Publications

2022
Koh E, Ambatipudi M, Boone DLL, Luehr JBW, Blaise A, Gonzalez J, Sule N, Mooney DJ, He EM. Quantifying face mask comfort. J Occup Environ Hyg. 2022;19 (1) :23-34.Abstract
Face mask usage is one of the most effective ways to limit SARS-CoV-2 transmission, but a mask is only useful if user compliance is high. Through anonymous surveys (n = 679), it was shown that mask discomfort is the primary source of noncompliance in mask wearing. Further, through these surveys, three critical predicting variables that dictate mask comfort were identified: air resistance, water vapor permeability, and face temperature change. To validate these predicting variables in a physiological context, experiments (n = 9) were performed to measure the respiratory rate and change in face temperature while wearing different types of three commonly used masks. Finally, using values of these predicting variables from experiments and the literature, and surveys asking users to rate the comfort of various masks, three machine learning algorithms were trained and tested to generate overall comfort scores for those masks. Although all three models performed with an accuracy of approximately 70%, the multiple linear regression model provides a simple analytical expression to predict the comfort scores for common face masks provided the input predicting variables. As face mask usage is crucial during the COVID-19 pandemic, the goal of this quantitative framework to predict mask comfort is hoped to improve user experience and prevent discomfort-induced noncompliance.
Özkale B, Lou J, Özelçi E, Elosegui-Artola A, Tringides CM, Mao AS, Sakar MS, Mooney DJ. Actuated 3D microgels for single cell mechanobiology. Lab Chip. 2022.Abstract
We present a new cell culture technology for large-scale mechanobiology studies capable of generating and applying optically controlled uniform compression on single cells in 3D. Mesenchymal stem cells (MSCs) are individually encapsulated inside an optically triggered nanoactuator-alginate hybrid biomaterial using microfluidics, and the encapsulating network isotropically compresses the cell upon activation by light. The favorable biomolecular properties of alginate allow cell culture in vitro up to a week. The mechanically active microgels are capable of generating up to 15% compressive strain and forces reaching 400 nN. As a proof of concept, we demonstrate the use of the mechanically active cell culture system in mechanobiology by subjecting singly encapsulated MSCs to optically generated isotropic compression and monitoring changes in intracellular calcium intensity.
Freedman BR, Knecht RS, Tinguely Y, Eskibozkurt EG, Wang CS, Mooney DJ. Aging and matrix viscoelasticity affect multiscale tendon properties and tendon derived cell behavior. Acta Biomater. 2022;143 :63-71.Abstract
Aging is the largest risk factor for Achilles tendon associated disorders and rupture. Although Achilles tendon macroscale elastic properties are suggested to decline with aging, less is known about the effect of maturity and aging on multiscale viscoelastic properties and their effect on tendon cell behavior. Here, we show dose dependent changes in native multiscale tendon mechanical and structural properties and uncover several nanoindentation properties predicted by tensile mechanics and echogenicity. Alginate hydrogel systems designed to mimic juvenile tendon microscale mechanics revealed that stiffness and viscoelasticity affected Achilles tendon cell aspect ratio and proliferation during aging. This knowledge provides further evidence for the negative impact of maturity and aging on tendon and begins to elucidate how viscoelasticity can control tendon derived cell morphology and expansion. STATEMENT OF SIGNIFICANCE: Aging is the largest risk factor for Achilles tendon associated disorders and rupture. Although Achilles tendon macroscale elastic properties are suggested to decline with aging, less is known about the effect of maturity and aging on multiscale viscoelastic properties and their effect on tendon cell behavior. Here, we show dose dependent changes in native multiscale tendon mechanical and structural properties and uncover several nanoindentation properties predicted by tensile mechanics and echogenicity. Alginate hydrogel systems designed to mimic juvenile tendon microscale mechanics revealed that stiffness and viscoelasticity affected Achilles tendon cell spreading and proliferation during aging. This knowledge provides further evidence for the negative impact of maturity and aging on tendon and begins to elucidate how viscoelasticity can control tendon derived cell morphology and expansion.
