Biology subjects

Cosgriff-Hernandez, E.

Publications and source records attributed to Cosgriff-Hernandez, E..

14 recordsLinked to original sources

bioRxiv2026

Off-the-Shelf Multilayer Vascular Grafts with Damage-Resistant Hydrogel Coatings Incorporating Integrin Targeting

Synthetic grafts remain ineffective for small-caliber vascular applications due to thrombosis and intimal hyperplasia. To address these limitations, our lab designed a multilayer graft consisting of a hydrogel coating that promotes post-implantation endothelialization and an electrospun mesh that matches arterial mechanical properties. Damage-resistant hydrogels were engineered using a double-network system composed of polyether urethane diacrylamide and N-acryloyl glycinamide to enhance fracture resistance through hydrogen bonding. In this study, we utilized redox initiation to apply conformal, durable hydrogels to electrospun grafts. Bioactivity wa introduced using streptococcal collagen-like proteins containing 1{beta}1 and 2{beta}1 integrin-binding motifs, enabling selective cell-material interactions that support endothelialization while preserving acute thromboresistance. To establish the feasibility of these grafts as off-the-shelf devices, we evaluated coating integrity and bioactivity retention following sterilization and dynamic physiological loading. Sterilized composites exhibited surgically-associated damage resistance, indicating that sterilization did not compromise hydrogel durability. Coating integrity and bioactivity were also preserved after six weeks of physiological loading. Acut thromboresistance was supported by both static platelet adhesion assays and dynamic whole-blood bioreactor studies using heparinized blood, with low platelet adhesion observed relative to ePTFE. Finally, a pilot ovine carotid model demonstrated successful surgical handling and sustained graft patency. Collectively, these results highlight the promise of multilayer vascular grafts as durable, thromboresistant conduits for small-diameter vascular applications. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=60 SRC="FIGDIR/small/741222v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@14ec910org.highwire.dtl.DTLVardef@17259e8org.highwire.dtl.DTLVardef@6cb611org.highwire.dtl.DTLVardef@1251d7d_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2026

Mechanical History and Substrate Stiffness Shape Integrin-Mediated Endothelial Cell Behavior on Bioactive Hydrogels

Synthetic blood contacting devices frequently fail due to the lack of requisite biochemical and biomechanical cues needed to support transanastamotic endothelialization. During transanastomotic endothelialization, endothelial cells experience dynamic changes in extracellular mechanical cues as they migrate from compliant native vessels onto stiffer blood contacting device surfaces. However, how substrate stiffness and mechanical memory from prior mechanical environments influence temporal integrin remodeling and downstream endothelialization processes necessary to establish a stable endothelial layer remains poorly understood. In this study, human coronary artery endothelial cells (HCECs) were cultured on substrates spanning physiologically relevant stiffnesses to determine how substrate mechanics regulate collagen binding integrins and endothelialization. Increasing substrate stiffness promoted time dependent upregulation of 2{beta}1 integrin expression, whereas 1{beta}1 expression remained unchanged. Enhanced 2{beta}1 expression on stiff substrates was accompanied by increased vinculin associated focal adhesion maturation and accelerated endothelialization, characterized by increased proliferation, migration, and progression to confluence prior to reaching quiescence after 1 week. To better model transanastomotic migration and investigate mechanical history effects, cells initially expanded on compliant hydrogels were transferred to stiff substrates. Although these cells exhibited transient reductions in 2{beta}1 expression at early timepoints compared with tissue culture polystyrene expanded controls, no persistent differences in focal adhesion maturation, proliferation, migration, confluence, or quiescence were observed. Collectively, these findings demonstrate that substrate stiffness is a primary regulator of the early endothelialization processes required to establish a stable endothelial monolayer, whereas the influence of mechanical history is transient and ultimately superseded by the current mechanical environment. These findings also identify 2{beta}1 mediated mechanotransduction as a potential design target for blood contacting biomaterials that promote rapid endothelialization while supporting long-term endothelial cell quiescence.

bioengineering↗

bioRxiv2026

Design of a Conductive Hydrogel Coating to Improve Catheter-Tissue Coupling in Radiofrequency Ablation

