Biology subjects

Dervan, A.

Publications and source records attributed to Dervan, A..

5 recordsLinked to original sources

bioRxiv2025

Scaffold-mediated miRNA-155 inhibition promotes regenerative macrophage polarisation leading to anti-inflammatory, angiogenic, and neurogenic responses for wound healing

Chronic wounds represent a significant clinical challenge due to persistent inflammation and impaired nerve regeneration, both of which delay healing. Conventional treatments often yield limited success and inconsistent outcomes, especially in complex and recurring wounds. Combinatorial strategies that integrate biomaterial scaffolds with gene delivery offer a promising approach to promote tissue repair. MicroRNAs (miRNAs), particularly miRNA-155, have emerged as crucial regulators of wound healing. MiRNA-155 is highly expressed in inflammatory conditions and plays a key role in macrophage activation, polarisation, and nerve regeneration. In this context, this study introduces a miRNA-155 inhibitor-activated scaffold designed to modulate the chronic wound environment by inhibiting miRNA-155. MiRNA-155 inhibitor complexed GET nanoparticles were characterised and incorporated into collagen-glycosaminoglycan (CG) scaffolds. These supported dermal fibroblast and endothelial cell growth while enabling controlled inhibitor release. Scaffold-mediated miRNA-155 inhibition in both non-polarised (M0) and pro-inflammatory (M1) macrophages promoted anti-inflammatory (M2) polarisation. Macrophage secretome analysis showed reduced inflammatory cytokines and increased angiogenic growth factor secretion in both conditions. The regenerative potential of the miRNA-i-activated scaffold via macrophage polarisation was validated through inflammatory and angiogenic functional assays with endothelial cells. In parallel, scaffold-mediated miRNA-155 delivery to dorsal root ganglia (DRG) promoted neurogenic outcomes through enhanced axonal regrowth, essential for the synergistic repair of chronic wounds across the skin-nerve axis. In vivo implantation of miRNA-155 inhibitor-activated scaffolds in chicks demonstrated successful integration without disrupting vascular network formation. Collectively, these findings establish the miRNA-155 inhibitor-activated scaffold as a regenerative platform with anti-inflammatory, pro-angiogenic, and neurogenic outcomes, offering a multifaceted solution for chronic wound healing applications. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=117 SRC="FIGDIR/small/682055v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@1c6a6b6org.highwire.dtl.DTLVardef@eb04f9org.highwire.dtl.DTLVardef@1937f15org.highwire.dtl.DTLVardef@7c70d3_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

PolyGraph - Flexible, Biocompatible & Electrically Optimised Graphene-Polymer Composites for Next-Generation Neural Interfaces

Neural interfacing materials must deliver exceptional electrochemical performance, while integrating safely with the central nervous system. In this study we develop PolyGraph, a flexible, conductive, and biocompatible graphene-polycaprolactone (PCL) nanocomposite designed to strike this balance, which enables fabrication of conformable multichannel microelectrode arrays. Optimised liquid-phase exfoliation produces conductive, biocompatible PVP-stabilised graphene nanosheets, which are incorporated into PCL to form flexible, processable composites - PolyGraph. This material demonstrates bio- and immuno-compatibility with sensitive primary and iPSC-derived neuronal and glial cells. PolyGraph achieves low impedance ([~]1.6 {Omega} cm2 @ 1 kHz) and high charge injection capacity (11.7 mC/cm2 for a 100 ms pulse), enhanced by NaOH surface roughening and AuPd coating. Leveraging their processability, PolyGraph composites are fabricated into flexible, individually isolated microneedle electrode arrays with biomimetic soft hyaluronic acid backings. These arrays demonstrate bidirectional neural interfacing capabilities, enabling both the delivery of controlled stimulation pulses in physiological buffer and high-resolution neuronal recording in murine brain slices, with machine learning-based event classification. Together, these advances establish PolyGraph as an optimal material platform for next-generation brain-computer interfaces and soft bioelectronic devices. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/673516v1_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@9beea5org.highwire.dtl.DTLVardef@150be08org.highwire.dtl.DTLVardef@1ec24d2org.highwire.dtl.DTLVardef@658209_HPS_FORMAT_FIGEXP M_FIG C_FIG Graphical Abstract & TOC Text PolyGraph, a flexible graphene-polycaprolactone nanocomposite, unites conductivity, biocompatibility, and processability for next-generation neural interfaces. Fabricated into microneedle arrays with ultra-flexible backings, PolyGraph enables bidirectional neuronal recording and stimulation in brain tissue, advancing brain-computer interface (BCI) and soft bioelectronic applications.

bioengineering↗

bioRxiv2024

3D-printed, biomimetic, conductive MXene-microfiber composite scaffolds enhance the axonal growth-promoting characteristics of electrical stimulation.