Tatara AM, Gandhi RG, Mooney DJ, Nelson SB. Antiplatelet therapy for Staphylococcus aureus bacteremia: Will it stick?. PLoS Pathog. 2022;18 (2) :e1010240.Abstract
Staphylococcus aureus bacteremia (SAB) remains a clinically challenging infection despite extensive investigation. Repurposing medications approved for other indications is appealing as clinical safety profiles have already been established. Ticagrelor, a reversible adenosine diphosphate receptor antagonist that prevents platelet aggregation, is indicated for patients suffering from acute coronary syndrome (ACS). However, some clinical data suggest that patients treated with ticagrelor are less likely to have poor outcomes due to S. aureus infection. There are several potential mechanisms by which ticagrelor may affect S. aureus virulence. These include direct antibacterial activity, up-regulation of the innate immune system through boosting platelet-mediated S. aureus killing, and prevention of S. aureus adhesion to host tissues. In this Pearl, we review the clinical data surrounding ticagrelor and infection as well as explore the evidence surrounding these proposed mechanisms of action. While more evidence is needed before antiplatelet medications formally become part of the arsenal against S. aureus infection, these potential mechanisms represent exciting pathways to target in the host/pathogen interface.
Najibi AJ, Shih T-Y, Mooney DJ. Cryogel vaccines effectively induce immune responses independent of proximity to the draining lymph nodes. Biomaterials. 2022;281 :121329.Abstract
The delivery location of traditional vaccines can impact immune responses and resulting efficacy. Cryogel-based cancer vaccines, which are typically injected near the inguinal lymph nodes (iLNs), recruit and activate dendritic cells (DC) in situ, induce DC homing to the iLNs, and have generated potent anti-tumor immunity against several murine cancer models. However, whether cryogel vaccination distance to a draining LN affects the kinetics of DC homing and downstream antigen-specific immunity is unknown, given the heightened importance of the scaffold vaccine site. We hypothesized that vaccination near the iLNs would lead to more rapid DC trafficking to the iLNs, thereby inducing faster and stronger immune responses. Here, mice were injected with cryogel vaccines against ovalbumin either adjacent or distal to the iLNs, and the resultant DC trafficking kinetics, T cell phenotypes, antigen-specific T cell and humoral responses, and prophylactic efficacy in an ovalbumin-expressing tumor model were assessed. Cryogel vaccines induced potent, long-lasting antigen-specific immune responses independent of distance to the iLNs, with no significant differences in DC trafficking kinetics, ovalbumin-specific T cell and antibody responses, or prophylactic efficacy. Moreover, DC trafficking and activation state were not impacted when cryogels were injected near a tumor. These results demonstrate a flexibility in vaccination location for scaffold-based vaccines, independent of draining LN distance.
Matoori S, Mooney DJ. Development of a liposomal near-infrared fluorescence lactate assay for human blood. Biomaterials. 2022;283 :121475.Abstract
In emergency medicine, blood lactate is a commonly used biomarker of hypoxia (e.g., sepsis, trauma, cardiac arrest) but the median time to obtain the results from a clinical lactate test is 3 h. We recently developed a near-infrared fluorescent blood lactate assay based on a two-step enzymatic cascade in a vesicular reaction compartment. Previously, we reported a response of this assay to lactate-spiked bovine blood after 10 min. To develop a point-of-care test, we optimized this assay in commercial human blood, validated it in fresh capillary blood of healthy volunteers in an institutional review board-approved study, and improved the stability of the formulation. External pH and luminal enzyme concentrations were identified as key parameters of sensor response and kinetics, as they impact transmembrane lactate diffusion and turnover rate. The preparation process was also simplified and the stability was improved to allow storage at 4 °C for at least 5 days. The final formulation exhibited a strong and linear response to lactate-spiked human blood in a clinically relevant range, and accurately quantified a lactate standard at a clinically used cut-off in fresh capillary blood after 2 min. These findings motivate a clinical evaluation of this rapid and easy-to-use lactate assay.
