Journals
2026 EN
Tetteh Abigail E. · Smith James A. · Porter Daniel A.
+2 more
ABSTRACT Additive manufacturing (AM) can create orthopedic devices with integrated porosity that enables bone fixation post‐implantation. While porosity is key in promoting bone ingrowth and long‐term fixation, the device must provide adequate mechanical strength and functionality. Since AM process parameters dictate the final mechanical performance of printed parts, identifying key process parameter levels that preserve or improve such behavior in load‐bearing devices with integrated porosity is essential. Using a Taguchi design of experiments, gyroid‐structured polyether‐ether‐ketone (PEEK) and polyether‐ketone‐ketone (PEKK) specimens were fabricated via fused filament fabrication (FFF) AM to examine the impact of nozzle temperature ( T N ), chamber temperature ( T Ch ), and layer height (LH) on their compressive mechanical behavior. In addition to compression testing, the printed specimens were analyzed using optical microscopy, scanning electron microscopy, and micro‐computed tomography. Elevated processing conditions, specifically high T Ch combined with thick LH, can enhance heat retention, slow crystallization, increase strut thickness, and improve bonding at strut junctions, enabling porous PEEK and PEKK to withstand higher compressive loads. The elastic moduli of all the porous specimens were more sensitive to variations in processing conditions than their yield strength. Notably, the more amorphous PEKK specimens achieved over 87%–88% of PEEK's calculated elastic modulus in this study and 87%–90% of the yield strength without undergoing annealing. These results are promising, considering that, like PEEK, the elastic modulus of the porous PEKK fell within the range of trabecular bone, while its yield strength surpassed that of trabecular bone.
Journals
2026 EN
MojicaSantiago Jorge A. · Agarwal Gopal · RoblesBlasini Steven
+6 more
ABSTRACT In this study, we describe the gelation kinetics, cytocompatibility, and mechanical properties of interpenetrating networks of collagen (COL), fibrin (FIB), hyaluronan (HA), and laminin (LAM) to evaluate their potential to produce mature skeletal muscle tissue. Skeletal muscle is a dynamic tissue that relies on the fusion of myoblasts into multinucleated myofibers to maintain homeostasis. In progressively degenerative conditions, impaired myoblast fusion leads to skeletal muscle atrophy and significant mass loss. Three‐dimensional (3D) in vitro models for skeletal muscle disease have been developed to better understand disease mechanisms and facilitate drug screening. However, most rely on Matrigel, a tumor‐derived matrix that supports robust cell growth but has limited clinical relevance. To address this limitation, we focused on creating natural, multi‐component scaffolds specifically tailored for muscle applications with clinically relevant drug testing use. Using spectrophotometry and rheology, we characterized the gelation kinetics and viscoelastic properties of interpenetrating networks with varying mass ratios of COL to FIB, supplemented with fixed proportions of HA and LAM. Tunable gelation was achieved within a range of 10 to 16 min. Cytocompatibility studies with C2C12 murine myoblasts demonstrated favorable cell viability in 1:1 and 1:2 (w/w) COL:FIB blends incorporating HA and LAM. Immunostaining of differentiated C2C12 cells confirmed Myosin 4 Monoclonal Antibody (MF‐20) expression in these blends when seeded into polydimethylsiloxane (PDMS)‐anchored bundles. Notably, in cell‐laden 1:1 COL:FIB gels with a seeding density of 10 × 10 6 cells/mL, the compressive modulus increased three‐fold between days 4 and 7 of differentiation. These findings highlight the potential of COL:FIB interpenetrating networks, enhanced with HA and LAM, as promising scaffolds for developing clinically relevant models of skeletal muscle tissue.
