Biology subjects

Allenby, M. C.

Publications and source records attributed to Allenby, M. C..

15 recordsLinked to original sources

bioRxiv2026

Marrow-mimicry MEW scaffolds recapitulate erythroblastic islands for high-density cRBC biomanufacturing

Biomanufactured cell therapies are delivering a step-change in modern medicine, but their high costs have prevented widespread adoption. Cultured red blood cells (cRBCs) are one type of cell therapy in clinical trials for off-the-shelf blood transfusion but remain limited by the exorbitant costs of manufacturing trillions of RBCs required for a blood transfusion. These costs could be mitigated if culture platforms could grow cells at higher density, like those found in the bone marrow, requiring less media and lower concentrations of expensive growth factors per cell. We engineered melt electrowritten (MEW) polycaprolactone (PCL) scaffolds in geometries which imitate marrow trabeculae structures and were then plasma-treated to enable peripheral blood mononuclear cells (PB MNC) attachment. PB MNC monocytes first adhered to the scaffold and rapidly differentiated into CD68+ macrophage-like cells. These macrophage-loaded scaffolds adhered CD71+ erythroblasts, which then grew from 10 to 25% between days 4 and 8 and produced CD235a+ erythroid cells by day 20, under erythrogenic culture conditions. MEW PCL scaffolds in trabecular-like geometries had greater surface area, adhered more macrophages, and generated more erythroblasts than traditional MEW crosshatch geometries. The MEW scaffolds continuously released less-adherent cells to the supernatant, providing a 74% increase in supernatant cell numbers versus liquid suspension controls with identical cell seeding numbers and media volumes. High-cell-density scaffolds exhibited increased metabolism and endogenous production of self-supportive cytokines, which may offer cost-saving opportunities through future media optimisation. This study reports marrow trabeculae-mimetic MEW PCL designs capable of selectively adhering PB MN cells to develop macrophage-coated scaffolds, which provided physical and paracrine support for cRBC production. This high-cell-density culture platform may be useful for future cell therapy biomanufacturing protocols.

bioengineering↗

bioRxiv2026

Spatially distributed growth factor environments for evaluating hydrogel-based CD34+ cell culture conditions

Suspension culture is the gold standard for ex vivo hematopoietic stem cell (HSC) expansion; however, high media requirement results in expensive cell therapy products. Hydrogel-based HSC culture represents a more realistic in vitro representation of human in vivo HSC microenvironments and may support a more efficient use of media during ex vivo HSC expansion. However, media conditions used for hydrogel-supported cell culture often simply mimic that which are currently used in suspension culture approaches, potentially resulting in an oversupply of cell growth proteins. In this work, we present a microfluidic culture system capable of supporting hydrogel-based cell culture and generating spatial distributions of independent growth factor combinations. Using this device, we image, in real-time, the behaviour of human umbilical cord blood-derived CD34+ cells, within fibrin-based hydrogels, in response to spatial gradients of the human recombinant growth factors stem cell factor, thrombopoietin, angiopoietin-2 and insulin-like growth factor-II. Using live microscopy and image-based single-cell segmentation and quantification, local changes in cell density over time in relation to spatial concentration of factors were identified. This novel microfluidic device has the potential to screen combinations of growth factors required for hydrogel-supported CD34+ cell expansion and inform culture media formulations of future hydrogel-based cell manufacturing processes.

bioengineering↗

bioRxiv2026

Identifying cytokine-release signatures of flow-driven endothelial remodelling in an intracranial aneurysm cell culture model

