Jack Maughan

Disruption of the wound healing cascade can result in pathological outcomes, including fibrosis due to myofibroblast-mediated contraction and collagen deposition. Despite the clinical significance, effective treatments for fibrosis remain limited as current therapies often show inconsistent efficacy, adverse effects, and patient discomfort. Combinatorial therapeutic strategies integrating biomaterial scaffolds with gene delivery have shown promise in regenerative healing. MicroRNAs (miRNAs) are key regulators of fibrotic signalling in cells, including fibroblasts and myofibroblasts. Specifically, miRNA-29b is notable for downregulating pro-fibrotic genes, including collagen type I, reducing ECM accumulation, and limiting fibroblast/myofibroblast overactivation. In this context, the present work develops a collagen-GAG (CG) scaffold platform for delivery of miRNA-29b complexed GET nanoparticles to inhibit fibrosis. Initially, bioinformatic analysis of miRNA-29b validated its involvement in ECM-associated pathways and processes, followed by successful nanoparticle internationalisation in primary dermal fibroblasts. The anti-fibrotic efficacy of the optimised miRNA-29b nanoparticles was subsequently demonstrated by significant reductions in collagen deposition and -SMA expression, both key indicators of myofibroblast differentiation and fibrosis. The optimised miRNA-29b formulation was then incorporated into 3D porous collagen-GAG (CG) scaffolds, which modulated fibrotic gene expression while preserving scaffold structure conducive to fibroblast/myofibroblast infiltration and proliferation. Finally, functional outcomes of seeded TGF--stimulated fibroblasts, including reduced matrix contraction, -SMA expression, and ECM deposition, were comparable to those observed in non-fibrotic conditions, thereby confirming the therapeutic potential of scaffold-mediated miRNA-29b delivery. Together, these findings demonstrate that scaffold-mediated miRNA-29b delivery represents a promising anti-fibrotic strategy for wound healing by mitigating myofibroblast activation, limiting matrix contraction, and preventing pathological ECM accumulation.

MXenes (Ti ₃ C ₂ T _x ) are two‐dimensional (2D) layered nanomaterials typically processed as aligned flakes. However, their morphology can also be engineered into crumpled architectures with distinct physicochemical properties that remain largely unexplored. Here, Aerosol Jet Printing (AJP) is established as a scalable manufacturing strategy to tailor MXene flake morphology through precise control of the printing conditions. By repurposing the printer's built‐in alignment camera, a rapid monitoring method was developed to distinguish aligned and crumpled morphologies during fabrication. Systematic investigation of the printing parameters identified mass flow, nozzle size, and ink concentration as the key variables governing flake morphology, demonstrating its general applicability on other 2D materials, such as graphene and MoS ₂ . Aligned MXene films achieved electrical conductivities of up to 2672 ± 125 S cm ^{− 1} , whereas crumpled films exhibited increased roughness and hydrophilicity. The engineered morphologies were further validated across multiple applications, including neural interfaces, antimicrobial coatings, and strain sensors. Both morphologies supported excellent biocompatibility with primary neurons and human induced pluripotent stem cell‐derived neural cells, while crumpled MXenes enhanced antibacterial activity against Staphylococcus aureus and improved strain‐sensing performance. These findings highlight the importance of controlling the morphology of 2D materials during 3D printing, providing a scalable route toward multifunctional biomedical devices.