Journals
2026 EN
Bandara Geshani C. · Boudreau Ryann D. · Wyatt William
+1 more
ABSTRACT Biomaterial‐based skeletal muscle tissue engineering approaches have largely focused on mimicking the 3D aligned architecture of native muscle, which is critical for guiding myotube formation and force transmission. In contrast, fewer studies incorporate glycosaminoglycan (GAG)‐mediated biochemical cues despite their known role in regulating myogenesis and growth factor sequestration. In this study, we develop aligned collagen‐GAG (CG) scaffolds using directional freeze‐drying and systematically vary GAG type by incorporating GAGs of increasing sulfation levels (hyaluronic acid, chondroitin sulfate, and heparin). While all scaffold variants support myoblast adhesion, metabolic activity, and myotube alignment, heparin‐modified CG scaffolds significantly enhance myoblast metabolic activity and myogenic differentiation as measured by myosin heavy chain (MHC) expression and myotube size. We additionally show that heparin‐modified scaffolds sequester and retain significantly higher levels of insulin‐like growth factor‐1 (IGF‐1), a potent promoter of myogenesis, compared to other scaffold groups. Together, these results highlight the importance of tailoring GAG type in CG scaffolds for targeted applications and underscore the promise of heparin‐modified CG scaffolds as a material platform for skeletal muscle tissue engineering.
Journals
2026 EN
Ghasemzaie Niloofar · Khader Basel A. · Tran Steven
+5 more
ABSTRACT Tissue‐engineering scaffolds require interconnected porous networks to support cell infiltration, nutrient diffusion, and waste removal. Conventional methods to introduce porosity—such as particulate leaching, gas foaming, and freeze‐drying—can leave cytotoxic residues. We propose a scalable, cytocompatible approach to tune hydrogel porosity using lipid‐shelled gas microbubbles as a transient porogen. In this study, we demonstrate that lipid‐shelled microbubbles can be incorporated into alginate, poly(ethylene glycol) diacrylate (PEGDA), or gelatin methacrylate (GelMA) precursors, and subsequently expanded post‐gelation with mild heat or vacuum to yield controlled porosity. In alginate fibers, the vacuum expansion of embedded microbubbles increased the swelling capacity by approximately 74% relative to nonporous control, without reducing compressive strength. Porous PEGDA hydrogels showed faster degradation (approximately 40% reduction in degradation time) and a lower compressive modulus compared to the dense PEGDA control, reflecting a tunable trade‐off between porosity and stiffness. Unlike traditional porogen‐based or 3D‐printing techniques, this microbubble method requires no toxic additives or specialized equipment and is compatible with both ionic (alginate) and photo‐crosslinked (PEGDA, GelMA) systems. We further demonstrate integration of this approach with a microfluidic fiber production platform. We validate that porosity modulation via microbubbles does not adversely affect the viability of mesenchymal stem cells on GelMA hydrogels. Overall, this work establishes a broadly applicable and easily scaled strategy in which porosity can be tuned post‐gelation with simple triggers (heat or vacuum), enabling application‐specific control of nutrient transport, degradation, and mechanics across multiple biomaterials.
Journals
2026 EN
Sodawalla Husain · Alnajrani Mohammed · Wells Jesse
+4 more
ABSTRACT Currently available in vitro benchtop aneurysm models often lack material characteristics for testing the efficacy of endovascular devices. Specifically, current models do not represent the mechanical instability of giant aneurysms and do not predictably rupture under simulated physiological conditions. Hence, in vitro aneurysm models with biomechanically relevant material properties and a predictable rupture timeframe are needed to accurately assess the efficacy of new medical device treatment options. A 3D‐printed giant aneurysm model was developed that can predictably rupture in 2 h when left untreated under physiological conditions to test hemodynamic effects of endovascular treatments. Aneurysm treatment simulations included flow diverter‐only treatment, flow diverter with synthetic thrombus treatment, and flow diverter with liquid embolic treatment, ran in parallel with untreated controls. The flow diverter only treatment ruptured in 47 (±41) min as compared to 54 (±30) min for controls ( p value = 0.36). The flow diverter with synthetic thrombus treatment ruptured in 22 (±16) min as compared to 19 (±10) min for controls ( p value = 0.71). The flow diverter with liquid embolic treatment ruptured in 61 (±27) min as compared to 35 (±17) min for controls ( p value = 0.16). Utilizing physiological benchtop in vitro models, aneurysm rupture can be repeatedly predicted to test the efficacy of medical device treatments. Further studies will investigate the optimization of the engineered aneurysm dome defect with tunable rupture times based on the measurable pressure and flow effects. These optimized in vitro models could ultimately evaluate aneurysm rupture risk and location after treatment.