Radiofrequency ablation is a mainstay of cardiac rhythm management despite high recurrence rates. Current radiofrequency ablation catheters are limited by poor contact with trabeculated cardiac tissue that promotes uneven heating with hot spots that cause collateral damage and regions of incomplete ablation that promote recurrence. Herein, we report on a conductive hydrogel coating of radiofrequency ablation catheters to improve tissue contact while promoting efficient energy transfer. A method was developed to graft a polyether urethane diacrylamide hydrogel to the distal tip of the catheter that maintained stable adhesion following drying, sterilization, and rehydration. The coating also remained intact after passage through an introducer sheath and 50 cycles of radiofrequency ablation at clinical power. The hydrogel-coated catheter demonstrated enhanced tissue contact that was dependent on hydrogel modulus. Hydrogel-mediated ablation prevented steam pop incidence and generated homogeneous lesions in an ex vivo ablation model; however, increased hydrogel conductivity is needed to achieve comparable lesion dimensions as the bare metal catheter and prevent coating damage at higher power. Collectively, these results establish a tunable hydrogel coating method that addresses limitations of conventional radiofrequency ablation and offers a promising approach to enhance the safety and efficacy of cardiac ablation therapies.

bioengineering↗

bioRxiv2026

3D Microscale Mechanical Simulations of Hydrogel Coated Electrospun Meshes

Electrospun fiber meshes have long served as biomaterials in a wide range of biomedical applications due to their functional similarities to extracellular matrix and highly tunable properties. Altering the mechanical behaviors of individual fibers and their microarchitecture (e.g.; diameter, crimp, orientation, density) can in principle be used to control bulk level behaviors. Moreover, electrospun meshes are often combined with softer coatings and hydrogels to control surface interactions with body tissues. Yet, fully optimizing their behaviors for specific applications remains an elusive target due to a continued lack of understanding of the micromechanical mechanisms and their relation to bulk mechanical behaviors. Our goal herein was to understand how actual nanoCT-generated 3D microfiber geometry can be used to predict bulk mechanical properties of hydrogel-mesh composites. Electrospun polyurethane meshes were fabricated with a random fiber orientation and coated with a PEG-based hydrogel. The fiber-hydrogel composite was then imaged with a nanoCT scanner at a voxel resolution of 180 nm. From these images, custom Python programs were written to segment, refine, and tesselate a high-resolution finite element of the fiber mesh and hydrogel volumes into a single integrated bi-material finite element model. The resulting mesh was used to run simulations of the planar biaxial mechanical tests used to characterize the bulk mechanical behaviors. Our framework thus enabled systematic investigations of both the macroscopic bulk mechanical response of the overall fiber mesh and the microscopic localized mechanical response of fibers under various stages of loading. The resultant simulations were accurate and predictive of the bulk mechanical responses. It is interesting to note that the fiber-hydrogel composite material experienced the largest stresses within the fiber phase and the largest strains within the hydrogel. This key result underscores that while the previous analytical model assumed local affine deformations, at the microscale this assumption does not hold. We also found very different effective fiber stress-strain responses in each model. It is likely these differences are due to the substantial heterogeneous non-affine local deformations present in the actual fiber-hydrogel composite. This finding further reveals the need for more rigorous approaches to better understand how electrospun-based materials function in order to improve their use in modern medical devices and implants.

bioengineering↗

bioRxiv2025

Characterization of Sex-Based Differences in Integrin-Mediated Endothelial Cel Adhesion to Bioactive Hydrogels

Endothelialization promotes thromboresistance in blood-contacting devices, but biomaterial designs often overlook sex differences in endothelialization processes. In this study, we elucidated sex differences in endothelial cell-material interactions through investigation of the integrin-ligand interplay with biomaterial substrates and the corollary effects on cell adhesion and spreading. First, integrin expression of human coronary artery endothelial cells (HCAECs) was characterized for age-matched donors (3 male, 3 female). Sex-based differences in integrin expression were identified, with notably higher 2{beta}1, 5{beta}1, and V{beta}3 expression in female cells and higher 1{beta}1 expression in male cells. On polyethylene glycol (PEG)-based hydrogel incorporating collagen or gelatin, female cells showed increased attachment on stiff substrates as compared to male HCAECs, likely driven by increased 2{beta}1, 5{beta}1, and V{beta}3 expression in female cells. Collectively, these results demonstrate sex-biased endothelial cell responses to bioactive hydrogels mediated by integrin interactions and highlight the importance of incorporating biological sex as a design variable in the development of blood-contacting biomaterials. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=72 SRC="FIGDIR/small/656802v2_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@41bfb9org.highwire.dtl.DTLVardef@921619org.highwire.dtl.DTLVardef@e8df4corg.highwire.dtl.DTLVardef@9c0faa_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