Freedman BR, Kuttler A, Beckmann N, Nam S, Kent D, Schuleit M, Ramazani F, Accart N, Rock A, Li J, et al. Enhanced tendon healing by a tough hydrogel with an adhesive side and high drug-loading capacity. Nat Biomed Eng. 2022.Abstract
Hydrogels that provide mechanical support and sustainably release therapeutics have been used to treat tendon injuries. However, most hydrogels are insufficiently tough, release drugs in bursts, and require cell infiltration or suturing to integrate with surrounding tissue. Here we report that a hydrogel serving as a high-capacity drug depot and combining a dissipative tough matrix on one side and a chitosan adhesive surface on the other side supports tendon gliding and strong adhesion (larger than 1,000 J m-2) to tendon on opposite surfaces of the hydrogel, as we show with porcine and human tendon preparations during cyclic-friction loadings. The hydrogel is biocompatible, strongly adheres to patellar, supraspinatus and Achilles tendons of live rats, boosted healing and reduced scar formation in a rat model of Achilles-tendon rupture, and sustainably released the corticosteroid triamcinolone acetonide in a rat model of patellar tendon injury, reducing inflammation, modulating chemokine secretion, recruiting tendon stem and progenitor cells, and promoting macrophage polarization to the M2 phenotype. Hydrogels with 'Janus' surfaces and sustained-drug-release functionality could be designed for a range of biomedical applications.
Habibi N, Brown TD, Adu-Berchie K, Christau S, Raymond JE, Mooney DJ, Mitragotri S, Lahann J. Nanoparticle Properties Influence Transendothelial Migration of Monocytes. Langmuir. 2022.Abstract
Nanoparticle-based delivery of therapeutics to the brain has had limited clinical impact due to challenges crossing the blood-brain barrier (BBB). Certain cells, such as monocytes, possess the ability to migrate across the BBB, making them attractive candidates for cell-based brain delivery strategies. In this work, we explore nanoparticle design parameters that impact both monocyte association and monocyte-mediated BBB transport. We use electrohydrodynamic jetting to prepare nanoparticles of varying sizes, compositions, and elasticity to address their impact on uptake by THP-1 monocytes and permeation across the BBB. An in vitro human BBB model is developed using human cerebral microvascular endothelial cells (hCMEC/D3) for the assessment of migration. We compare monocyte uptake of both polymeric and synthetic protein nanoparticles (SPNPs) of various sizes, as well as their effect on cell migration. SPNPs (human serum albumin/HSA or human transferrin/TF) are shown to promote increased monocyte-mediated transport across the BBB over polymeric nanoparticles. TF SPNPs (200 nm) associate readily, with an average uptake of 138 particles/cell. Nanoparticle loading is shown to influence the migration of THP-1 monocytes. The migration of monocytes loaded with 200 nm TF and 200 nm HSA SPNPs was 2.3-fold and 2.1-fold higher than that of an untreated control. RNA-seq analysis after TF SPNP treatment suggests that the upregulation of several migration genes may be implicated in increased monocyte migration (ex. integrin subunits α M and α L). Integrin β 2 chain combines with either integrin subunit α M chain or integrin subunit α L chain to form macrophage antigen 1 and lymphocyte function-associated antigen 1 integrins. Both products play a pivotal role in the transendothelial migration cascade. Our findings highlight the potential of SPNPs as drug and/or gene delivery platforms for monocyte-mediated BBB transport, especially where conventional polymer nanoparticles are ineffective or otherwise not desirable.
