in approximately conical 180° charged domain walls, in partially switched ferroelectric thin-film single-crystal lithium niobate. This system is ideal for such measurements: first, the conductivity difference between domains and domain walls is unusually large (a factor of 1013 ) and hence currents driven through the thin film, between planar top and bottom electrodes, are overwhelmingly channeled along the walls; second, when electrical contact is made to the top and bottom of the domain walls and a magnetic field is applied along their cone axes, then the test geometry mirrors that of a Corbino disk: a textbook arrangement for geometric magnetoresistance measurement. Data imply carriers with extremely high room-temperature Hall mobilities of up to ≈3700 cm2 V-1 s-1 . This is an unparalleled value for oxide interfaces (and for bulk oxides) comparable to mobilities in other systems seen at cryogenic, rather than at room, temperature.

Changing Fate: Reprogramming Cells via Engineered Nanoscale Delivery Materials.

The incorporation of nanotechnology in regenerative medicine is at the nexus of fundamental innovations and early-stage breakthroughs, enabling exciting biomedical advances. One of the most exciting recent developments is the use of nanoscale constructs to influence the fate of cells, which are the basic building blocks of healthy function. Appropriate cell types can be effectively manipulated by direct cell reprogramming; a robust technique to manipulate cellular function and fate, underpinning burgeoning advances in drug delivery systems, regenerative medicine, and disease remodeling. Individual transcription factors, or combinations thereof, can be introduced into cells using both viral and nonviral delivery systems. Existing approaches have inherent limitations. Viral-based tools include issues of viral integration into the genome of the cells, the propensity for uncontrollable silencing, reduced copy potential and cell specificity, and neutralization via the immune response. Current nonviral cell reprogramming tools generally suffer from inferior expression efficiency. Nanomaterials are increasingly being explored to address these challenges and improve the efficacy of both viral and nonviral delivery because of their unique properties such as small size and high surface area. This review presents the state-of-the-art research in cell reprogramming, focused on recent breakthroughs in the deployment of nanomaterials as cell reprogramming delivery tools.

Manipulating the Level of Sensorimotor Stimulation during LI-rTMS Can Improve Visual Circuit Reorganisation in Adult Ephrin-A2A5-/- Mice.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that has the potential to treat a variety of neurologic and psychiatric disorders. The extent of rTMS-induced neuroplasticity may be dependent on a subject's brain state at the time of stimulation. Chronic low intensity rTMS (LI-rTMS) has previously been shown to induce beneficial structural and functional reorganisation within the abnormal visual circuits of ephrin-A2A5-/- mice in ambient lighting. Here, we administered chronic LI-rTMS in adult ephrin-A2A5-/- mice either in a dark environment or concurrently with voluntary locomotion. One day after the last stimulation session, optokinetic responses were assessed and fluorescent tracers were injected to map corticotectal and geniculocortical projections. We found that LI-rTMS in either treatment condition refined the geniculocortical map. Corticotectal projections were improved in locomotion+LI-rTMS subjects, but not in dark + LI-rTMS and sham groups. Visuomotor behaviour was not improved in any condition. Our results suggest that the beneficial reorganisation of abnormal visual circuits by rTMS can be significantly influenced by simultaneous, ambient visual input and is enhanced by concomitant physical exercise. Furthermore, the observed pathway-specific effects suggest that regional molecular changes and/or the relative proximity of terminals to the induced electric fields influence the outcomes of LI-rTMS on abnormal circuitry.

Primary and Secondary Cone Cell Death Mechanisms in Inherited Retinal Diseases and Potential Treatment Options.