Journals
2026 EN
Launey Maximilien E. · Bobo Trey · Miri Behnood
+6 more
ABSTRACT Transcatheter cardiovascular devices require high‐purity Nitinol materials with exceptional fatigue resistance to meet stringent Class III regulatory durability requirements. Ultra‐clean VAR/EBR (Vacuum Arc Remelt/Electron Beam Remelt) Nitinol represents a metallurgical advancement that achieves unprecedented control over inclusion size and distribution. This study characterizes the fatigue behavior of VAR/EBR Nitinol with nominal inclusion sizes below 10 μm under conditions representative of transcatheter mitral valve replacement (TMVR) applications, using the HighLife Mitral Valve Replacement system as a clinical case study. Diamond‐shaped fatigue specimens were manufactured from ultra‐clean VAR/EBR Nitinol tubing used in the HighLife Mitral Valve Replacement system and tested under physiologically relevant conditions to 10 7 , 10 8 , and 4 × 10 8 cycles. Testing included multiple combinations of mean strains (1.5%–9%) and strain amplitudes (0.50%–2.50%) to simulate the multi‐strain operating environments encountered in TMVR devices. VAR/EBR Nitinol demonstrated a conservative 130% improvement in 4 × 10 8 ‐cycle Fatigue Strain Limit (FSL) compared to conventional VAR Nitinol at mean strains between 3% and 5%. The FSL behavior revealed two distinct strain regimes correlating with stress‐induced martensitic transformation. Fractographic analysis confirmed elimination of inclusion‐initiated fatigue failure, with crack initiation occurring independently of microstructural defects. The ultra‐clean microstructure of VAR/EBR Nitinol enables a fundamental shift from flaw‐dominated to stress‐dominated fatigue behavior, providing unprecedented safety margins for complex transcatheter devices operating across diverse mechanical conditions. This material advancement has broad implications for Class III cardiovascular device design, enabling devices like the HighLife system and other TMVR platforms to meet stringent regulatory durability requirements while maintaining safety across complex multi‐strain operating environments.
Journals
2026 EN
Sun Steven · Nikanjam Mina · Mirochnick Mark
+9 more
Abstract Bictegravir is an integrase strand transfer inhibitor available in fixed‐dose combination with emtricitabine and tenofovir alafenamide for HIV treatment. The objectives of this study were to develop a population pharmacokinetic model for bictegravir during pregnancy and postpartum, identify main drivers of between‐subject variability, and evaluate the role of adherence patterns in maintaining therapeutic exposure. Intensive bictegravir concentration–time data were used from IMPAACT 2026, a pharmacokinetic study of selected antiretroviral drugs during pregnancy and postpartum. Five hundred and eight bictegravir plasma concentrations from 27 participants during the second and third trimesters of pregnancy and postpartum were utilized for model development. A one‐compartment structural model best described bictegravir PK. Pregnancy increased bictegravir apparent clearance (CL/F) by 61% compared to postpartum, while Black/African American race was associated with a 32% increase in apparent volume of distribution (Vd/F). Plasma albumin concentrations were associated with a 43% decrease in CL/F and body weight was associated with a 120% increase in Vd/F over the range of observed values. Monte Carlo simulations predicted median (90% prediction interval) pre‐dose bictegravir concentrations of 920 ng/mL (265–2081) during the third trimester and 3399 ng/mL (1423–6391) postpartum, exceeding the protein‐adjusted 95% effective concentration (162 ng/mL). Adherence simulations predicted a single missed dose at steady‐state during the third trimester results in 43.7% of virtual subjects with concentrations below pharmacodynamic target, while two consecutive missed doses result in 90.4% with concentrations below target. These results show that while standard bictegravir dosing is effective during pregnancy, consistent adherence is critical to maintain effective therapeutic exposures.