Co-Electrospinning Extracellular Matrix with Polycaprolactone Enables a Modular Approach to Balance Bioactivity and Mechanics of a Multifunctional Bone Wrap

Decellularized tissue possesses significant regenerative potential, yet fabricating complex extracellular matrix (ECM) scaffolds remains challenging. Blending with synthetic polymers can aid ECM fabrication but often relies on digested ECM and encapsulation within the synthetic matrix can limit cell-ECM interactions. We recently developed a suspension electrospinning platform to facilitate ECM scaffold fabrication without the need for digestion or polymer-carriers. Its integration into a co- electrospinning system enables modular design of composite scaffolds to combine the regenerative potential of ECM with the advantages of synthetic polymers. This study directly compares co- electrospinning and blend electrospinning of polycaprolactone and small intestinal submucosa (SIS) for use as a bone wrap to augment membrane durability, sustain infection control, and enhance vascularity in Masquelets induced membrane technique. Co-spun wraps demonstrated improved handling properties as compared to ECM wraps and solvent welding was used to achieve target suture retention standards without diminishing SIS content. Unlike the blended wraps, the co-spun wraps supported full-thickness cell infiltration within 4 weeks, released gentamicin at a bactericidal concentration for 6 weeks, and demonstrated enhanced angiogenic properties. Collectively, these findings highlight the functionality of a co-electrospinning modular design and demonstrate the efficacy of using a co-spun wrap in bone tissue engineering applications.

bioengineering↗

bioRxiv2025

Advanced Manufacturing of Coil-Reinforced Multilayer Vascular Grafts to Optimize Biomechanical Performance

Small diameter vascular grafts require a complex balance of biomechanical properties to achieve target burst pressure, arterial compliance-matching, and kink resistance to prevent failure. Iterative design of our multilayer vascular was previously used to achieve high compliance while retaining the requisite burst pressure and suture retention strength for clinical use. To impart kink resistance, a custom 3D solution printer was used to add a polymeric coil to the electrospun polyurethane graft to support the graft during bending. The addition of this reinforcing coil increased kink resistance but reduced compliance. A matrix of grafts were fabricated and tested to establish key structure-property relationships between coil parameters (spacing, diameter, modulus) and biomechanical properties (compliance, kink radius). A successful graft design was identified with a compliance similar to saphenous vein grafts (4.1 {+/-} 0.4 %/mmHgx10-2) while maintaining comparable kink resistance to grafts used currently in the clinic. To explore graft combinations that could increase graft compliance to match arterial values while retaining this kink resistance, we utilized finite element (FE) models of compliance and kink radius that simulated experimental testing. The FE-predicted graft compliance agreed well with experimental values. Although the kink model over-predicted the experimental kink radius values, key trends between graft parameters and kink resistance were reproduced. As an initial proof-of-concept, the validated models were then utilized to parse through a targeted graft design space. Although this initial parameter range tested did not yield a graft that improved upon the previous balance of graft properties, this combination of advanced manufacturing and computational framework paves the way for future model-driven design to further optimize graft performance. TOC O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=97 SRC="FIGDIR/small/633374v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@faca56org.highwire.dtl.DTLVardef@f9dccforg.highwire.dtl.DTLVardef@fbb5corg.highwire.dtl.DTLVardef@d5c021_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2024

Design of PEG-based hydrogels as soft ionic conductors

Conductive hydrogels have gained interest in biomedical applications and soft electronics. To tackle the challenge of ionic hydrogels falling short of desired mechanical properties in previous studies, our investigation aimed to understand the pivotal structural factors that impact the conductivity and mechanical behavior of polyethylene glycol (PEG)-based hydrogels with ionic conductivity. Polyether urethane diacrylamide (PEUDAm), a functionalized long-chain macromer based on PEG, was used to synthesize hydrogels with ionic conductivity conferred by incorporating ions into the liquid phase of hydrogel. The impact of salt concentration, water content, temperature, and gel formation on both mechanical properties and conductivity was characterized to establish parameters for tuning hydrogel properties. To further expand the range of conductivity available in these ionic hydrogels, 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) was incorporated as a single copolymer network or double network configuration. As expected, conductivity in these ionic gels was primarily driven by ion diffusivity and charge density, which was dependent on hydrogel network formation and swelling. Copolymer network structure had minimal effect on the conductivity which was primarily driven by counter-ion equilibrium; however, the mechanical properties and equilibrium swelling was strongly dependent on network structure. The structure-property relationships elucidated here enables the rationale design of this new double network hydrogel to achieve target properties for a broad range of applications.