Intracranial aneurysm (IA) rupture is catastrophic, yet current models of rupture-risk inadequately capture underlying IA remodelling mechanisms. Endothelial-haemodynamic interactions are central to these processes, but in vitro flow platforms often lack vessel-relevant geometry or long-term perfusion. Here, temporal and spatial endothelial responses to haemodynamic stress were investigated across idealised and patient-specific vascular models. Polydimethylsiloxane models were endothelialised with human aortic endothelial cells then perfused at up to 1.6 Pa wall shear stress for five days. IA models were exposed to steady or cardiovascular flow waveforms, with endothelial phenotype assessed by immunofluorescence and cytokine profiling. Flow initiation induced a transient inflammatory response, with elevated MCP-1 and TNF- at day two, followed by a resolution of cytokine levels by day five, including a [~]7.5-fold reduction in MCP-1, despite increased haemodynamic loading. Endothelial cells retained a cobblestone-like morphology with eNOS undetected, resembling a partially activated phenotype. Compared with steady flow, cardiovascular flow reduced TGF-{beta}1 and IL-8 secretion and decreased FGF-b consumption ([~]2.5 fold), suggesting enhanced phenotypic stability. This study presents the first in vitro IA model incorporating a cardiovascular flow waveform and identifies cytokine signatures with potential utility as biomarkers of IA remodelling, highlighting the importance of long-term perfusion for modelling chronic vascular disease. Table of Contents FigureAn in vitro model of an intracranial aneurysm was developed to investigate how fluid flow dynamics impact endothelial remodelling and inflammation. Pulsatile cardiac flow promoted stabilisation of inflammatory signalling, which was sustained under a steady flow regime. Cytokine signatures emerged with potential utility as biomarkers of IA remodelling, highlighting the importance of long-term perfusion for modelling chronic vascular disease. The schematic of the cytokine release dynamics used in the graphical abstract below was generated with the assistance of AI-based tools including ChatGPT (v5.5) and M365 Copilot to align with key results from this manuscript. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=182 SRC="FIGDIR/small/733289v1_ufig1.gif" ALT="Figure 1000"> View larger version (80K): org.highwire.dtl.DTLVardef@709204org.highwire.dtl.DTLVardef@825f81org.highwire.dtl.DTLVardef@14c345eorg.highwire.dtl.DTLVardef@222a8_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2026

Thermodynamic phase-field modelling predicts non-linear evolution of tumour spheroid dynamics

Patient-derived tumour spheroids provide experimentally tractable models of tumour growth and treatment response, but standard radius-based measurements do not directly identify the tissue-scale mechanisms that shape internal structure. This study develops and calibrates a thermodynamic continuum model of untreated spheroid internal structural growth, in which viable and necrotic cell populations, nutrient transport, mechanical relaxation, and cell-fate transitions are represented as coupled spatial fields. Because the model does not prescribe internal concentric spheroid compartments like traditional spheroid models, the experimentally reported intermediate (inhibited) radius was treated as an exploratory model-to-data mapping and optimised over different candidate field-derived radii. The calibrated model reproduced the experimental trajectories with aggregate uncertainty-weighted root-mean-square error (WRMSE) values ranging from 0.49 to 1.24 on the metric defined in the manuscript, and improved average fit quality by approximately 40% relative to an existing Greenspan-type compartment model. The model recovered the growth-inhibited and necrotic structure observed in spheroids as an emergent consequence of spatial cell-state dynamics rather than prescribing concentric compartments. Biological and nutrient-associated model parameters were locally constrained to the experimental data, although compensatory relationships were observed among nutrient-response and death parameters. The framework was further extended by introducing a drug transport field as a proof-of-concept demonstration of spatial treatment-response modelling. These results show that a continuum cell-growth model can recover classical spheroid structure while preserving flexibility for exploratory field-based analysis of drug response.

bioengineering↗

bioRxiv2025

Additive manufacturing of patient-specific intracranial aneurysm cell culture models

Intracranial aneurysms (IAs) are present in 2-6% of the global population. While rare, rupture results in mortality rates of 30-50% and lifelong disabilities in survivors. While treatment of unruptured IAs carries its own risk of mortality, there are no rigid guidelines indicating which IA presentation is at greater risk of rupture. We develop and evaluate the suitability of various additive manufacturing processes to fabricate patient-specific IA culture models for understanding IA pathophysiology and thereby support future development of a rupture risk prediction tool. Material compatibility of several 3D printed resins, polydimethylsiloxane (PDMS) and collagen gel with immortalised human brain endothelial cells (HBECs) were investigated. Patient angiograms were segmented to produce in vitro models via two fabrication approaches: stereolithography (SLA) 3D printing versus chocolate injection moulding of a sacrificial core embedded in PDMS. These 3D arterial models were then cellularised with HBECs, and geometric accuracy and distension properties evaluated. PDMS, collagen gel and the elastic50A resin materials supported cellularisation on material surfaces with high cell viability and proliferation. Both the 3D printed resin and injection moulding techniques successfully fabricated patient-specific basilar artery IA models with a Dice-Sorensen coefficient of over 90%. However, only PDMS models offered complete cell coverage in 3D geometries. This exceeds current benchmarks on IA fabrication accuracy. Through controlling IA model wall thickness, we demonstrate the ability to create localised distension under pressure in the context of thin- and thick-walled aneurysms. In vitro IA models present a promising platform for investigating IA pathophysiology and rupture risk. The novel chocolate sacrificial core technique offers a biocompatible, support-free fabrication method suitable for 3D cultures. Given the independent effects of fluid dynamics and mechanical strain on cell behaviour, it is essential to characterise distension under pressure and ensure accurate fabrication for reliable analysis into cell behaviour.

bioengineering↗

bioRxiv2025

The Batch-Resourcing Angiogenesis Tool (BRAT) to enable high-content microscopy screening of microvascular networks.