Inherited retinal diseases (IRDs) are a leading cause of blindness. To date, 260 disease-causing genes have been identified, but there is currently a lack of available and effective treatment options. Cone photoreceptors are responsible for daylight vision but are highly susceptible to disease progression, the loss of cone-mediated vision having the highest impact on the quality of life of IRD patients. Cone degeneration can occur either directly via mutations in cone-specific genes (primary cone death), or indirectly via the primary degeneration of rods followed by subsequent degeneration of cones (secondary cone death). How cones degenerate as a result of pathological mutations remains unclear, hindering the development of effective therapies for IRDs. This review aims to highlight similarities and differences between primary and secondary cone cell death in inherited retinal diseases in order to better define cone death mechanisms and further identify potential treatment options.

Effects of amyloid precursor protein peptide APP96-110, alone or with human mesenchymal stromal cells, on recovery after spinal cord injury.

Delivery of a peptide (APP96-110), derived from amyloid precursor protein (APP), has been shown to elicit neuroprotective effects following cerebral stroke and traumatic brain injury. In this study, the effect of APP96-110 or a mutant version of this peptide (mAPP96-110) was assessed following moderate (200 kdyn, (2 N)) thoracic contusive spinal cord injury (SCI) in adult Nude rats. Animals received a single tail vein injection of APP96-110 or mAPP96-110 at 30 minutes post-SCI and were then assessed for functional improvements over the next 8 weeks. A cohort of animals also received transplants of either viable or non-viable human mesenchymal stromal cells (hMSCs) into the SC lesion site at one week post-injury to assess the effect of combining intravenous APP96-110 delivery with hMSC treatment. Rats were perfused 8 weeks post-SCI and longitudinal sections of spinal cord analyzed for a number of factors including hMSC viability, cyst size, axonal regrowth, glial reactivity and macrophage activation. Analysis of sensorimotor function revealed occasional significant differences between groups using Ladderwalk or Ratwalk tests, however there were no consistent improvements in functional outcome after any of the treatments. mAPP96-110 alone, and APP96-110 in combination with both viable and non-viable hMSCs significantly reduced cyst size compared to SCI alone. Combined treatments with donor hMSCs also significantly increased ßIII tubulin+, glial fibrillary acidic protein (GFAP+) and laminin+ expression, and decreased ED1+ expression in tissues. This preliminary study demonstrates that intravenous delivery of APP96-110 peptide has selective, modest neuroprotective effects following SCI, which may be enhanced when combined with hMSC transplantation. However, the effects are less pronounced and less consistent compared to the protective morphological and cognitive impact that this same peptide has on neuronal survival and behaviour after stroke and traumatic brain injury. Thus while the efficacy of a particular therapeutic approach in one CNS injury model may provide justification for its use in other neurotrauma models, similar outcomes may not necessarily occur and more targeted approaches suited to location and severity are required. All animal experiments were approved by The University of Western Australia Animal Ethics Committee (RA3/100/1460) on April 12, 2016.

Age Related Response of Neonatal Rat Retinal Ganglion Cells to Reduced TrkB Signaling in vitro and in vivo.

During development of retinofugal pathways there is naturally occurring cell death of at least 50% of retinal ganglion cells (RGCs). In rats, RGC death occurs over a protracted pre- and early postnatal period, the timing linked to the onset of axonal ingrowth into central visual targets. Gene expression studies suggest that developing RGCs switch from local to target-derived neurotrophic support during this innervation phase. Here we investigated, in vitro and in vivo, how RGC birthdate affects the timing of the transition from intra-retinal to target-derived neurotrophin dependence. RGCs were pre-labeled with 5-Bromo-2'-Deoxyuridine (BrdU) at embryonic (E) day 15 or 18. For in vitro studies, RGCs were purified from postnatal day 1 (P1) rat pups and cultured with or without: (i) brain derived neurotrophic factor (BDNF), (ii) blocking antibodies to BDNF and neurotrophin 4/5 (NT-4/5), or (iii) a tropomyosin receptor kinase B fusion protein (TrkB-Fc). RGC viability was quantified 24 and 48 h after plating. By 48 h, the survival of purified ßIII-tubulin immunopositive E15 but not E18 RGCs was dependent on addition of BDNF to the culture medium. For E18 RGCs, in the absence of exogenous BDNF, addition of blocking antibodies or TrkB-Fc reduced RGC viability at both 24 and 48 h by 25-40%. While this decrease was not significant due to high variance, importantly, each blocking method also consistently reduced complex process expression in surviving RGCs. In vivo, survival of BrdU and Brn3a co-labeled E15 or E18 RGCs was quantified in rats 24 h after P1 or P5 injection into the eye or contralateral superior colliculus (SC) of BDNF and NT-4/5 antibodies, or serum vehicle. The density of E15 RGCs 24 h after P1 or P5 injection of blocking antibodies was reduced after SC but not intraretinal injection. Antibody injections into either site had little obvious impact on viability of the substantially smaller population of E18 RGCs. In summary, most early postnatal RGC death in the rat involves the elimination of early-born RGCs with their survival primarily dependent upon the availability of target derived BDNF during this time. In contrast, late-born RGC survival may be influenced by additional factors, suggesting an association between RGC birthdate and developmental death mechanisms.