bioengineering↗

bioRxiv2024

Suspension Electrospinning of Decellularized Extracellular Matrix

Decellularized extracellular matrices (dECM) have strong regenerative potential as tissue engineering scaffolds; however, current clinical options for dECM are limited to freeze-drying its native form into sheets. Electrospinning is a versatile scaffold fabrication technique that allows control of macro- and microarchitecture. It remains challenging to electrospin dECM; which has led researchers to either blend it with synthetic materials or use enzymatic digestion to fully solubilize the dECM. Both strategies reduce the innate bioactivity of dECM and limit its regenerative potential. Herein, we developed a new suspension electrospinning method to fabricate a pure dECM scaffold that retains its innate bioactivity. Systematic investigation of suspension parameters was used to identify critical rheological properties required to instill "spinnability," including homogenization, concentration, and particle size. Homogenization enhanced particle interaction to impart the requisite elastic behavior to withstand electrostatic drawing without breaking. A direct correlation between concentration and viscosity was observed that altered fiber morphology; whereas, particle size had minimal impact on suspension properties and fiber morphology. The versatility of this new method was demonstrated by electrospinning dECM with three common decellularization techniques (Abraham, Badylak, Luo) and tissue origins (intestinal submucosa, heart, skin). Bioactivity retention after electrospinning was confirmed using cell proliferation, angiogenesis, and macrophage assays. Collectively, these findings provide a framework for researchers to electrospin dECM for diverse tissue engineering applications. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=78 SRC="FIGDIR/small/577473v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@f6ff3org.highwire.dtl.DTLVardef@17efb2dorg.highwire.dtl.DTLVardef@19c5b9dorg.highwire.dtl.DTLVardef@42a13e_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2024

Polycaprolactone-based shape memory foams as self-fitting vaginal stents

There is an urgent critical need for a patient-forward vaginal stent that can prevent debilitating vaginal stenosis that occurs in up to 75% of patients who undergo pelvic radiation treatments and adolescent patients after vaginal reconstruction. To this end, we developed a self-fitting vaginal stent based on a shape-memory polymer (SMP) foam that can assume a secondary, compressed shape for ease of deployment. Upon insertion, the change in temperature and hydration initiates foam expansion to shape fit to the individual patient and restore the lumen of the stent to allow egress of vaginal secretions. To achieve rapid actuation at physiological temperature, we investigated the effect of architecture of two photocurable, polycaprolactone (PCL) macromers. Star-PCL-tetraacrylate displayed reduced melting temperature in the target range as compared to the linear-PCL-diacrylate. Emulsion-templating was then used to fabricate foams from 75:25 water-in-oil (W/O) emulsions that were subsequently annealed to yield high-porosity SMP foams. Upon axial shape memory testing, both foams displayed excellent shape fixity (90%); however, only the PCL star-foams displayed shape recovery ([~]84%) at 37{degrees}C to its permanent shape. A custom mold and curing system was then used to fabricate PCL star- foams into hollow, cylindrical stents. The stent was crimped to its temporary insertion shape (50% reduction in diameter, OD [~] 11 mm) with a custom radial crimper and displayed excellent shape fixity for deployment (> 95%) and shape recovery ([~] 100%). To screen vaginal stents, we developed a custom benchtop pelvic model that simulated vaginal anatomy, temperatures, and pressures with an associated computational model. A hysteroscope was used to visualize stent expansion and deformation via a scope port near the cervix of the benchtop model. A crimped SMP vaginal stent was deployed in the model and expanded to walls of the canal ([~]70% increase in cross-sectional area) in less than 5 minutes after irrigation with warm water. The vaginal stent demonstrated retention of vaginal caliber with less than 1% decrease in cross-sectional area under physiological pressure. Collectively, this work demonstrates the potential for SMP foams as self-fitting vaginal stents to prevent stenosis. Additionally, this work provides new open-source tools for the iterative design of other gynecological devices. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=87 SRC="FIGDIR/small/577474v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@1bc3162org.highwire.dtl.DTLVardef@4e5657org.highwire.dtl.DTLVardef@1069d33org.highwire.dtl.DTLVardef@13aa9da_HPS_FORMAT_FIGEXP M_FIG C_FIG Created in BioRender

bioengineering↗

bioRxiv2023

Eliminating steam pops and improving lesion safety in atrial ablation with conductive hydrogels