Vessel forming assays are a valuable in vitro technology to evaluate the vasculogenic and angiogenic potential of different cell types, matrix proteins, and soluble factors. Recent advances in high-content microscopy allow for vascular morphogenesis assays to be captured in real-time and in high-throughput screening purposes. Unfortunately, existing microvascular network quantification algorithms are either inaccurate, not user-friendly, or manually analyse one image at a time, unfavourable to high-content screening applications. This manuscript introduces BRAT, the Batch-Resourcing Angiogenesis Tool, a computer algorithm with an open-source graphic user interface to efficiently segment, skeletonize, and analyse large batches of vascular network images with high accuracy. Benchmarked across diverse clinical and cultured microvascular network images, BRAT is the most sensitive vascular network image analysis tool (94.5%) and exhibits leading accuracy (93.3%). BRATs multi-threaded processing automatically analysed 886 microscopy images at a speed of 0.17 seconds/image (2:29 minutes) on a performance computer or 2.31 seconds/image (34:04) on a typical laptop. This is 10-to-100 fold more time-efficient than existing tools, which require 12 to 16 seconds of direct user input per image. BRAT is broadly useful to analyse vessel networks of different endothelial cell types cultured on 2D substrates and within 3D biomaterials. BRAT represents a powerful approach for the accurate and high-content screening of vessel forming assays for disease models, regenerative medicines, and therapeutic testing.

bioengineering↗

bioRxiv2025

Fabricating microfluidic co-cultures of immortalised cell lines uncovers robust design principles for the simultaneous formation of patterned, vascularised, and stem cell-derived adipose tissue.

In vitro culture processes supporting the simultaneous formation of vessel networks alongside differentiation towards mature parenchymal tissue have numerous clinical and agricultural applications but remain unrealised due to contrasting culture requirements. Of specific interest is lab-grown vascularised adipose tissue to study metabolic syndrome, diabetes, obesity, cardiovascular diseases, and to advance cultivated meat technologies. We report a microfluidic 3D hydrogel culture device capable of supporting live-imaging of fluorescent reporter cell lines and generating counter-current gradients of vasculogenic and adipogenic growth factors. for the first time, we report experimental conditions capable of reproducibly forming diverse microvascular networks from telomerase immortalised endothelial and mesenchymal stem cells in both 2D and 3D hydrogel-embedded cultures. Using our novel microfluidic culture design, we demonstrate the generation of growth factor environments which support the 3D co-formation of integrated robust microvascular networks and lipid-producing adipocytes after 31 days gradient culture. We demonstrate microvascular networks substantially support parenchymal stromal cell differentiation to mature adipose tissue (67.4% lipid coverage), unachieved in avascular cultures (1.86% lipid coverage). We attempt to validate our co-culture model by applying inhibitors of vessel-mediated lipogenesis (spermidine and VO-OHpic), which are demonstrated to be ineffective in our novel human preclinical model. HighlightsO_LIAn optimised co-culture protocol for vasculogenesis of immortalised cell lines. C_LIO_LIImmortalised co-cultures form reproducible microvessel networks up to 31 days. C_LIO_LIGradient co-culture enables simultaneous MSC adipogenesis and EC vasculogenesis. C_LIO_LIMSC differentiation to dense, lipid-laden adipose tissue relies on EC co-culture. C_LIO_LIHuman vascularised adipose tissue formation is unaffected by a murine regulator. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC="FIGDIR/small/634386v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@4b3567org.highwire.dtl.DTLVardef@19f0278org.highwire.dtl.DTLVardef@5b3d1eorg.highwire.dtl.DTLVardef@9a5c9_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2024

Haemodynamic impact of implant materials and anastomotic angle in peripheral vascular grafts

