Bioactive Materials

Controlled delivery of growth factors and viable cells remains a significant challenge in bone tissue engineering. In this study, a 3D-printed hydrogel scaffold system was developed for the co-delivery of bone morphogenetic protein-9 (BMP-9) and preosteoblasts to enhance bone regeneration. The system consisted of a 3D-printed base scaffold containing BMP-9-coated calcium sulfate (CaS) microparticles and a photocurable hydrogel coating layer encapsulating viable cells. The scaffold design exploited electrostatic interactions between BMP-9 and gelatin matrices by incorporating gelatin type B in the base scaffold and gelatin type A in the coating layer. Differences in the isoelectric points of these gelatin types were utilized to regulate protein binding and release. Release studies demonstrated that CaS microparticles alone exhibited rapid burst release, with nearly 80% of BMP-9 released within 24 h. Encapsulation of BMP-9 coated CaS particles in the 3D-printed scaffolds reduced the release rate, while the addition of the coating layer significantly improved sustained release, limiting BMP-9 release to approximately 50-60% by day 5. Bioactivity studies showed enhanced cell attachment in BMP-9 containing scaffolds compared with controls. Live/Dead cytotoxicity assays demonstrated high cell viability (>80%) within the coating layer over the culture period, confirming that the encapsulation and photocuring processes did not adversely affect cell survival. Cell proliferation and differentiation were further evaluated using WST-1 and alkaline phosphatase assays. The results demonstrate that electrostatic interactions governed by gelatin type selection can regulate BMP-9 release while maintaining high cell viability, providing a promising platform for growth factors and cell delivery in bone tissue engineering.

Central nervous system (CNS) disease or injury might be treated by implanted devices, tissue regenerative scaffolds, or drug delivery platforms. However, inflammatory CNS responses limit these interventions and may worsen outcomes following damage to the CNS. Via the foreign body reaction (FBR), macrophages and glial cells trigger a "glial scar" around implants, reducing device performance, scaffold regenerative ability, or drug delivery potential. Previous studies have shown that stiffness of CNS implants significantly affects glial encapsulation, but few studies have investigated materials that truly match brain tissue stiffness. Porous precision-templated scaffolds (PTS) with uniform, interconnected, 40 {micro}m pores have shown favorable healing outcomes and a reduced FBR in numerous soft and hard tissue applications. To quantify the effects of both hydrogel compliance (stiffness) and pore size on glial encapsulation, we implanted poly(2-hydroxyethyl methacrylate-co-glycerol methacrylate) (pHEMA/GMA) PTS of varying stiffness and pore size for 4 weeks in rat brain. We observed reduced astrocyte encapsulation around PTS compared to solid hydrogel rods, reduced pro-inflammatory macrophage polarization for softer hydrogels versus stiffer hydrogels, and the presence of neuronal markers and neurogenesis within the pores. Utilizing soft, precision-porous hydrogels could provide a strategy for mitigating glial scarring and improving implant-based CNS treatments.

Pancreatic ductal adenocarcinoma (PDAC) remains difficult to treat with nucleic acid therapeutics because efficient intratumoral delivery is limited and off-target liver accumulation is common. Here, we developed a structure-activity map for intraperitoneally administered mRNA lipid nanoparticles (mRNA-LNPs) to identify formulation features that improve delivery to pancreatic tumors while reducing liver expression. A full-factorial library of 48 mRNA-LNP formulations was generated by varying ionizable lipid, sterol, phospholipid, and PEG-lipid components. Formulations were characterized for size, polydispersity, zeta potential, and encapsulation, then evaluated in an orthotopic KPC8060 pancreatic tumor model after intraperitoneal administration of firefly luciferase mRNA-loaded LNPs. Biodistribution was assessed by Rhodamine B fluorescence and functional delivery by luciferase expression 12 h after dosing. Lipid composition strongly influenced both physicochemical properties and in vivo performance. G0-C14-based formulations produced the smallest and most homogeneous particles, whereas FTT5-containing formulations were generally larger. Across the 48-formulation library, mRNA expression and nanoparticle biodistribution varied significantly among tumor, pancreas, liver, and spleen. Statistical, decision-tree, and predictive modeling analyses identified composition rules associated with organ-selective delivery. High tumor expression was associated primarily with G0-C14 combined with DSPC and {beta}-sitosterol, whereas liver expression was favored by C12-200 or DLin-MC3-DMA with DOPE and DSPE-PEG. Notably, a G0-C14/DSPC/DSPE-PEG formulation emerged as a lead candidate, producing a greater than 6-fold increase in tumor luciferase signal relative to the library median while reducing liver exposure by approximately 60%. Histopathology showed no treatment-related liver or lung toxicity. These findings define actionable formulation rules for tuning intraperitoneal mRNA-LNP delivery in PDAC and support further development of tumor-selective mRNA therapeutics for pancreatic cancer.