Anomalous Motion of Charged Domain Walls and Associated Negative Capacitance in Copper-Chlorine Boracite.

During switching, the microstructure of a ferroelectric normally adapts to align internal dipoles with external electric fields. Favorably oriented dipolar regions (domains) grow at the expense of those in unfavorable orientations and this is manifested in a predictable field-induced motion of the walls that separate one domain from the next. Here, the discovery that specific charged 90°domain walls in copper-chlorine boracite move in the opposite direction to that expected, increasing the size of the domain in which polarization is anti-aligned with the applied field, is reported. Polarization-field (P-E) hysteresis loops, inferred from optical imaging, show negative gradients and non-transient negative capacitance, throughout the P-E cycle. Switching currents (generated by the relative motion between domain walls and sensing electrodes) confirm this, insofar as their signs are opposite to those expected conventionally. For any given bias, the integrated switching charge due to this anomalous wall motion is directly proportional to time, indicating that the magnitude of the negative capacitance component should be inversely related to frequency. This passes Jonscher's test for the misinterpretation of positive inductance and gives confidence that field-induced motion of these specific charged domain walls generates a measurable negative capacitance contribution to the overall dielectric response.

Low intensity repetitive magnetic stimulation reduces expression of genes related to inflammation and calcium signalling in cultured mouse cortical astrocytes.

Repetitive transcranial magnetic stimulation (rTMS) is a form of non-invasive brain stimulation frequently used to induce neuroplasticity in the brain. Even at low intensities, rTMS has been shown to modulate aspects of neuronal plasticity such as motor learning and structural reorganisation of neural tissue. However, the impact of low intensity rTMS on glial cells such as astrocytes remains largely unknown. This study investigated changes in RNA (qPCR array: 125 selected genes) and protein levels (immunofluorescence) in cultured mouse astrocytes following a single session of low intensity repetitive magnetic stimulation (LI-rMS - 18 mT). Purified neonatal cortical astrocyte cultures were stimulated with either 1Hz (600 pulses), 10Hz (600 or 6000 pulses) or sham (0 pulses) LI-rMS, followed by RNA extraction at 5 h post-stimulation, or fixation at either 5 or 24-h post-stimulation. LI-rMS resulted in a two-to-four-fold downregulation of mRNA transcripts related to calcium signalling (Stim1 and Orai3), inflammatory molecules (Icam1) and neural plasticity (Ncam1). 10Hz reduced expression of Stim1, Orai3, Kcnmb4, and Ncam1 mRNA, whereas 1Hz reduced expression of Icam1 mRNA and signalling-related genes. Protein levels followed a similar pattern for 10Hz rMS, with a significant reduction of STIM1, ORAI3, KCNMB4, and NCAM1 protein compared to sham, but 1Hz increased STIM1 and ORAI3 protein levels relative to sham. These findings demonstrate the ability of 1Hz and 10Hz LI-rMS to modulate specific aspects of astrocytic phenotype, potentially contributing to the known effects of low intensity rTMS on excitability and neuroplasticity.