Disruption of the wound healing cascade can result in pathological outcomes, including fibrosis due to myofibroblast-mediated contraction and collagen deposition. Despite the clinical significance, effective treatments for fibrosis remain limited as current therapies often show inconsistent efficacy, adverse effects, and patient discomfort. Combinatorial therapeutic strategies integrating biomaterial scaffolds with gene delivery have shown promise in regenerative healing. MicroRNAs (miRNAs) are key regulators of fibrotic signalling in cells, including fibroblasts and myofibroblasts. Specifically, miRNA-29b is notable for downregulating pro-fibrotic genes, including collagen type I, reducing ECM accumulation, and limiting fibroblast/myofibroblast overactivation. In this context, the present work develops a collagen-GAG (CG) scaffold platform for delivery of miRNA-29b complexed GET nanoparticles to inhibit fibrosis. Initially, bioinformatic analysis of miRNA-29b validated its involvement in ECM-associated pathways and processes, followed by successful nanoparticle internationalisation in primary dermal fibroblasts. The anti-fibrotic efficacy of the optimised miRNA-29b nanoparticles was subsequently demonstrated by significant reductions in collagen deposition and a-SMA expression, both key indicators of myofibroblast differentiation and fibrosis. The optimised miRNA-29b formulation was then incorporated into 3D porous collagen-GAG (CG) scaffolds, which modulated fibrotic gene expression while preserving scaffold structure conducive to fibroblast/myofibroblast infiltration and proliferation. Finally, functional outcomes of seeded TGF-b-stimulated fibroblasts, including reduced matrix contraction, a-SMA expression, and ECM deposition, were comparable to those observed in non-fibrotic conditions, thereby confirming the therapeutic potential of scaffold-mediated miRNA-29b delivery. Together, these findings demonstrate that scaffold-mediated miRNA-29b delivery represents a promising anti-fibrotic strategy for wound healing by mitigating myofibroblast activation, limiting matrix contraction, and preventing pathological ECM accumulation.

Disruption of the wound healing cascade can result in pathological outcomes, including fibrosis due to myofibroblast-mediated contraction and collagen deposition. Despite the clinical significance, effective treatments for fibrosis remain limited as current therapies often show inconsistent efficacy, adverse effects, and patient discomfort. Combinatorial therapeutic strategies integrating biomaterial scaffolds with gene delivery have shown promise in regenerative healing. MicroRNAs (miRNAs) are key regulators of fibrotic signalling in cells, including fibroblasts and myofibroblasts. Specifically, miRNA-29b is notable for downregulating pro-fibrotic genes, including collagen type I, reducing ECM accumulation, and limiting fibroblast/myofibroblast overactivation. In this context, the present work develops a collagen-GAG (CG) scaffold platform for delivery of miRNA-29b complexed GET nanoparticles to inhibit fibrosis. Initially, bioinformatic analysis of miRNA-29b validated its involvement in ECM-associated pathways and processes, followed by successful nanoparticle internationalisation in primary dermal fibroblasts. The anti-fibrotic efficacy of the optimised miRNA-29b nanoparticles was subsequently demonstrated by significant reductions in collagen deposition and α-SMA expression, both key indicators of myofibroblast differentiation and fibrosis. The optimised miRNA-29b formulation was then incorporated into 3D porous collagen-GAG (CG) scaffolds, which modulated fibrotic gene expression while preserving scaffold structure conducive to fibroblast/myofibroblast infiltration and proliferation. Finally, functional outcomes of seeded TGF-β-stimulated fibroblasts, including reduced matrix contraction, α-SMA expression, and ECM deposition, were comparable to those observed in non-fibrotic conditions, thereby confirming the therapeutic potential of scaffold-mediated miRNA-29b delivery. Together, these findings demonstrate that scaffold-mediated miRNA-29b delivery represents a promising anti-fibrotic strategy for wound healing by mitigating myofibroblast activation, limiting matrix contraction, and preventing pathological ECM accumulation.

Chronic wounds represent a significant clinical challenge due to persistent inflammation and impaired nerve regeneration that delay healing. Conventional treatments often yield inconsistent and limited success. Combinatorial strategies that integrate biomaterial scaffolds with gene delivery offer a promising approach to promote tissue repair. MicroRNAs (miRNAs), particularly miRNA-155, are key regulators of wound healing. miRNA-155 is highly expressed in inflammatory conditions and modulates 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 incorporated into collagen-glycosaminoglycan (CG) scaffolds. Scaffold-mediated miRNA-155 inhibition in both non-polarised (M0) and pro-inflammatory (M1) macrophages promoted anti-inflammatory (M2) polarisation, confirmed by molecular and protein analysis. The regenerative potential of this macrophage polarisation was validated through inflammatory and angiogenic functional assays with endothelial cells. In parallel, scaffold-mediated miRNA-155 inhibition in dorsal root ganglia (DRG) enhanced axonal regrowth, essential for the synergistic repair of chronic wounds across the skin-nerve axis. In vivo implantation in a chick model demonstrated successful scaffold integration without disrupting vascular development. Collectively, these findings establish the miRNA-155 inhibitor-activated scaffold as a multi-faceted regenerative platform with anti-inflammatory, angiogenic, and neurogenic outcomes for chronic wound healing applications.