In vitro models are increasingly critical for interrogating cancer biology and therapeutic response, however, accurately recapitulating the tumor microenvironment (TME) remains a persistent challenge, particularly in head and neck cancers (HNC) characterized by complex cell-matrix interactions and heterogeneity. Current models often lack independent tunability of biochemical and biophysical cues, limiting systematic investigation of microenvironmental cues in a high-throughput format. Here, we establish a 3D droplet-based bioprinting platform for the fabrication of customizable in vitro TME models using poly(ethylene glycol) (PEG) hydrogels. Human HNC cell lines (FaDu and 2A3) with differing HPV statuses were bioprinted into PEG matrices spanning physiologically relevant stiffnesses (0.7-4.8 kPa) and compositions, including non-functionalized PEG and peptide-functionalized PEG (PEGfnc: RGD, YIGSR, CNYYSNS) and cultured for 7 days. Cluster growth, cell viability, and cluster morphology were assessed across multiple time points, matrix compositions, and matrix stiffnesses. Proliferation and endpoint phenotype expression were visualized using confocal microscopy through immunofluorescence. Results indicated enhanced cell viability in PEGfnc matrices, compared to non-functionalized matrices, while effect of matrix stiffness was less prominent. Median cluster size reached 40-50 m by day 7, and linear mixed-effects modeling identified how changes in cluster surface area, volume, and tumoroid complexity varied with cell type, matrix, and stiffness. By decoupling and systematically varying key TME parameters, this approach provides a robust and scalable framework for dissecting tumor-matrix interactions and advancing physiologically relevant in vitro models for cancer research and therapeutic screening.

Biomimetic tubular scaffolds hold great promise for tackling unmet clinical needs thanks to their biocompatibility and recapitulation of cellular microenvironments, conferring the ability to promote regeneration. Potential applications include small-diameter vascular implants and grafts for airway repair, for which no viable off-the-shelf solutions currently exist. The tubular materials (4 and 8 mm internal and external diameters) presented here consist purely of type I collagen, contain no chemical crosslinkers, and reproduce the multi-scale architecture of the native tissue including the presence of collagen fibrils. A novel two-step protocol provides materials with distinct concentric layers. A porous external structure, obtained by means of ice templating combined with collagen topotactic fibrillogenesis, favours oriented cell colonization. A smooth and much less porous internal layer provides mechanical and water-tightness properties relevant for in vivo implantation and promotes the formation of an endothelial monolayer under both static and flow conditions. The compliance of the double-layered materials under physiological pressure is close to that of piglet carotid arteries. The materials are also determined to be sufficiently flexible to provide the ability to perform ex vivo anastomosis with bronchi, although the relatively low value of suture retention strength remains a limitation for in vivo suturing.

The clinical translation of RNA interference (RNAi) therapeutics remains limited by inefficient delivery and cancer-target accumulation. Here, we report the development of a new cationic liposome (CLP) nanocarrier engineered for delivery and controlled-release of small interfering RNA (siRNA) targeting the epidermal growth factor receptor (EGFR) in human colorectal cancer. CLPs were synthesized from ethylphosphocholine-based lipids and PEGylated components, with folic acid (FA) tissue-specific ligand and fluorophore labelling. These nanocarriers exhibited robust physicochemical stability across a broad pH and temperature range, efficient siRNA complexation, and nuclease-protection of siRNA. Functional studies revealed that CLP-siEGFR achieved effective cytosolic siRNA cargo release and EGFR silencing in vitro, proving to be more effective than conventional lipid-based transfection systems. In human xenograft models, intravenously administered CLP-siEGFR showed enhanced tumor localization, prolonged siRNA retention, and significant tumor growth suppression, accompanied by marked downregulation of EGFR. Importantly, systemic dosing was well-tolerated, with no evidence of hepatotoxicity, nephrotoxicity, or hematological abnormalities. These results position CLP nanocarriers as an effective platform for targeted RNAi therapeutics, offering translational potential for precision oncology applications.

