Intracranial-pressure transients impose mechanical strain on perivascular astrocytes, but it is unclear whether brief mechanical events elicit metabolic responses. Here, we applied 1.5-s pressure-driven mechanical stimuli (5-1,000 hPa) to cultured primary rat cortical astrocytes using a patch-micropipette microinjector and monitored cytosolic lactate ([lactate]i) with a Förster resonance energy transfer Laconic nanosensor. Single pressure pulses (5-1,000 hPa) evoked a pressure-dependent increase in [lactate]i that persisted for minutes after stimulation, reaching a steady-state increase of 0.3-4.1% relative to baseline over 200-300 s. Sequential pulses delivered to the same cell produced transient spikes followed by stepwise increases in the post-stimulus plateau, yielding an estimated activation threshold of ~4-5 hPa. Transient receptor-potential vanilloid-4 (TRPV4) immunoreactivity was detected in cultured astrocytes, and pharmacologic inhibition of TRPV4 with HC-067047 attenuated mechanically evoked lactate accumulation during mechanical stimulation by solution bolus addition. These findings demonstrate that astrocytes convert brief mechanical stimuli into prolonged cytosolic lactate increases, supporting a contribution of TRPV4-associated mechanosensitive signaling to astrocytic mechano-metabolic integration.
Atrophic acne scars result from impaired dermal repair following inflammation of the pilosebaceous unit, leading to collagen degradation, dermal atrophy, and tethering by fibrotic strands. Conventional subcision mechanically releases these adhesions but provides limited biologic stimulation for dermal remodeling. Carbon dioxide (CO₂) gas subcision has emerged as a hybrid mechanical-biologic modality that integrates fibrotic release with CO₂ -induced vasodilation, microcirculatory enhancement, and fibroblast activation. To describe the clinical use and short-term outcomes of CO₂ gas subcision for atrophic acne scars and explore its potential as a minimally invasive hybrid treatment. CO₂ device (Trifill Pro, South Korea) and PDLLA (Juvelook, VAIM Inc., South Korea) was used in the study. A temperature-regulated medical-grade CO₂ system delivered controlled intradermal gas through a 30-gauge needle. Short CO₂ bursts were administered into the deep dermal or upper subcutaneous plane to detach fibrotic bands while inducing hypercapnia-associated biologic responses. Five patients with atrophic acne scars underwent a single session. Follow-up at weeks 2 and 4 included standardized photography, clinical assessment of scar depth and contour, and patient-reported satisfaction using a 0-10 Visual Analogue Scale (VAS). Five patients completed follow-up at 4 weeks. All patients demonstrated qualitative improvement in scar depth and contour on clinical assessment. Mean patient satisfaction score (VAS) was high (range 7-9). No serious adverse events were observed. Mild transient erythema and edema resolved spontaneously within hours. Due to the small sample size and short follow-up, results are descriptive rather than statistically powered. CO₂ gas subcision appears to be a feasible and well-tolerated minimally invasive technique combining mechanical fibrotic release with biologic stimulation. This pilot case series suggests short-term improvement in atrophic acne scars; however, larger controlled studies with longer follow-up are required to confirm efficacy and durability. VBlinded manuscript without author contact information.