End-to-side anastomoses are commonly utilised in peripheral arterial bypass surgery and are plagued by high rates of re-stenosis as a result of non-physiological blood flow impacting arterial and graft structures. Computational simulations can examine how patient-specific surgical decisions in bypass graft placement and material selection affect blood flow and future risk of graft restenosis. Despite graft geometry and compliance being key predictors of restenosis, current simulations do not consider the interaction of flowing blood with compliant vessel, graft, and suture structures. Utilising fluid-structure interaction simulations, this study examines the impact of surgical technique, such as anastomosis angle, graft material, and suture material, on blood flow and fluid-structure forces in patient-specific asymptomatic arterial tree versus side-to-end peripheral grafts for symptomatic atherosclerotic disease. To render these complex simulations numerically feasible, our pipeline uses regional suture mechanics and a pre-stress pipeline previously validated in small-scale idealised models. Our simulations found that higher anastomosis angles generate larger regions of slow and recirculating blood, characterised by non-physiologically low shear stress and high oscillatory shear index. The use of compliant graft materials reduces regions of non-physiologically high shear stress only when used in combination with compliant suture materials. Altogether, our fluid-structure interaction simulation provides patient-specific platforms for vascular surgery decisions concerning graft geometry and material. HighlightsO_LISimulating bypass graft haemodynamics with realistic fluid-structure interactions. C_LIO_LIBypass grafts generate large regions of slow blood flow and blood recirculation. C_LIO_LIGreater graft anastomosis angles correlate with larger blood recirculation regions. C_LIO_LINonphysiologically stiff graft and suture materials increase vessel shear stress. C_LI

bioengineering↗

bioRxiv2024

Simulating big mechanically-active culture systems (BigMACS) using paired biomechanics-histology FEA modelling to derive mechanobiology design relationships.

Big mechanically-active culture systems (BigMACS) are promising to stimulate, control, and pattern cell and tissue behaviours with less soluble factor requirements, however, it remains challenging to predict if and how distributed mechanical forces impact single-cell behaviours to pattern tissue. In this study, we introduce a centimetre, tissue-scale, finite element analysis (FEA) framework able to correlate sub-cellular quantitative histology with centimetre-scale biomechanics. Our framework is relevant to diverse bigMACS; media perfusion, tensile-stress, magnetic, and pneumatic tissue culture platforms. We apply our framework to understand how the design and operation of a multi-axial soft robotic bioreactor can spatially control mesenchymal stem cell (MSC) proliferation, orientation, differentiation to smooth muscle, and extracellular vascular matrix deposition. We find MSC proliferation and matrix deposition correlate positively with mechanical stimulation but cannot be locally patterned by soft robot mechanical stimulation within a centimetre scale tissue. In contrast, local stress distribution was able to locally pattern MSC orientation and differentiation to smooth muscle phenotypes, where MSCs aligned perpendicular to principal stress direction and expressed increased -SMA with increasing 3D Von Mises Stresses from 0 to 15 kPa. Altogether, our new biomechanical-histological simulation framework is a promising technique to derive the future mechanical design equations to control cell behaviours and engineer patterned tissue generation.

bioengineering↗

bioRxiv2023

Advancing scaffold biomimicry: engineering mechanics in microfiber scaffolds with independently controlled architecture using melt electrowriting

Melt electrowriting (MEW) is an additive manufacturing technique characterized by its ability to fabricate micronscale fibers from molten polymers into highly controlled 3D microfiber scaffolds. This emerging technique is gaining traction in tissue engineering and biofabrication research, however limitations in the ability to develop advanced coding to program MEW printers to fabricate scaffolds with complex fiber architectures has inhibited the development of structures with tunable and biomimetic mechanical properties. This study reports a series of non-straight scaffold architectures with combinations of independently controlled X & Y fiber spacing, corrections for MEW jet lag, and characterizations of their influences on scaffold mechanics. Polycaprolactone scaffolds with an elastic modulus ranging from 0.3 to 7.3 MPa were fabricated utilizing scaffolds manufactured from 5 layers of 55 m fibers. The inclusion of scaffold design corrections in the gcode to compensate for decreasing deposition accuracy with increasing layer height enabled us to correct for discontinuous stress-strain mechanics and improved scaffold fabrication reproducibility. This study provides a comparison between a series of highly reproducible MEW scaffold architectures with non-straight fibers compared to the common crosshatch design to inform the development of more biomimetic scaffolds applicable to a variety of clinical applications. It further illustrates the significant effect toolpath correction has on reducing poor stress-strain mechanics, therefore improving the control, reproducibility, and biomimetic capacity of the MEW technique.

bioengineering↗

bioRxiv2023

Fluid-Structure Interactions of Peripheral Arteries Using a Coupled in silico and in vitro Approach