Nanoplastics generated from plastic waste in our ecosystems are becoming increasingly prevalent as bulk plastics exposed to natural factors like water and sunlight fragment to the nanoscale over time. These incidental nanoplastics span a wide range of physicochemical properties, which makes studying nanoplastic interactions in biological systems difficult. Here, we characterized the behavior of incidental nanoplastics generated through mechanical abrasion within coacervate droplets to probe the surface properties of the nanoplastics. We used elastin-like polypeptides (ELPs) to create hydrophobic or charged coacervate microenvironments. Using optical microscopy and fluorescence quantification, we observed that nanoplastics made from polyethylene terephthalate (nPET), nylon 6 (nPA), and polystyrene (nPS) exhibited distinct partitioning behavior with more favorable interactions with hydrophobic droplets. This indicated that the hydrophobic polymer backbone was the predominate surface feature despite exposed functional groups of the incidental nanoplastics, in contrast to findings with model carboxylated latex nanospheres (nPS-COOH). Furthermore, the selective partitioning of incidental nanoplastics into the hydrophobic droplets was able to capture over 80% of nPET in solution, and after recovery of the protein droplet, was able to cumulatively capture over 75% of the nPET feedstock across multiple cycles. This work explores the nuanced surface characteristics of incidental nanoplastics, expands the application of coacervates as chemical probes, and demonstrates a biopolymer approach for effective nanoplastic removal.

Medulloblastoma (MB) is an aggressive central nervous system (CNS) malignancy that primarily affects children and frequently exhibits metastasis to the leptomeninges of the brain and spinal cord. We developed a {beta}-Cyclodextrin-poly({beta}-Amino Ester) nanoparticle system to deliver the histone deactylase inhibitor (HDACi) Panobinostat to MB by the intrathecal route. Various imaging methods were utilized to study nanoparticle and payload fate following infusion into the cerebrospinal fluid (CSF) of mice via cisterna magna or lumbar access points. Nanoparticles dramatically improved penetration of hydrophobic small molecules into distal regions of the spinal cord. Panobinostat-loaded nanoparticles were effective at treating patient-derived MB, activating pharmacodynamic targets, slowing growth of the primary tumor, decreasing incidence of metastasis at the time of death, and ultimately prolonging survival. These studies provide insight into the mechanisms mediating transport of colloids and therapeutic molecules in the subarachnoid space and highlight new approaches for treating metastatic disease in the CNS.

Understanding how airborne particulates disrupt the alveolar barrier requires in vitro systems that recapitulate both the structure and transport properties of the lung air-blood interface. Here, we report a biodegradable lung alveoli-on-a-chip enabled by porous poly(lactic-co-glycolic acid)/polycaprolactone (PLGA/PCL) membranes with an interconnected porous architecture generated via porogen-assisted phase separation process. The membrane exhibits tunable degradation behavior, allowing progressive increases in surface porosity ([~]40%) and reduction in thickness ([~]3 {micro}m) during culture, while PCL maintains mechanical integrity under dynamic conditions. These degradation-driven structural changes regulate membrane transport properties, leading to enhanced permeability and supporting the formation of a functional epithelial-endothelial barrier under air-liquid interface (ALI) culture with breathing-mimetic cycling strain. Primary human alveolar epithelial and microvascular endothelial cells formed confluent, junctional monolayers on opposing membrane surfaces, exhibiting stable barrier function and high viability throughout the culture period. As a functional application, the platform was used to assess diesel particulate matter (DPM)-induced alveolar injury. Apical exposure to DPM induced dose-dependent cytotoxicity, increased barrier permeability, elevated reactive oxygen species, and DNA damage in both epithelial and endothelial layers, demonstrating trans-barrier propagation of particulate-induced injury. Pharmacological modulation with roflumilast-N-oxide (RNO), a phosphodiesterase-4 (PDE4) inhibitor, selectively attenuated oxidative stress and inflammatory responses, with limited effects on barrier integrity. Together, this work establishes degradable PLGA/PCL membranes as tunable interface materials for lung-on-a-chip systems, where structural evolution during degradation directly governs transport and barrier function. The resulting platform provides a physiologically relevant approach for studying particulate toxicity and therapeutic modulation at the alveolar interface.