Peptide Hydrogel Scaffold for Mesenchymal Precursor Cells Implanted to Injured Adult Rat Spinal Cord.

A unique, biomimetic self-assembling peptide (SAP) hydrogel, Fmoc-DIKVAV, has been shown to be a suitable cell and drug delivery system in the injured brain. In this study, we assessed its utility in adult Fischer 344 (F344) rats as a stabilizing scaffold and vehicle for grafted cells after mild thoracic (thoracic level 10 [T10]) contusion spinal cord injury (SCI). Treatments were as follows: Fmoc-DIKVAV alone, Fmoc-DIKVAV containing viable or nonviable rat mesenchymal precursor cells (rMPCs), and rMPCs alone. The majority of post-SCI treatments were administered at 11-15 days (mean 13.5 days) and the results then compared to SCI-only control (no treatment) rats. Postinjury behavior was quantified using open field locomotion (BBB) and LadderWalk analysis. After perfusion at 8 weeks, longitudinal spinal cord sections were immunostained with a panel of antibodies. Qualitatively, in the SAP-only treatment group, implanted gels contained regenerate axons as well as astrocytic, immune cell, and extracellular matrix (ECM) component profiles. Grafts of Fmoc-DIKVAV plus viable or nonviable rMPCs also contained numerous macrophages/microglia and ECM components, but astrocytes were generally confined to implant margins, and axons were rare. Quantitative analysis showed that, while average cyst size was reduced in all experimental groups, the decrease compared to SCI-only controls was only significant in the SAP and rMPC treatment groups. There was gradual improvement in functionality after SCI, but a consistent trend was only seen between the rMPC treatment group and SCI-only controls. In summary, after contusion SCI, implantation of Fmoc-DIKVAV hydrogel provided a favorable microenvironment for cellular infiltration and axonal regrowth, a supportive role that unexpectedly appeared to be compromised by prior inclusion of rMPCs into the gel matrix. Impact statement The self-assembling peptide hydrogel, Fmoc-DIKVAV, is a biomimetic scaffold that is an effective cell and drug delivery system in the injured brain. We examined whether this hydrogel, alone or combined with mesenchymal precursor cells, was also able to stabilise spinal cord tissue after thoracic contusion injury and improve morphological and behavioral outcomes. While improved functionality was not consistently seen, there was reduced cyst size and increased tissue sparing in some groups. There was regenerative axonal growth into hydrogels, but only in initially cell-free implants. This type of polymer is a suitable candidate for further testing in spinal cord injury models.

Is Viral Vector Gene Delivery More Effective Using Biomaterials?

Gene delivery has been extensively investigated for introducing foreign genetic material into cells to promote expression of therapeutic proteins or to silence relevant genes. This approach can regulate genetic or epigenetic disorders, offering an attractive alternative to pharmacological therapy or invasive protein delivery options. However, the exciting potential of viral gene therapy has yet to be fully realized, with a number of clinical trials failing to deliver optimal therapeutic outcomes. Reasons for this include difficulty in achieving localized delivery, and subsequently lower efficacy at the target site, as well as poor or inconsistent transduction efficiency. Thus, ongoing efforts are focused on improving local viral delivery and enhancing its efficiency. Recently, biomaterials have been exploited as an option for more controlled, targeted and programmable gene delivery. There is a growing body of literature demonstrating the efficacy of biomaterials and their potential advantages over other delivery strategies. This review explores current limitations of gene delivery and the progress of biomaterial-mediated gene delivery. The combination of biomaterials and gene vectors holds the potential to surmount major challenges, including the uncontrolled release of viral vectors with random delivery duration, poorly localized viral delivery with associated off-target effects, limited viral tropism, and immune safety concerns.