To compare total hospital costs associated with remifentanil versus fentanyl for analgosedation in mechanically ventilated intensive care unit (ICU) patients, given increasing interest in remifentanil as a feasible alternative, but limited economic evidence. Cost analysis of a single-centre, prospective, randomised controlled trial (remi-fent1 RCT). Nepean Hospital ICU, New South Wales, Australia. Adult patients admitted between June 2020 and August 2021 requiring invasive mechanical ventilation (IMV) who were randomised to receive remifentanil or fentanyl as part of their analgosedation regimen. The primary outcome was total hospital bed-day costs (Australian Dollars), estimated from a healthcare payer perspective using the Australian Independent Hospital Pricing Authority National Pricing Model for the financial year 2020-2021. Health-related quality of life (HRQoL) at 6 months was measured using the generic EuroQoL 5-dimension 5-level (EQ-5D-5L) instrument. Pre-specified subgroup analyses examined age (arbitrary cut-off 65 years) and duration of IMV (arbitrary cut-off 72 h). A total of 210 patients were analysed (remifentanil n = 104; fentanyl n = 106). Opioid acquisition costs were comparable between groups. Total mean hospital bed-day costs were lower in the remifentanil group compared with the fentanyl ($48,301 [$38,644-$57,958] vs. $37,012 [95% confidence interval {CI}: $27,834-$46,191]; p = 0.006). The remifentanil group was associated with lower total hospital costs in older patients (≥65 years) and in those ventilated for ≤72 h. At 6 months, 110 patients were alive, with 7 lost to follow-up, (61/103 remifentanil [59.2%] vs. 59/100 fentanyl [59.0%]; p = 0.80). Among survivors, remifentanil continued to demonstrate lower overall hospital costs, but 6-month HRQoL remained similar between groups (EQ-5D-5L index 0.83 vs. 0.87; p = 0.24). Remifentanil was associated with lower total hospital costs than fentanyl, without differences in survival or HRQoL at 6 months, suggesting that remifentanil may be a lower-cost alternative for analgosedation. However, the results are exploratory and require confirmation in larger, adequately powered multicentre phase-2 trials.
Cartilage defects remain a major clinical challenge due to the limited efficacy of current therapies and the intrinsically low regenerative capacity of chondrocytes. Mechanical loading has emerged as a promising strategy to enhance stem cell-based cartilage repair; however, the underlying molecular mechanisms remain poorly understood. Here, we show that cyclic tensile strain primes mesenchymal stem cells (MSCs) to secrete exosomes enriched in microRNA-330-3p (miR-330-3p), which markedly enhances cartilage regeneration. Mechanistically, miR-330-3p restores mitochondrial quality control in chondrocytes by engaging an FKBP4-FoxO3a-dependent mitophagy program, leading to activation of PINK1/Parkin-mediated mitochondrial clearance. The regenerative efficacy of miR-330-3p-enriched exosomes was validated in a Sprague-Dawley rat model of cartilage defects. In vitro, miR-330-3p promotes chondrocyte proliferation and migration while suppressing apoptosis, senescence, and extracellular matrix degradation. Together, these findings identify mechanically primed MSC-derived exosomes as a mechanistically informed therapeutic strategy for cartilage repair.
In the fat grafting procedure, the new European Regulations and the necessity to perform minimal manipulation processing require the verification of security and performance levels of each device and, in this particular context, functional and tissue responses. The aim of this study is to evaluate the integrity of adipocytes and adipose-derived stromal/stem cells (ADSCs) after their processing using two new mechanical devices operating with a closed system. In this study, two new fat processing systems were assessed. We also considered the biological results of the processing and compared them with the results obtained from Coleman's procedure, the golden standard procedure in fat processing. Histological evaluations revealed the preservation of the fat morphology after both processing types, with similar cellular yields of the extracted ADSCs. The adopted techniques enable the isolation of ADSCs with robust differentiation potential toward adipogenic, chondrogenic, and osteogenic lineages. Furthermore, adipose tissue samples exhibit high efficiency in extracellular vesicle secretion, indicating a promising potential for therapeutic and regenerative applications. The results suggest that the new systems allow the preservation of fat morphology, stemness, and regenerative potential. The novel processing technique proposed by the authors consists of a closed-loop mechanical system that combines continuous filtration and emulsification of adipose tissue through saline washing, aimed at removing biological debris and residual pharmacological agents.