The scalable fabrication of stable colloidosomes with controlled permeability and defined multicompartmental architecture remains a critical challenge, limiting their broader use in molecular delivery and environmental remediation. Here, we develop a hybrid lipid-metal-organic framework (lipid-MOF) colloidosome assembled through an interfacial emulsification strategy that integrates the structural rigidity of ZIF-8 particles with lipid-mediated membrane stabilization. During assembly, ZIF-8 particles accumulate at the oil-water interface to form a shell, producing hollow micron-sized spherical colloidosomes. The resulting colloidosomes exhibit excellent colloidal stability in aqueous media for over 30 days with a zeta potential of approximately -50 mV. Nitrogen adsorption measurements reveal a surface area of 45 m2g-1 and an average pore width of 4 nm. Fluorescence imaging shows that hydrophobic Nile red preferentially partitions into the colloidosomal membrane, whereas hydrophilic fluorescein isothiocyanate (FITC) localize predominantly within the aqueous interior, enabling simultaneous encapsulation of molecules with contrasting polarity with loading efficiencies approaching 90%. Furthermore, the colloidosomes demonstrate rapid removal of model pollutants from water, achieving >90% removal of methylene blue and metal ions without stirring. Together, these results introduce lipid-MOF colloidosomes as a new class of hybrid platforms that unify structural stability, multicompartmental encapsulation, and efficient adsorption behavior, opening pathways toward sustainable platforms for drug delivery and environmental bioremediation.

The endothelialization of organ-on-chip platforms and vascular implants is often limited by slow cell attachment and unstable monolayer formation. This work presents a scalable workflow that imprints micro- and nano-gratings into elastin-like recombinamer (ELR)-based hydrogels, enabling rapid endothelial cell capture and accelerating monolayer formation within 14 days. Three gelatin-ELR formulations are engineered, with {superscript 1}H-NMR confirming incorporation of sequences designed to modulate bioactivity (ELR1: inert; ELR2: uPA-responsive; ELR3: RGD-adhesive). ELR incorporation generates fibrillar microstructures and enhances mechanical performance, yielding elastic-dominant networks suitable for high-fidelity pattern transfer and stable culture. Using this library, the combined effects of ELR bioactivity and groove geometry on human iPSC-derived endothelial cells (iPSC-ECs) are systematically evaluated. In a 15-minute attachment assay, patterned ELR composites markedly improve cell retention compared to gelatin, with ELR2 on [~]350 nm and [~]4 {micro}m grooves performing best, consistent with controlled, cell-mediated interfacial remodeling. This early advantage persists, as ELR2 and ELR3 hydrogels support rapid alignment and reach confluence by day 14, whereas gelatin remains sub-confluent. Cytoskeletal analysis confirms F-actin alignment. By combining enhanced early capture with protease-regulated remodeling, ELR2 identifies a favorable design window. These results establish a materials design framework linking programmable ELR chemistry with surface topography to engineer endothelial interfaces, providing a versatile platform for vascular biomaterials and microphysiological systems.

The clinical translation of engineered skeletal muscle (eSM) for volumetric muscle regeneration is hindered by the challenge of establishing a functional vascular network capable of sustaining its high metabolic demand and ensuring graft survival. Here, we present a bottom-up biofabrication strategy to generate a pre-vascularized in vitro eSM model through the modular assembly of independently matured muscle and vascular compartments. C2C12 myoblasts were encapsulated within core-shell fibers using rotary wet-spinning (RoWS), yielding anisotropically aligned, multinucleated, and contractile myofibers expressing myosin heavy chain and sarcomeric -actinin. In parallel, gelatin methacryloyl (GelMA)-based microvascular seeds ({micro}VS), pre-endothelialized with human umbilical vein endothelial cells, were engineered to guide rapid and structurally stable vascular formation while preventing uncontrolled capillary self-organization. Fully endothelialized {micro}VS were incorporated into a pro-angiogenic bioink and processed via RoWS to generate tubular vascular fibers with physiological diameters (100-200 m) and continuous CD31-positive lumens. After independent maturation, muscle and vascular constructs were bioassembled into a hierarchically organized tissue and co-cultured. By decoupling myogenic and angiogenic differentiation, this strategy overcomes medium incompatibility typical of conventional co-cultures, preserving compartment-specific architecture and function and establishing a versatile platform for muscle-vascular modeling and translational muscle repair.