Vascular compliance is considered both a cause and a consequence of cardiovascular disease and a significant factor in the mid- and long-term patency of vascular grafts. However, the biomechanical effects of localised changes in compliance, such as during plaque development or after bypass grafting and stenting, cannot be satisfactorily studied with the available medical imaging technologies or surgical simulation materials. To address this unmet need, we developed a coupled silico-vitro platform which allows for the validation of numerical fluid-structure interaction (FSI) results as a numerical model and physical prototype. This numerical one-way and two-way FSI study is based on a three-dimensional computer model of an idealised femoral artery which is validated against patient measurements derived from the literature. The numerical results are then compared with experimental values collected from compliant arterial phantoms. Phantoms within a compliance range of 1.4 - 68.0%/100mmHg were fabricated via additive manufacturing and silicone casting, then mechanically characterised via ring tensile testing and optical analysis under direct pressurisation with differences in measured compliance ranging between 10 - 20% for the two methods. One-way FSI coupling underestimated arterial wall compliance by up to 14.71% compared to two-way FSI modelling. Overall, Smooth-On Solaris matched the compliance range of the numerical and in vivo patient models most closely out of the tested silicone materials. Our approach is promising for vascular applications where mechanical compliance is especially important, such as the study of diseases which commonly affect arterial wall stiffness, such as atherosclerosis, and the model-based design, surgical training, and optimisation of vascular prostheses.

bioengineering↗

bioRxiv2021

Bio-hybrid Soft Robotic Bioreactors for Mimicking Multi-Axial Femoropopliteal Artery Mechanobiology

The emerging field of soft robotics aims to emulate dynamic physiological locomotion. Soft robotics mimicry of naturally complex biomechanics makes them ideal platforms for exerting mechanical stimuli for patient-specific tissue maturation and disease modeling applications. Such platforms are essential for emulating highly flexible tissues such as the kneecaps femoropopliteal artery (FPA), one of the most flexible arteries in the body, which flexes and bends during walking, standing, and crouching movements. The FPA is a frequent site of disease, where 80% of all peripheral artery diseases manifest, affecting over 200 million people worldwide. The complex biomechanical and hemodynamic forces within the FPA have been implicated in the frequent occurrence of PAD and lead to debilitating morbidities, such as limb-threatening ischemia. To better mimic these complex biomechanics, we developed an in-vitro bio-hybrid soft robot (BSR). First, Platsil OO-20 was identified as an ideal hyperelastomer for both cell culture and BSR fabrication using 3D printed molds. Then, employing a simulation-based design workflow, we integrated pneumatic network (PneuNet) actuators cast with Platsil OO-20, which extend in angular, longitudinal, and radial dimensions. Pressurizing the BSR PneuNets enabled a range of mechanical stimuli to be dynamically applied during tissue culture to mimic normal and diseased FPA flexions during daily walking and sitting poses, the most extreme being radial distensions of 20% and angular flexions of 140{degrees}. Finally, these designed, manufactured, and programmed vascular BSRs were seeded with mesenchymal stem cells and conditioned for 24 hours to highlight the effect of dynamic conditioning on cultured cell alignment, as well as type IV collagen production and the upregulation of smooth muscle phenotypes. Soft robotic bioreactor platforms that accurately mimic patient-, disease-, and lifestyle-specific mechanobiology will develop fundamental disease understanding, preoperative laboratory simulations for existing therapeutics, and biomanufacturing platforms for tissue-engineered implants.