Lower trapezius tendon (LTT) transfer can restore shoulder function, particularly active external rotation (ER) following massive rotator cuff tear (MRCT). However, the optimal graft type and its transfer location on the greater tuberosity remain unclear. To investigate the optimal graft type and location in LTT transfer for posterosuperior MRCT from a biomechanical perspective. Controlled laboratory study. Eight fresh-frozen cadaveric shoulders were tested on a shoulder simulator. LTT transfer was performed with an Achilles tendon fixed over the superior-middle facets (LTT-Achilles), a semitendinosus (ST) tendon to the superior facet (LTT-ST-S), or to the middle facet (LTT-ST-M). A 24-N load was applied to each transferred graft. Under each condition (intact rotator cuff, MRCT, LTT-Achilles, ST-S, and ST-M), humeral head translation and functional abduction force (FAF) were evaluated at 0°, 30°, and 60° of glenohumeral elevation. ER torque was assessed across 5 angles (60° internal rotation [60IR], 30° internal rotation [30IR], neutral, 30° ER [30ER], and 60° ER [60ER]) at 0°, 30°, and 60° of glenohumeral elevation. None of the LTT conditions significantly depressed humeral head posterosuperior migration as compared with MRCT. Compared with MRCT, FAF improved significantly with LTT-Achilles at 0° elevation (P = .014) and LTT-ST-S at 0° (P < .001) and 30° elevation (P = .003). LTT-ST-M improved ER torque compared with MRCT at 0° elevation (60IR, P = .04; 30IR, P = .02; neutral, P = .007; 30ER, P = .03; 60ER, P = .006) and at 30° elevation (60IR, P = .01; 30IR, P = .02; neutral, P = .006). LTT-ST-M showed higher ER torque than both LTT-Achilles and LTT-ST-S at 0° elevation (30IR [LTT-Achilles, P = .03; LTT-ST-S, P = .04]; neutral [LTT-Achilles, P = .02; LTT-ST-S, P = .007]). In LTT transfer for MRCT, LTT-ST-M most effectively restored ER torque, whereas LTT-Achilles and LTT-ST-S improved FAF. None of the conditions of LTT transfer suppressed humeral translation. Graft selection and transfer location in LTT transfer can be tailored to patient goals and graft availability, leading to a more patient-specific surgical strategy.
Multiple factors influence the efficacy of mechanical thrombectomy (MT) in patients with acute ischemic stroke. This study aimed to clarify the association between admission hyperglycemia (AH) and long-term functional outcome and to determine whether this association is mediated by postoperative renal function. A total of 397 patients with acute ischemic stroke who underwent MT between February 2018 and June 2024 and had available 6-month follow-up were included in this study. Functional outcome was assessed using the modified Rankin Scale (mRS), with scores of 0-2 indicating a good outcome. Multivariable regression models were constructed, adjusting for relevant covariates, including diabetes and the diabetes × AH interaction term. Mediation analysis was performed to explore the mediating effect of postoperative renal function. Among the 397 patients, the median postoperative estimated glomerular filtration rate (post-eGFR) was 92.4 mL/min/1.73 m2 (IQR: 76.2-106.3), 198 (49.9%) patients had AH, and a good outcome at 6 months was achieved in 151 (38.0%) patients. After adjustment for confounding factors, multivariable regression analysis demonstrated that AH [OR (95% CI): 3.148 (1.672-5.925), p < 0.001] and lower post-eGFR [OR (95% CI): 0.978 (0.963-0.993), p = 0.004] were significantly associated with a lower likelihood of a good outcome at 6 months. Mediation analysis showed that post-eGFR mediated the association between AH and good prognosis, accounting for 25.57% of the total effect. Our study suggests that admission hyperglycemia is independently associated with long-term functional outcome after MT in patients with acute ischemic stroke, with or without diabetes. This association may be partly mediated by postoperative renal function.