BackgroundAtrial fibrillation (AF) is a significant burden worldwide, and the existing treatments leave much to be desired. There are, however, opportunities to improve the safety and efficacy of the most popular treatment, radiofrequency (RF) cardiac ablation, using conductive hydrogels as an ablation mediator. MethodsLesions were created in ex vivo ventricular tissues using bare metal traditional RF catheters and three different hydrogels with varying conductivities to assess the effect of conductivity on lesion formation. Similar procedures were performed in atrial/esophageal tissue stacks to mimic physiological AF ablation and demonstrate the initial safety profile of conductive hydrogel-mediated ablation. ResultsThe hydrogel mediated lesions were overall shallower and narrower than bare metal, and also exhibited less char and improved lesion homogeneity. The hydrogel also eliminated steam pops. Finally, the hydrogel appeared to be more thermally protective of the esophagus in the atrial/esophageal tissue stack, greatly reducing the lesion formation on the esophagus while still achieving transmural lesions in the atrial tissue. ConclusionsHydrogel-mediated RF ablation holds promise as a novel method to improve ablation outcomes for AF patients. Future work will confirm this in vivo and establish the chemistry required to create a conductive hydrogel coating for RF ablation catheters.

bioengineering↗

bioRxiv2023

Hydrogel-Polyurethane Fiber Composites With Enhanced Microarchitectural Control For Heart Valve Replacement

Polymeric heart valves offer the potential to overcome the limited durability of tissue based bioprosthetic valves and the need for anticoagulant therapy of mechanical valve replacement options. However, developing a single-phase material with requisite biological properties and target mechanical properties remains a challenge. In this study, a composite heart valve material was developed where an electrospun mesh provides tunable mechanical properties and a hydrogel coating confers an antifouling surface for thromboresistance. Key biological responses were evaluated in comparison to glutaraldehyde-fixed pericardium. Platelet and bacterial attachment were reduced by 38% and 98%, respectively, as compared to pericardium that demonstrated the antifouling nature of the hydrogel coating. There was also a notable reduction (59%) in the calcification of the composite material as compared to pericardium. A custom 3D printed hydrogel coating setup was developed to make valve composites for device-level hemodynamic testing. Regurgitation fraction (9.6 {+/-} 1.8%) and effective orifice area (1.52 {+/-} 0.34 cm2) met ISO 5840-2:2021 requirements. Additionally, the mean pressure gradient was comparable to current clinical bioprosthetic heart valves demonstrating preliminary efficacy. Although the hemodynamic properties are promising, it is anticipated that the random microarchitecture will result in suboptimal strain fields and peak stresses that may accelerate leaflet fatigue and degeneration. Previous computational work has demonstrated that bioinspired fiber microarchitectures can improve strain homogeneity of valve materials toward improving durability. To this end, we developed advanced electrospinning methodologies to achieve polyurethane fiber microarchitectures that mimic or exceed the physiological ranges of alignment, tortuosity, and curvilinearity present in the native valve. Control of fiber alignment from a random fiber orientation at a normalized orientation index (NOI) 14.2 {+/-} 6.9% to highly aligned fibers at a NOI of 85.1 {+/-} 1.4%. was achieved through increasing mandrel rotational velocity. Fiber tortuosity and curvilinearity in the range of native valve features were introduced through a post-spinning annealing process and fiber collection on a conical mandrel geometry, respectively. Overall, these studies demonstrate the potential of hydrogel-polyurethane fiber composite as a heart valve material. Future studies will utilize the developed advanced electrospinning methodologies in combination with model-directed fabrication toward optimizing durability as a function of fiber microarchitecture.

bioengineering↗

bioRxiv2023

Bacterial mechanosensing of surface stiffness promotes signaling and growth leading to biofilm formation by Pseudomonas aeruginosa