bioengineering↗

bioRxiv2021

Model-based data analysis of tissue growth in thin 3D printed scaffolds

Tissue growth in three-dimensional (3D) printed scaffolds enables exploration and control of cell behaviour in biologically realistic geometries. Cell proliferation and migration in these experiments have yet to be explicitly characterised, limiting the ability of experimentalists to determine the effects of various experimental conditions, such as scaffold geometry, on cell behaviour. We consider tissue growth by osteoblastic cells in melt electro-written scaffolds that comprise thin square pores with sizes that we deliberately vary. We collect highly detailed temporal measurements of the average cell density, tissue coverage, and tissue geometry. To quantify tissue growth in terms of the underlying cell proliferation and migration processes, we introduce and calibrate a mechanistic mathematical model based on the Porous-Fisher reaction-diffusion equation. Parameter estimates and uncertainty quantification through profile likelihood analysis reveal consistency in the rate of cell proliferation and steady-state cell density between pore sizes. This analysis also serves as an important model verification tool: while the use of reaction-diffusion models in biology is widespread, the appropriateness of these models to describe tissue growth in 3D scaffolds has yet to be explored. We find that the Porous-Fisher model is able to capture features relating to the cell density and tissue coverage, but is not able to capture geometric features relating to the circularity of the tissue interface. Our analysis identifies two distinct stages of tissue growth, suggests several areas for model refinement, and provides guidance for future experimental work that explores tissue growth in 3D printed scaffolds. Author SummaryAdvances in 3D printing technology have led to cell culture experiments that realistically capture natural biological environments. Despite the necessity of quantifying cell behaviour with parameters that can be compared between experiments, many existing mathematical models of tissue growth in these experiments neglect information relating to population size. We consider tissue growth by cells on 3D printed scaffolds that comprise square pores of various sizes in this work. We apply a relatively simple mathematical model based on the Porous-Fisher reaction-diffusion equation to interpret highly detailed measurements relating to both the cell density and the quantity of tissue deposited. We analyse the efficacy of such a model in capturing cell behaviour seen in the experiments and quantify cell behaviour in terms of parameters that carry a biologically meaningful interpretation. Our analysis identifies important areas for model refinement and provides guidance for future data-collection and experimentation that explores tissue growth in 3D printed scaffolds.

cell biology↗

bioRxiv2020

Detection of clustered anomalies in single-voxel morphometry as a rapid automated method for identifying intracranial aneurysms.

Unruptured intracranial aneurysms (UIAs) are prevalent neurovascular anomalies which, in rare circumstances, rupture to create a catastrophic subarachnoid haemorrhage. Although surgical management can reduce rupture risk, the majority of IAs exist undiscovered until rupture. Current computer-aided UIA diagnoses sensitively detect and measure UIAs within cranial angiograms, but remain limited to low specificities whose output requires considerable neuroradiologist interpretation not amenable to broad screening efforts. To address these limitations, we propose an analysis which interprets single-voxel morphometry of segmented neurovasculature to identify UIAs. Once neurovascular anatomy of a specified resolution is segmented, interrelationships between voxel-specific morphometries are estimated and spatially-clustered outliers are identified as UIA candidates. Our automated solution detects UIAs within magnetic resonance angiograms (MRA) at unmatched 86% specificity and 81% sensitivity using 3 minutes on a conventional laptop. Our approach does not rely on interpatient comparisons or training datasets which could be difficult to amass and process for rare incidentally discovered UIAs within large MRA files, and in doing so, is versatile to user-defined segmentation quality, to detection sensitivity, and across a range of imaging resolutions and modalities. We propose this method as a unique tool to aid UIA screening, characterisation of abnormal vasculature in at-risk patients, morphometry-based rupture risk prediction, and identification of other vascular abnormalities. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC="FIGDIR/small/216812v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@166f3aborg.highwire.dtl.DTLVardef@76ea1org.highwire.dtl.DTLVardef@1f03619org.highwire.dtl.DTLVardef@16fd797_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract C_FIG Highlights O_LIRapid and automated detection of unruptured intracranial aneurysms (UIAs) in MRAs C_LIO_LIHighly specific, sensitive UIA detection to reduce radiologist input for screening C_LIO_LIDetection is versatile to image resolution, modality and has tuneable mm sensitivity C_LI

bioinformatics↗

bioRxiv2020

Cell proliferation and migration explain pore bridging dynamics in 3D printed scaffolds of different pore size

Tissue growth in bioscaffolds is influenced significantly by pore geometry, but how this geometric dependence emerges from dynamic cellular processes such as cell proliferation and cell migration remains poorly understood. Here we investigate the influence of pore size on the time required to bridge pores in thin 3D-printed scaffolds. Experimentally, new tissue infills the pores continually from their perimeter under strong curvature control, which leads the tissue front to round off with time. Despite the varied shapes assumed by the tissue during this evolution, we find that time to bridge a pore simply increases linearly with the overall pore size. To disentangle the biological influence of cell behaviour and the mechanistic influence of geometry in this experimental observation, we propose a simple reaction-diffusion model of tissue growth based on Porous-Fisher invasion of cells into the pores. First, this model provides a good qualitative representation of the evolution of the tissue; new tissue in the model grows at an effective rate that depends on the local curvature of the tissue substrate. Second, the model suggests that a linear dependence of bridging time with pore size arises due to geometric reasons alone, not to differences in cell behaviours across pores of different sizes. Our analysis suggests that tissue growth dynamics in these experimental constructs is dominated by mechanistic crowding effects that influence collective cell proliferation and migration processes, and that can be predicted by simple reaction-diffusion models of cells that have robust, consistent behaviours.

bioengineering↗