Glutaraldehyde (GA) fixation of pericardial tissue is widely used in bioprosthetic heart valves. However, how GA concentration and incubation time jointly influence structure-function relationships remains incompletely understood. This study systematically evaluates the effects of GA concentration and incubation time on collagen architecture and mechanical behavior in human pericardial tissue. Human pericardium was treated with GA concentrations of 0%-2.5% for 5-90 min. Collagen structure was quantified using Picrosirius red imaging and image analysis, while mechanical behavior was assessed via strain-controlled uniaxial tensile testing. Increasing incubation time was associated with reduced collagen waviness and evidence of fiber bundling. Mechanical analysis revealed a significant interaction between GA concentration and incubation time for maximum strain and transition strain (p < 0.05), indicating a non-linear, non-additive treatment effect. Repeated-measures correlation analysis showed strong internal consistency among mechanical parameters (e.g., maximum stress vs. high-strain modulus, rrm = 0.92), whereas structural descriptors such as waviness and fiber orientation exhibited minimal association with mechanical outcomes (rrm = 0.06). GA treatment effects arise from a coupled, non-additive interaction between concentration and incubation time rather than a simple dose-response relationship. Importantly, commonly used structural metrics do not directly predict mechanical performance, underscoring the need for integrated structure-function assessment. These findings provide a framework for future evaluation of GA-treated pericardium in bioprosthetic applications.
Volumetric muscle loss (VML) poses a significant challenge due to the limited regenerative capacity of skeletal muscle. In this context, emerging four-dimensional (4D) regenerative strategies, which couple biomimetic scaffolds with external dynamic stimuli, have gained increasing attention for their potential to enhance repair outcomes. A novel piezoelectric scaffold based on egg white proteins (EWP) integrated with barium titanate (BTO) particles was developed using a rapid and versatile microwave-assisted method. The optimized EWP:BTO 1:1 scaffolds combine favourable porosity, mechanical compliance, and controlled degradation, closely mimicking native muscle tissue. Corona poling imparts permanent polarisation to the BTO phase, enabling localised electromechanical stimulation under ultrasound. C2C12 myoblasts cultured on these scaffolds exhibited enhanced adhesion, proliferation, infiltration and differentiation. Ultrasound stimulation synergized with polarisation to upregulate early mechanosensitive and electroactive genes. These findings highlight the capacity of piezoelectric scaffolds to integrate structural and dynamic cues, an essential feature of 4D scaffold-based approaches, promoting early myogenic signalling. A pilot in vivo study confirmed biocompatibility and structural integrity over 28 days, with no evidence of local or systemic toxicity, supporting the suitability of the scaffold for further evaluation in VML models. Overall, EWP:BTO 1:1 piezoelectric scaffolds constitute a sustainable, biocompatible, and functionally active 4D platform that converts mechanical energy into targeted electrical cues. By coupling biomimetic architecture with ultrasound-driven electromechanical activation, this approach provides a versatile and non-invasive strategy to modulate muscle regeneration and represents a promising platform for future functional muscle regeneration studies in VML.
Tissue turnover depends on the efficient removal of damaged cells to maintain structural and functional integrity. Cells respond to damage across a spectrum of outcomes, ranging from repair and recovery to senescence, apoptosis, and malignant transformation. This review focuses on apoptosis and senescence in epithelia as two outcomes with profound consequences for tissue homeostasis, one ensuring swift mechanical removal of damaged cells and the other driving persistent tissue disruption. While apoptotic cells are efficiently eliminated through coordinated mechanical processes, senescent cells resist elimination and progressively impair tissue function through chronic inflammation and mechanical remodeling of the tissue microenvironment. Restoring tissue function therefore requires strategies to efficiently clear or reverse the senescent state. Immune-mediated clearance and senolytic drugs can reduce senescent cell burden, yet their efficacy and selectivity remain limited. Emerging mechanobiological strategies, including low-frequency ultrasound and geometric confinement, offer a complementary approach by directly reversing the senescent phenotype through physical cues. Ultimately, harnessing these mechanical forces offers a promising avenue toward restoring tissue function.