No effective treatments are currently available for central nervous system neurotrauma although recent advances in electrical stimulation suggest some promise in neural tissue repair. We hypothesized that structured integration of an electroconductive biomaterial into a tissue engineering scaffold could enhance electroactive signalling for neural regeneration. Electroconductive 2D Ti3C2Tx MXene nanosheets were synthesized from MAX-phase powder, demonstrating excellent biocompatibility with neurons, astrocytes and microglia. To achieve spatially-controlled distribution of these MXenes, melt-electrowriting was used to 3D-print highly-organized PCL micro-meshes with varying fibre spacings (low-, medium-and high-density), which were functionalized with MXenes to provide highly-tunable electroconductive properties (0.081{+/-}0.053-18.87{+/-}2.94 S/m). Embedding these electroconductive micro-meshes within a neurotrophic, immunomodulatory hyaluronic acid-based extracellular matrix (ECM) produced a soft, growth-supportive MXene-ECM composite scaffold. Electrical stimulation of neurons seeded on these scaffolds promoted neurite outgrowth, influenced by fibre spacing in the micro-mesh. In a multicellular model of cell behaviour, neurospheres stimulated for 7 days on high-density MXene-ECM scaffolds exhibited significantly increased axonal extension and neuronal differentiation, compared to low-density scaffolds and MXene-free controls. The results demonstrate that spatial-organization of electroconductive materials in a neurotrophic scaffold can enhance repair-critical responses to electrical stimulation and that these biomimetic MXene-ECM scaffolds offer a promising new approach to neurotrauma repair.

bioengineering↗

bioRxiv2019

Multiple Myeloma DREAM Challenge Reveals Epigenetic Regulator PHF19 As Marker of Aggressive Disease

While the past decade has seen meaningful improvements in clinical outcomes for multiple myeloma patients, a subset of patients do not benefit from current therapeutics for unclear reasons. Many gene expression-based models of risk have been developed, but each model uses a different combination of genes and often involve assaying many genes making them difficult to implement. We organized the Multiple Myeloma DREAM Challenge, a crowdsourced effort to develop models of rapid progression in newly diagnosed myeloma patients and to benchmark these against previously published models. This effort lead to more robust predictors and found that incorporating specific demographic and clinical features improved gene expression-based models of high risk. Furthermore, post challenge analysis identified a novel expression-based risk marker and histone modifier, PHF19, which featured prominently in several independent models. Lastly, we show that a simple four feature predictor composed of age, International Staging System stage (ISS), and expression of PHF19 and MMSET performs similarly to more complex models with many more gene expression features included.\n\nKey pointsO_LIMost comprehensive and unbiased assessment of prognostic biomarkers in MM resulting in a robust and parsimonious model.\nC_LIO_LIIdentification of PHF19 as the expression based biomarker most strongly associated with rapid progression in MM patients.\nC_LI

cancer biology↗

bioRxiv2019

Integrative network modeling reveals mechanisms underlying T cell exhaustion

Failure to clear antigens causes CD8+ T cells to become increasingly hypo-functional, a state known as exhaustion. We combined manually extracted information from published literature with gene expression data from diverse model systems to infer a set of molecular regulatory interactions that underpin exhaustion. Topological analysis and simulation modeling of the network suggests CD8+ T cells undergo 2 major transitions in state following stimulation. The time cells spend in the earlier proliferative/pro-memory (PP) state is a fixed and inherent property of the network structure. Transition to the second state is necessary for exhaustion. Combining insights from network topology analysis and simulation modeling, we predict the extent to which each node in our network drives cells towards an exhausted state. We demonstrate the utility of our approach by experimentally testing the prediction that druginduced interference with EZH2 function increases the proportion of proliferative/pro-memory cells in the early days post-activation.

systems biology↗