The human vasculature is a complex, multiscale system comprising hierarchical networks of macroscale to microscopic vessels. Existing in vitro fabrication techniques often fail to bridge these disparate scales, as high-resolution methods like multiphoton ablation are too slow for replicating larger vessels, while 3D printing lacks the resolution for fine microscale features. Here, we report a "twisted wire templating" strategy capable of generating perfusable bifurcating hydrogel networks that seamlessly transition from the macro- to the micro-scale (2.3 mm to 140 {micro}m) through seven orders of bifurcations. By optimizing wire-twisting geometries and polyurethane dip-coating, we overcame instability-driven bead formation to ensure replication fidelity across the networks. Fabrication rigs were reconfigured from existing 2D planar layouts to 3D reconfigurable architectures to better replicate 3D vessel geometries which simultaneously reducing the laboratory footprint and fabrication times by 47%. Using a Taguchi orthogonal array, we further optimized surface chemistry and hydrogel composition to inhibit structural failure during template extraction, resulting in fully patent, perfusable networks. This method provides a robust, low-cost, and scalable foundation for creating physiologically representative vascular models for investigating multiscale disease mechanisms and organ-level tissue engineering.

Microneedle (MN) patches have emerged as a highly efficient platform for localized drug delivery, showing great promise in cancer therapy due to their ability to enable precise drug administration. However, conventional MN systems are limited by the low drug-loading capacity of their tips and primarily rely on biologically inert, non-therapeutic matrices for structural support, which restricts further gains in antitumor efficacy. Herein, we present a strategy turning toxicity into therapy by constructing palladium nanoparticle-loaded polyvinyl alcohol/polyethyleneimine (PVA/PEI@Pd) hydrogel microneedles (PPPd-MNs), which exploit the intrinsic cytotoxicity of PEI for synergistic melanoma therapy. The PPPd-MNs efficiently catalyze the deprotection of a doxorubicin prodrug (P-DOX), enabling in situ generation of active doxorubicin (DOX). Notably, the PEI matrix serves a dual function: acting as a robust ligand to stabilize Pd catalysts and functioning as a therapeutic agent that disrupts cancer cell membranes. Both in vitro and in vivo experiments demonstrate that the combination of Pd-mediated bioorthogonal activation of DOX and PEI-induced membrane damage achieves a remarkable synergistic therapeutic outcome in a murine melanoma model, resulting in a tumor inhibition rate of up to 98%. This work repurposes the inherent cytotoxicity of the carrier material as an active therapeutic component, offering a novel paradigm for the design of high-performance bioorthogonal catalytic systems.

Curvature provides essential mechanical cues for epithelial cells, playing a key role in cell differentiation and morphology. Repeatable manufacture of precisely controlled curvature in soft hydrogel materials is therefore essential to study epithelial mechanobiology and function. Multiphoton (MP) based biofabrication holds promise due to its high resolution and three-dimensional design flexibility. Here, we leverage MPs advantages while increasing print speed to develop two complementary tools based on replica molding and multiphoton ablation. These can provide scalable hydrogel curvatures with tunable surface properties relevant for epithelial tissue engineering. In replica molding, MP prints are transferred into PDMS used to pattern centimeter scale arrays in hydrogels. In multiphoton ablation, hydrogels are locally degraded to generate precisely controlled curvatures and surface topography. With both methods, we repeatably guide epithelial cells into alveolar and duct-like shapes. Concave alveolar-like surfaces are shown to enhance the formation of thicker epithelial layers. We observe that surface properties, controlled by both tools, could enhance cytoskeletal organization. Using these biofabrication techniques, individual effects of curvature, surface properties, hydrogel composition, and bulk stiffness on epithelial cells can be studied. Both approaches offer high curvature control and throughput, providing a viable alternative to traditional 3D culture and other printing methods.