Journals
2026 EN
Heymsfield Steven B. · Hu Houchun H. · Johanssen Edvin
+5 more
ABSTRACT Skeletal muscle (SM) is an integral organ component in the pathophysiology of many acute and chronic diseases. But is there a ‘gold’ standard or accepted reference method for quantifying the amount and composition of human SM mass? Exploring that question led us to recognize the existence of a SM measurement paradigm that divides methods into two broad categories, in vitro and in vivo. In vitro methods quantify SM mass, weighing intact muscles as part of whole cadaver evaluations, only 51 of which are reported in medical literature with no recent additions. In vivo methods are used to evaluate SM in vivo, and two tiers were revealed in our analyses. An upper tier that included three methods considered ‘reference’ approaches for their accuracy and precision: computed tomography, magnetic resonance imaging and dual‐energy X‐ray absorptiometry. A lower in vivo method tier included bioimpedance analysis, three‐dimensional imaging, several approaches involving creatine metabolism, ultrasound and anthropometry. A feature common to all of the lower tier methods is their need for calibration or validation against reference approaches in the upper in vivo method tier. A critical review of the three in vivo reference methods in the upper tier revealed widely variable SM volume/mass acquisition protocols, image analysis methods and applied terminology. Some reports espouse an upper tier reference method as the ‘gold’ standard while providing minimal details of exactly how and what was measured, thus making replication in follow‐up studies difficult. Any technical issues related to an in vivo reference method are propagated to the in vivo methods in the lower tier that are calibrated or validated against them. Our review of in vivo reference methods of quantifying SM mass and composition led us to two broad recommendations. First, published reports including these reference methods should provide enough details related to acquisition and analysis protocols so that readers can replicate their findings. Second, an effort should be made to apply precise terminology in published reports in order to avoid confusion on exactly what was measured; suggestions are made on definitions of commonly used terms when referring to body composition compartments. Lastly, because there is no consensus on what constitutes a ‘gold’ standard for SM measurement, we suggest expert groups convene in the future to recommend optimum approaches and working guidelines for quantifying muscle mass and composition in vivo.
Journals
2026 EN
Zheng Yaochao · Jurgielewicz Brian Joseph · Helton Leah G
+4 more
ABSTRACT The interaction between mutated leucine‐rich repeat kinase 2 (LRRK2) and the death adaptor protein FADD accounts for apoptotic death of dopaminergic neurons in familial Parkinson's disease (PD) driven by LRRK2 mutations. Disrupting this pathogenic interaction using constrained peptides is a promising therapeutic strategy to mitigate apoptotic neuronal death in PD. However, efficiently delivering these therapeutic peptides to disease‐relevant cells within the central nervous system (CNS) remains challenging due to degradation in circulation and poor blood‐brain barrier and cell membrane penetration. Here, we present a strategy to use extracellular vesicles (EVs) as delivery vehicles for the therapeutic peptides to enhance their cellular uptake and CNS targeting. Following an optimized passive loading approach, we successfully packaged these peptides into EVs, improving their cellular uptake by disease‐relevant neural cells in vitro and brain biodistribution in mice following intravenous administration. EV‐based delivery enhanced the therapeutic efficacy of these peptides in disrupting FADD‐LRRK2 interactions, reducing downstream caspase signaling and neuronal death in cellular models of PD compared to the free peptide format. These findings support the use of EVs as a promising shuttle for peptide‐based therapies in PD and potentially other neurological disorders.
Journals
2026 EN
Fernandez Garcia Adriana · Iyer Poorvi · Ashi Pablo
+10 more
ABSTRACT Pediatric high‐grade gliomas (pHGGs) account for 20% of childhood brain tumours and are associated with poor survival. Currently, pHGG detection relies on MRI, a costly and time‐consuming procedure. Extracellular vesicles (EVs) carry molecular markers indicative of their cellular origin and can be isolated from various biofluids, offering an alternative approach. Recent studies showed that pHGGs contain cells that molecularly and morphologically resemble radial glia (RG), a type of neural progenitor. Given that RGs are normally exclusive to the developing brain, we hypothesized that EVs secreted from RG‐like glioma cells serve as a pHGG biomarker. However, there are no established molecular markers to specifically detect RG‐derived EVs. To address this, we first identified a combination of surface markers to differentiate EVs derived from RG‐like glioma cells from those of non‐RG cells. We next validated the expression of these markers in patient‐derived cell lines. Analysis of EVs isolated from cell culture media confirmed the presence of these markers, along with other tumour‐associated markers including targets of chimeric antigen receptor (CAR) T cell therapy. Taken together, our results showed that RG‐derived EVs can be isolated and detected by the combination of markers, laying a groundwork for developing a novel EV‐based biomarker for pHGGs.