The attachment of bacteria onto a surface, consequent signaling, and the accumulation and growth of the surface-bound bacterial population are key initial steps in the formation of pathogenic biofilms. While recent reports have hinted that the stiffness of a surface may affect the accumulation of bacteria on that surface, the processes that underlie bacterial perception of and response to surface stiffness are unknown. Furthermore, whether, and how, the surface stiffness impacts biofilm development, after initial accumulation, is not known. We use thin and thick hydrogels to create stiff and soft composite materials, respectively, with the same surface chemistry. Using quantitative microscopy, we find that the accumulation, motility, and growth of the opportunistic human pathogen Pseudomonas aeruginosa respond to surface stiffness, and that these are linked through cyclic-di-GMP signaling that depends on surface stiffness. The mechanical cue stemming from surface stiffness is elucidated using finite-element modeling combined with experiments - adhesion to stiffer surfaces results in greater changes in mechanical stress and strain in the bacterial envelope than does adhesion to softer surfaces with identical surface chemistry. The cell-surface-exposed protein PilY1 acts as a mechanosensor, that upon surface engagement, results in higher cyclic-di-GMP levels, lower motility, and greater accumulation on stiffer surfaces. PilY1 impacts the biofilm lag phase, which is extended for bacteria attaching to stiffer surfaces. This study shows clear evidence that bacteria actively respond to different stiffness of surfaces where they adhere via perceiving varied mechanical stress and strain upon surface engagement. ImportanceBacteria colonize many types of biological and medical surfaces with a large range of stiffnesses. Colonization leads to the formation of biofilms, which cause costly and life-impairing chronic infections. However, whether and how bacteria can sense and respond to the mechanical cue provided by surface stiffness has remained unknown. We find that bacteria do indeed respond to surface stiffness in a way that is both consistent with expectations based on equilibrium continuum mechanics and that quantitatively impacts multiple aspects of early biofilm formation. This is a new understanding for the nascent field of bacterial mechanobiology. Furthermore, this finding suggests the possibility of a new category of approaches to hindering biofilm development by tuning the mechanical properties of biomedical surfaces.

microbiology↗

bioRxiv2021

Towards prevention of re-entrant arrhythmias: Injectable hydrogel electrodes enable direct capture of previously inaccessible cardiac tissues

Re-entrant arrhythmias--the leading cause of sudden cardiac death--are caused by diseased myocardial tissue and consequent delayed myocardial conduction. Access to the coronary veins that cross the "culprit" scar regions where re-entry originates can provide improved pacing to these delayed regions, offering a novel opportunity to prevent ventricular arrhythmias and circumvent the need for painful defibrillation, risky cardiac ablation, or toxic and often ineffective antiarrhythmic medications. However, there are no pacing electrodes which are small or focal enough to navigate these tributaries. To address this need, we have developed an injectable conductive hydrogel that can fill the epicardial coronary veins and their mid-myocardial tributaries. When connected to a standard pacing lead, these injected hydrogels can be converted into flexible electrodes that directly pace the previously inaccessible mid-myocardial tissue. In our two-component system, hydrogel precursor solutions can be injected through a dual lumen catheter in a minimally invasive deployment strategy to provide direct access to the diseased regions with precision and ease. Mixing of the two solutions upon injection into the vein activates redox-initiated crosslinking of the gel for rapid in situ cure without an external stimulus. An ex vivo porcine model was used to identify the requisite viscosity and cure rate for gel retention and homogeneity. Ionic species added to the hydrogel precursor solutions conferred conductivity above target myocardium values that was retained after implantation. Successful in vivo deployment demonstrated that the hydrogel electrode filled the anterior interventricular vein with extension into the septal (mid-myocardial) venous tributaries to depths far more distal and refined than any current technologies allow. In addition to successful capture and pacing of the heart, analysis of surface ECG tracings revealed a novel pacing observation highly specific for and suggestive of capture of extensive swaths of septal myocardial tissue. This is the first report of an injectable electrode used to successfully pace the mid-myocardium and mimic physiologic conduction. Furthermore, in vivo cardiac electroanatomical mapping studies in an ablation scar model showed uniform capture along the hydrogel in the vessels as well as increased capture area compared to point pacing. Collectively, these findings demonstrate that this injectable hydrogel electrode can be deployed to scarred regions of the heart to provide a reliable pacing modality that most closely resembles native conduction with the potential to eliminate delayed myocardial conduction and associated re-entry. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=179 SRC="FIGDIR/small/467102v2_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@1577526org.highwire.dtl.DTLVardef@cc510dorg.highwire.dtl.DTLVardef@1dd426eorg.highwire.dtl.DTLVardef@1346aab_HPS_FORMAT_FIGEXP M_FIG C_FIG One Sentence SummaryInjectable hydrogel electrodes achieve pacing that mimics physiologic conduction by capturing midmyocardial tissue

bioengineering↗