Bacterial Outer Membrane Vesicles (OMVs), spherical bilayered nanoparticles naturally released by all Gram-negative bacteria, are gaining increasing interest not only in the design of prophylactic vaccines but also in cancer immunotherapy. In particular, thanks to their potent built-in adjuvanticity and to their intrinsic capacity to directly kill tumor cells, OMVs have been successfully tested in intratumoral in situ vaccination (ISV), a strategy in which immunostimulatory formulations are injected directly into tumors to convert the tumor microenvironment (TME) into an immune-reactive state. Previous studies have shown that OMVs induce robust inflammation and a Th1-skewed immune response, resulting in complete tumor remission in a substantial fraction of mice bearing syngeneic tumors. Here, we show that OMVs from our Escherichia coli {Delta}60 strain can be efficiently engineered with multiple cytokines and chemokines. Moreover, CCL3, Flt3L, TNF, and IL-2 not only accumulated on the OMV surface but also retained their in vitro biological activity. Furthermore, OMVs displaying these cytokines exhibited potent antitumor activity, and in particular the intratumoral injection of the combined TNF- and IL-2-engineered OMVs eradicated tumors in over 95% of mice across several syngeneic models. Immunostaining and flow cytometry analyses revealed that injection of engineered OMVs markedly remodeled the TME, promoting the recruitment of inflammatory myeloid cells and {gamma}{delta} T cells, the persistence of local CD8 and CD4 {beta} T cells, and the reduction of regulatory T cells. Overall, these results highlight cytokine-bearing OMVs as a versatile and highly effective platform for intratumoral immunotherapy.

Engineering three-dimensional neuronal tissues with defined architecture and functional connectivity remains a critical challenge for applications in disease modeling, drug discovery, and regenerative medicine. Recently, a variety of fabrication methods have arisen, such as bioprinting or manual assembly of organoids, but often struggle with scalability, reproducibility, or maintaining cell viability. Here, two scaffold-free acoustic levitation bioreactors are introduced: one optimized for the culture of uniform neuronal spheroids, and another designed for the structuration of assembloids composed of distinct neuronal identities. Using acoustic standing waves, these platforms enable the contactless manipulation of cells and aggregates, facilitating the formation of highly viable functionally mature spheroids. This study shows that both striatal and cortical cell aggregates formed in acoustic levitation self-organize into spheroids within 24 hours and remain viable up to 10 days under these particular culture conditions without medium renewal. These neuro-spheroids demonstrate healthy development with increased growth and typical terminal differentiation and synaptic maturation. Moreover, concentric cortico-striatal assembloids were successfully structured and cultivated using optimized acoustofluidic chips. Offering versatile and scalable tools for engineering complex neuronal networks, acoustic levitation reveals itself as an innovative approach to 3D neuronal tissue modeling, with broad implications for bioengineering, regenerative medicine and fundamental neuroscience research.

Understanding how airborne particulates disrupt the human alveolar barrier requires in vitro systems that accurately replicate its composition and function. We present a biodegradable lung alveoli-on-a-chip that reproduces the architecture and physiology of the human air-blood interface using a porous poly(lactic-co-glycolic acid) (PLGA) membrane positioned between epithelium and endothelium under air-liquid interface (ALI) culture. The membrane, fabricated by porogen-assisted nonsolvent-induced phase separation, exhibited >50 % porosity, [~]2 {micro}m thickness, and mechanical compliance over 100-fold higher than conventional Transwell inserts, closely resembling the native interstitium. During co-culture, gradual PLGA degradation was compensated by cell-secreted extracellular-matrix (ECM) proteins such as collagen IV and laminin, forming a self-remodeling barrier that maintained integrity for at least 11 days. The platform supported stable epithelial-endothelial co-culture, high transepithelial electrical resistance, and physiologically relevant permeability. To demonstrate its utility, the chip was used to assess pulmonary toxicity of four types of waste-combustion-derived particulates, including rubber, plastic bags, plastic bottles, and textile fibers, delivered apically under ALI conditions. All combustion products reduced cell viability, increased hydrogen-peroxide release, and elevated {gamma}-H2AX expression, indicating oxidative and genotoxic stress, while disrupting barrier permeability. Rubber combustion particles elicited the most severe toxicity, causing the greatest loss of viability, accumulation of reactive oxygen species, and formation of DNA double-strand breaks. Together, these results establish a biodegradable, ECM-remodeling lung alveoli-on-a-chip as a physiologically relevant platform for investigating source-specific particulate toxicity and alveolar-barrier pathophysiology. By bridging environmental exposure models with human-relevant lung biology, this system provides a quantitative and translatable tool for evaluating respiratory risks and therapeutic interventions.