This study showcases the successful development of a PTEN-siRNA activated scaffold for SCI repair applications. Initially, siRNA was combined with the novel non-viral glycosaminoglycan-binding enhanced transduction (GET) peptide vector (image of GET vector from [22]). The formulated GET-siRNA nanoparticles effectively transfected primary neurons, a cell type generally considered challenging to transfect. Subsequently, siRNA-nanoparticles were incorporated into a hyaluronic acid scaffold enriched with neurotrophic extracellular matrix proteins (collagen IV and fibronectin) developed by our laboratory for spinal cord repair applications. Functionalisation of these scaffolds with PTEN-siRNA nanoparticles significantly enhanced their capacity to promote neurite outgrowth. Image 1

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. Optimized liquid‐phase exfoliation produces conductive, biocompatible PVP‐stabilized 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 Ω cm ² @ 1 kHz) and high charge injection capacity (11.7 mC/cm ² 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.

Significant challenges in spinal cord injury include the loss of neural tissue, disruption of local vasculature, and intrinsic suppression of actin mobilisation in neurons, together preventing axonal regrowth. Here, we develop an implantable biomimetic microRNA (miR) inhibitor-activated scaffold that combines optimised matrix cues with transcriptomically defined RNA-based modulation of intrinsic neuronal pathways as a platform to support neuronal cell delivery and promote neurovascular repair. First, hyaluronic acid macroporous scaffolds functionalized with collagen IV and fibronectin supported iPSC-derived neuronal spheroid formation and neurite extension. To identify a neurotrophic target, we performed analysis of public miRNA-mRNA interaction datasets, revealing that miR-133a regulates pathways involved in neuronal actin cytoskeletal organisation. MiR-133a inhibitors were complexed with the cell-penetrating peptide RALA to form nanoparticles, demonstrated >95% scaffold loading efficiency, sustained localised release over 28 days and enhanced neurite outgrowth from motor neurons and iPSC neurons. Bulk RNA sequencing and transcriptomic analysis of iPSC neurons within the scaffolds demonstrated coordinated upregulation of actin remodelling, cell-matrix adhesion and metabolic pathways, indicative of a cytoskeletally adaptable neuron. When employed in an ex vivo dorsal root ganglia model, scaffold-mediated miR-133a inhibition promoted neurite extension and integration of delivered iPSC neurons with injured neural tissue. Finally, miR-133a-inhibitor-activated scaffolds upregulated neurovascular genes, increased endothelial cell migration and enhanced blood vessel formation in vivo in a chick embryo assay. These findings identify miR-133a as a neurotrophic target, elucidate the underlying mechanisms of action through transcriptomic analysis and demonstrate that biomimetic scaffold-mediated inhibition of miR-133a can enhance neuronal delivery for multifaceted spinal cord repair applications.

Two‐dimensional boron offers unique advantages in bone tissue engineering, unlocking capabilities that conventional additives struggle to achieve. Herein, the 2D morphology and intrinsic bioactivity of boron nanoplatelets are leveraged, to be incorporated into collagen‐based scaffolds and simultaneously achieve osteogenic, mechanically reinforcing, and antimicrobial effects, with a shift toward neurogenic, angiogenic, and anti‐inflammatory signaling. Boron nanoplatelets, synthesized from nonlayered precursors using liquid‐phase exfoliation, are combined with collagen to form boron‐collagen scaffolds (BColl). Boron significantly reinforces the collagen matrix, beneficial for mechanoresponsive bone cells. Osteoblasts and mesenchymal stem cells exhibit healthy morphology and proliferation on BColl films and scaffolds, with extended culture leading to increased alkaline phosphatase release and significantly increased calcium deposition, indicating enhanced osteogenesis. E. coli viability decreases significantly on BColl films, demonstrating their potential to limit postimplantation infections. Finally, angiogenic, neurogenic, and anti‐inflammatory signaling, with dose‐dependent upregulation of vascular endothelial growth factor‐A, nerve growth factor‐beta, and interleukin‐10, and downregulation of interleukin‐6 are observed, highlighting boron's potential to drive pro‐reparative processes. Taken together, these data showcase boron's potential for next‐generation bone biomaterials, by offering multifunctional benefits to clinically relevant aspects of bone regeneration such as mineralization, angiogenesis, and innervation, while improving the mechanical and antimicrobial properties of natural polymer scaffolds.

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