Identifying the drivers of cellular senescence that contribute to the decline in vascular function with age and disease is critical for developing restorative interventions. Here, we investigated how increased mechanical stress from extracellular matrix (ECM) stiffening shapes endothelial cell (EC) senescence. We developed a 3D human in vitro model that decouples mechanical stress from inflammatory or biochemical signals, enabling the study of senescence responses to tissue stiffening alone. We found that matrix stiffening induces an EC senescence phenotype with elevated p16/p21 and an immunomodulatory senescence-associated secretory phenotype (SASP), in the absence of inflammatory signals. This mechano-induced senescence activates Notch signaling, and treatment with an FDA-approved γ-secretase inhibitor attenuates stiffness-induced senescence. Analysis of fibrotic capsule tissue from patients with synthetic breast implants, a model of localized, mechanically driven fibrosis, validated an increase in p16+Notch1+ endothelial populations. Complementary single-cell RNA sequencing data further confirmed enrichment of Notch- and SASP-related gene programs. Our work provides a human-relevant platform for studying targetable stages of endothelial mechanoaging and identifies potential therapeutic targets associated with stiffness-induced endothelial senescence for mechanically remodeled tissues.
Finite element analysis (FEA) is a widely used method to evaluate the biomechanical aspects of dental implants; however, its clinical reliability depends on experimental validation. With the introduction of three-dimensional (3D) printing, customized implants offer potential improvements in stress distribution. The study was done to evaluate and compare stress distribution in conventional and 3D-printed implant models using FEA. An experimental research was done with a sample size of 480 observations. 3D implant models were developed and analyzed using ANSYS Workbench under simulated loading conditions (100-150 N). An in vitro validation was performed using strain gauges under mechanical loading. Statistical analysis was conducted using IBM SPSS version 25.0 with P < 0.05. The 3D-printed implant models demonstrated significantly lower stress values across all regions, particularly at the crestal bone. In vitro strain values were also reduced in the 3D group. A strong positive correlation was found between FEA and experimental findings (r = 0.872, P = 0.001). 3D-printed implants exhibit improved biomechanical performance with reduced stress concentration and strong validation of FEA outcomes. Résumé Introduction:L’analyse par éléments finis (AEF) est une méthode largement utilisée pour évaluer les aspects biomécaniques des implants dentaires; cependant, sa fiabilité clinique dépend d’une validation expérimentale. Avec l’introduction de l’impression tridimensionnelle (3D), les implants personnalisés offrent des améliorations potentielles en matière de distribution des contraintes. Cette étude a été réalisée afin d’évaluer et de comparer la distribution des contraintes dans des modèles d’implants conventionnels et imprimés en 3D, à l’aide de l’AEF.Matériels et Méthodes:Une recherche expérimentale a été menée sur un échantillon de 480 observations. Des modèles d’implants 3D ont été développés et analysés à l’aide d’ANSYS Workbench sous des conditions de charge simulées (100–150 N). Une validation in vitro a été réalisée à l’aide de jauges de contrainte sous charge mécanique. L’analyse statistique a été effectuée à l’aide d’IBM SPSS version 25.0 avec un seuil de signification de P < 0,05.Résultats:Les modèles d’implants imprimés en 3D ont démontré des valeurs de contrainte significativement plus faibles dans toutes les régions, en particulier au niveau de la crête osseuse. Les valeurs de déformation in vitro étaient également réduites dans le groupe 3D. Une forte corrélation positive a été observée entre les résultats de l’analyse par éléments finis (FEA) et les données expérimentales (r = 0,872, P = 0,001).Conclusion:Les implants imprimés en 3D présentent des performances biomécaniques améliorées, avec une concentration de contraintes réduite et une forte validation des résultats de l’analyse par éléments finis.
Our overall aim was to assess the sustainability of exploitation of slow-growing, long-lived intertidal Ascophyllum nodosum forests. They have been mechanically harvested for almost 50 years in Breiðafjörður, Iceland, but there is a lack of long-term local research as various local factors can impact the recovery time of Ascophyllum. Post-harvest studies of the Ascophyllum stands are important for understanding recovery, particularly re-growth of fronds on individual plants and population structure of the resource to inform management. At four sites, we demarcated two control plots and one harvest plot which was mechanically harvested by the local seaweed harvesting team. Biomass and cover of all fucoids and plant height of Ascophyllum plants were measured on shore transects from 2016 to 2021. Ascophyllum harvesting was most efficient in the middle and lower parts of its zone on the shore due to tidal and mechanical constraints of cutters on the upper shore. Efficiency of the harvesting at mid and low shore ranged from 35% to 66% biomass removal at sites where harvesting effort was measured. Ascophyllum reached pre-harvest cover within 3 years at all sites. Ascophyllum biomass recovered within 5 years at all sites; but pre-harvest plant height had not been reached within the 5-year study period. Harvesting efficiency varied among the four sites due to variability in shore topography. Despite the large biomass removed, it was difficult to distinguish between the effect of harvesting and occasional disturbance events such as storms. We confirmed the efficacy of rotation of harvesting on a 5-year cycle. Sustainable stewardship of Ascophyllum benefits from the complex topography of Icelandic shores leading to refuges from cutting, coupled with rotation among shores.