This article presents the development of an advanced modeling and simulation platform for carbon capture systems, with a focus on integrated process analysis from upstream CO2 capture through to bioethanol production. The platform supports the evaluation of CO2 mitigation technology by coupling mathematical bioprocess models with an interactive desktop application. The biological system employs Chlorella vulgaris microalgae to fix CO2 through photosynthesis and generate carbohydrate substrates, which are subsequently converted to bioethanol by Saccharomyces cerevisiae yeast via fermentation. The simulation integrates three established kinetic models--the Monod, Logistic, and Luedeking-Piret models--to predict biomass growth, substrate consumption, and ethanol yield under varying operational conditions. A closed-loop CO2 recycling subsystem captures fermentation off-gases and reintroduces them into the bioreactor, enhancing overall carbon utilization efficiency. Three representative simulation scenarios demonstrated process efficiencies ranging from 1.09% to 93.78% of the theoretical maximum CO2-to-ethanol conversion efficiency, confirming the platforms capacity to evaluate a wide operational envelope. The Electron/React-based desktop application provides real-time visualization, interactive 3D bioreactor models, and a simulation history module, making it accessible to researchers, engineers, and students. The platform serves as a digital twin that bridges rigorous bioprocess mathematics with intuitive user interaction, providing a cost-effective tool for designing and optimizing sustainable carbon capture and biofuel production systems.

Maintaining a confluent, antithrombotic endothelium on cardiovascular biomaterial surfaces remains a major barrier to long-term hemocompatibility, as endothelial cells (ECs) rapidly denude under supraphysiological shear in prosthetic devices. Here, we hypothesized that mesoscale surface geometry ([~]100-200 {micro}m) could reorganize near-wall hemodynamics, preserving endothelial coverage and function under extreme shear. Engineered microtrenches were introduced onto an implant biomaterial to generate spatially defined shear environments. Under supraphysiological near-wall shear ([~]250 dyn/cm{superscript 2}), microtrenched geometries created attenuated shear and vorticity gradients. Endothelial monolayers were sustained in these flow domains for 120 hours, whereas flat controls rapidly denuded. Endothelial retention in 22.5{degrees} angled trenches increased dramatically, from an EC of 33 to 101 dyn/cm{superscript 2}. 45{degrees} angled trenches further increased endothelial shear resistance to an EC of 207 dyn/cm{superscript 2}. Endothelial monolayers demonstrated collective mechano-adaptation to ultra-high shear through VE-cadherin junction thickening and coordinated cytoskeletal and nuclear alignment. Mechanoadapted monolayers exhibited increased eNOS expression correlated with local shear and elevated nitrite production (45{degrees}: 50.4 {+/-} 6.1 {micro}M; 22.5{degrees}: 35.7 {+/-} 3.3 {micro}M; 0{degrees}: 28.4 {+/-} 6.8 {micro}M). In contrast, interfaces with abrupt shear transitions or elevated rotational flow exhibited reduced coverage, junctional thinning, and re-emergence of VCAM-1 and PAI-1, indicating inflammatory and pro-thrombotic activation. Structural, functional, and inflammatory readouts exhibited peak responses within a shared shear-vorticity regime. Multivariate regression identified shear-vorticity coupling as the dominant predictor of endothelial persistence, with optima clustering within a mechanical range ({approx}0.8-2.9 x 10 dyn{middle dot}cm-{superscript 2}{middle dot}s-{superscript 1}). These findings establish geometry-driven modulation of near-wall flow as a predictive, material-agnostic strategy for endothelialization and vasoprotection of high-shear cardiovascular implants.