Spinal cord injury (SCI) disrupts neural circuits and creates an inhibitory microenvironment, posing challenges such as low cell survival rates and limited host integration for traditional cell transplantation therapies. This study developed an injectable, self-adaptive, and self-repairing oxidized hyaluronic acid-carboxymethyl chitosan (OHA-CMCS) dual-network interpenetrating hydrogel. This hydrogel serves as a functionalized, dynamically responsive cell-matrix co-delivery platform for delivering spinal cord-specific V3 neuronal precursors derived from human pluripotent stem cells. Through tissue-mimetic mechanical design, the hydrogel closely simulates the spinal cord tissue microenvironment. Its reversibly crosslinked network exhibits excellent compliance and self-healing capabilities, forming bidirectional feedback coupling with V3 cells across mechanical and biochemical dimensions, thereby significantly enhancing cell survival and functional maturation. In rats with complete spinal cord transection, the "material-cell synergistic system" (OC0.33+V3) formed by the OHA-CMCS hydrogel and V3 cells markedly improved motor function (BBB score, grip strength, gait analysis) and remodeled the injured microenvironment. Mechanistic studies reveal that this system drives microenvironmental reprogramming through material-cell interactions, inhibiting glial scar formation, inducing M2 polarization of microglia, and promoting axonal regeneration and vascular remodeling. Chemogenetic validation further confirms that transplanted V3 neurons successfully integrate into host neural circuits and exert inhibitory regulatory functions. This study proposes a dual-engine strategy of "material-driven regulation and cell-function integration," revealing the mechanism by which biomimetic hydrogels synergize with neurons to repair spinal cord injury, establishing a new paradigm for intelligent neuroregeneration systems.
Alzheimer's disease (AD) is usually framed as a proteinopathy and network disorder, but this view may be incomplete. We propose a mechanobiological hypothesis in which synaptic micromechanics, regional brain softening, vascular pulsatility, and glymphatic transport are parts of a coupled fluid-solid system whose failure contributes to AD progression. In this framework, early synaptic and glial mechanical fragility reduces the capacity of vulnerable circuits to maintain stable structure, efficient signaling, and waste clearance, while age-related tissue softening and impaired perivascular transport amplify amyloid and tau accumulation, network dysfunction, and cognitive decline. This framework integrates converging evidence from dendritic spine to glymphatic system biology, concordant results obtained with diffusion MRI and magnetic resonance elastography, and treats altered tissue mechanics not merely as a correlate of degeneration but as a potentially active multicomponent of disease expression. It further predicts that biomechanical alterations should be detectable before gross atrophy, should covary with glymphatic impairment, and may help explain why molecular pathology and clinical symptoms are often only partly aligned. By positioning brain mechanics as an interface between protein aggregation, synaptic dysfunction, and impaired clearance, this framework identifies testable imaging biomarkers and suggests potential early-stage intervention strategies aimed at preserving tissue resilience as well as reducing pathological protein burden.
Embryonic scaling is the ability of developing embryos to preserve proportional patterning despite differences in overall size. This phenomenon has long been recognized in many animal groups and represents a central example of developmental robustness and self-regulation. Its mechanisms are now being clarified through quantitative embryology, theoretical modeling, molecular developmental biology, and mechanobiology. The best-characterized framework for understanding embryonic scaling is morphogen-gradient scaling. In this view, pattern proportions are preserved when morphogen gradients adjust their range and threshold positions according to the size of the embryo or morphogenetic field. Several mechanisms can contribute to this adjustment, including feedback regulation within morphogen networks, size-dependent morphogen production or degradation, ligand transport, and mechanical or geometric constraints. Earlier theoretical studies anticipated the possibility that morphogen-gradient scaling may require size-dependent modulators, that is, regulatory components whose concentration or activity changes with system size. This review considers such size-dependent regulation in the context of the Scalers Hypothesis, which focuses on experimentally identifiable genes and proteins whose expression, concentration, or activity changes systematically with embryo size. Their products can therefore act as molecular links between global geometry and local patterning dynamics. In this way, they may adjust morphogen production, degradation, transport, diffusion range, or threshold interpretation in a size-dependent manner. The review places scaler genes within a broader comparative framework that includes Drosophila BMP/Dpp-Sog and Bicoid systems, chick blastoderm regulation, mechanical models of epithelial patterning, and regenerative or synthetic systems such as Hydra, planarians, and gastruloids. It then distinguishes between internal scalers, which are embedded within morphogenetic feedback networks such as BMP-Chordin and Nodal-Lefty systems, and external scalers, whose regulation is independent of the core pattern-forming circuitry. Finally, the review summarizes experimental evidence from amphibian and echinoderm embryos showing that matrix metalloproteinase Mmp3 in Xenopus laevis and the astacin-like proteases Span and Bp10 in sea urchins function as external scalers required for size-dependent adjustment of BMP-Chordin gradients. These findings support a modular view of embryonic scaling, in which size sensing and pattern generation may be partially separable. They also suggest practical strategies for identifying size-dependent regulators in other embryos, organ primordia, regenerative systems, and engineered multicellular models.
Unstable pelvic ring fractures are associated with life-threatening haemorrhage and mortality rates of 20-40%, requiring rapid and coordinated management. This narrative review synthesises the current evidence for haemorrhage control and definitive fixation strategies in haemodynamically unstable pelvic fractures, encompassing early mechanical stabilisation (pelvic binders, external fixation), pre-peritoneal pelvic packing (PPP), angiographic embolisation (AE), and the evolving role of resuscitative endovascular balloon occlusion of the aorta (REBOA), within a unifying damage control orthopaedics framework. Damage control orthopaedics (DCO) provides the conceptual backbone of the management pathway. Early mechanical stabilisation reduces pelvic volume and re-establishes tamponade; PPP extends this tamponade surgically; and AE provides targeted definitive control of arterial bleeding. These techniques are complementary, not competing, and are integrated in sequence guided by patient physiology and bleeding source. Accumulating evidence from randomised and registry-based studies has raised important questions about routine REBOA deployment - current high-quality evidence, including the UK-REBOA Randomised Clinical Trial, has not demonstrated a survival advantage over standard care, and registry data have raised concerns regarding potential harm in isolated pelvic fractures; however, these findings should be interpreted in the context of the predominantly retrospective and heterogeneous evidence base across this field. Once haemorrhage is controlled and physiology restored, definitive fixation of the pelvic ring - timed according to DCO principles - restores structural stability, enables early mobilisation, and improves long-term functional outcomes. Optimal care requires integration of surgical, endovascular, and orthopaedic strategies within protocol-driven, multidisciplinary trauma systems.
Guillain-Barré syndrome (GBS) is an autoimmune polyradiculopathy linked to various triggers. Recently, several case reports described GBS development following intracranial hemorrhage (ICH), posing diagnostic and therapeutic challenges. PubMed and EMBASE were searched from inception till February 2023 for case reports. Two reviewers independently screened the articles and extracted data using a standardized form. The extracted data were then analyzed narratively. Quality was assessed with the JBI Checklist for Case Reports. Twenty-three cases from 11 countries were identified (14 males, mean age of 60.1 years). Onset of GBS occurred after a median of 9 days (range 2-24) post-ICH, with intracerebral hemorrhage being the most common antecedent (39.1%), followed by subarachnoid (26.1%) and subdural hemorrhage (21.7%). Electrophysiology showed predominantly axonal variants, while CSF consistently demonstrated albuminocytologic dissociation with positive antiganglioside antibodies in five cases. The clinical course was severe, marked by rapid progression to nadir (median 2.5 days), profound functional impairment (average Hughes Functional Grading Scale: 4.57 ± 0.66), and a high rate of respiratory failure requiring mechanical ventilation (78.3%). Axonal variants were associated with higher rates of mechanical ventilation and poorer outcomes than demyelinating forms. Among the 21 patients who received immunomodulatory treatment, 3 (14.3%) showed complete recovery, 13 (61.9%) had partial recovery, 3 (14.3%) had a poor recovery, and 2(9.5%) died at last follow up. GBS may complicate recovery after ICH and appears to present with an aggressive course, particularly in axonal variants. Clinicians should consider GBS when patients with ICH develop progressive, symmetrical weakness unexplained by the initial brain injury, as prompt initiation of immunotherapy may improve outcomes.
Three-dimensional (3D) cell culture systems are increasingly recognised as more physiologically relevant models than traditional two-dimensional cultures, as they better mimic the native tumour microenvironment and enable the study of complex cellular behaviour. However, applying atomic force microscopy (AFM) to these models is challenging due to the inherent instability of multicellular aggregates, which complicates reproducible mechanical property measurements. To address this, we developed and evaluated two distinct strategies for confining multicellular aggregates for AFM analysis. In the first approach, aggregates were encapsulated in porous 3D-printed truncated conical microstructures fabricated by two-photon polymerisation. These structures were designed to allow medium perfusion, which is hypothesised to improve nutrient and metabolite exchange by enhancing fluid accessibility within the confined environment. In the second, cylindrical cavities were microfabricated into the base of PolyHEMA-coated Petri dishes to provide a simple yet robust platform for aggregate retention. Both methods successfully confined aggregates without compromising cellular integrity, enabling reproducible and reliable measurements of stiffness and viscoelasticity. Human pancreatic cancer cells (PANC-1) were used both as single cells and as monotypic aggregates. Aggregates confined in either system were consistently softer than substrate-attached single cells, indicating reduced cytoskeletal tension and altered remodelling in 3D environments. Among the two approaches, cylindrical cavities provided more reliable aggregate retention, whereas the 3D-printed truncated conical structures may possibly facilitate improved medium access through their porous architecture. Together, these microconfinement strategies enable reproducible mechanical characterisation of multicellular aggregates and extend the applicability of AFM to tumour mechanobiology and the assessment of anticancer therapies.
Magnesium-based implants are increasingly investigated as bioabsorbable materials for temporary osteosynthesis applications due to their favorable biocompatibility and bone-like elastic modulus. However, controlling the degradation rate remains a critical barrier to clinical translation, as rapid corrosion can compromise mechanical integrity and lead to adverse effects, such as gas formation. PEO-modified WE43MEO (WE43-PEO) and non-modified WE43MEO screws and plates were implanted in the humerus and femur of Göttinger minipigs in a non-fracture model and assessed after 18 months. Explants were analyzed using micro-computed tomography and non-decalcified histology with histomorphometric quantification of residual implant structure and peri-implant bone response. No significant differences in cortical implant volume were observed. However, PEO modified implants were surrounded by significantly higher volumes of lamellar bone, suggesting reduced remodeling and improved bone integration. Non-modified WE43MEO implants underwent complete degradation, while PEO modified implants showed partial resorption with preserved structure, indicating effective degradation control. Both implant types remained integrated without long-term complications. PEO surface modification of WE43 magnesium implants supports predictable, biocompatible long-term degradation and promotes favorable bone quality without late complications, underscoring the potential of surface-engineered magnesium fixation devices for load-bearing applications. PEO-modified WE43MEO osteosynthesis systems may offer clinically relevant, bioabsorbable fixation with controlled degradation and improved long-term bone integration, potentially reducing implant-related complications and the need for secondary removal procedures in orthopaedic and craniomaxillofacial surgery.