Seo BR, Mooney DJ. Recent and Future Strategies of Mechanotherapy for Tissue Regenerative Rehabilitation. ACS Biomater Sci Eng. 2022.Abstract
Mechanotherapy, the application of various mechanical forces on injured or diseased tissue, is a viable option for tissue regenerative rehabilitation. Recent advances in tissue engineering (i.e., engineered materials and 3D printing) and soft-robotic technologies have enabled systematic and controlled studies to demonstrate the therapeutic impacts of mechanical stimulation on severely injured tissue. Along with innovation in actuation systems, improvements in analysis methods uncovering cellular and molecular landscapes during tissue regeneration under mechanical loading expand our understanding of how mechanical cues are translated into specific biological responses (i.e., stem cell self-renewal and differentiation, immune responses, etc.). Moving forward, the development of diversified actuation systems that are mechanically tissue friendly, easily scalable, and capable of delivering various modes of loading and monitoring functional biomarkers will facilitate systematic and controlled preclinical and clinical studies. Combining these future actuation systems with single-cell resolution analysis of cellular and molecular markers will enable detailed knowledge of underlying biological responses, and optimization of mechanotherapy protocols for specific tissues/injuries. These advancements will enable diverse mechanotherapy therapies in the future.
Wu DT, Jeffreys N, Diba M, Mooney DJ. Viscoelastic Biomaterials for Tissue Regeneration. Tissue Eng Part C Methods. 2022.Abstract
The extracellular matrix (ECM) mechanical properties regulate key cellular processes in tissue development and regeneration. The majority of scientific investigation has focused on ECM elasticity as the primary mechanical regulator of cell and tissue behavior. However, all living tissues are viscoelastic, exhibiting both solid- and liquid-like mechanical behavior. Despite increasing evidence regarding the role of ECM viscoelasticity in directing cellular behavior, this aspect is still largely overlooked in the design of biomaterials for tissue regeneration. Recently, with the emergence of various bottom-up material design strategies, new approaches can deliver unprecedented control over biomaterial properties at multiple length scales, thus enabling the design of viscoelastic biomaterials that mimic various aspect of the native tissue ECM microenvironment. This review describes key considerations for the design of viscoelastic biomaterials for tissue regeneration. We provide an overview of the role of matrix viscoelasticity in directing cell behavior towards regenerative outcomes, highlight recent strategies utilizing viscoelastic hydrogels for regenerative therapies, and outline remaining challenges, potential solutions, and emerging applications for viscoelastic biomaterials in tissue engineering and regenerative medicine.
Super M, Doherty EJ, Cartwright MJ, Seiler BT, Langellotto F, Dimitrakakis N, White DA, Stafford AG, Karkada M, Graveline AR, et al. Biomaterial vaccines capturing pathogen-associated molecular patterns protect against bacterial infections and septic shock. Nat Biomed Eng. 2022;6 (1) :8-18.Abstract
Most bacterial vaccines work for a subset of bacterial strains or require the modification of the antigen or isolation of the pathogen before vaccine development. Here we report injectable biomaterial vaccines that trigger potent humoral and T-cell responses to bacterial antigens by recruiting, reprogramming and releasing dendritic cells. The vaccines are assembled from regulatorily approved products and consist of a scaffold with absorbed granulocyte-macrophage colony-stimulating factor and CpG-rich oligonucleotides incorporating superparamagnetic microbeads coated with the broad-spectrum opsonin Fc-mannose-binding lectin for the magnetic capture of pathogen-associated molecular patterns from inactivated bacterial-cell-wall lysates. The vaccines protect mice against skin infection with methicillin-resistant Staphylococcus aureus, mice and pigs against septic shock from a lethal Escherichia coli challenge and, when loaded with pathogen-associated molecular patterns isolated from infected animals, uninfected animals against a challenge with different E. coli serotypes. The strong immunogenicity and low incidence of adverse events, a modular manufacturing process, and the use of components compatible with current good manufacturing practice could make this vaccine technology suitable for responding to bacterial pandemics and biothreats.
2021
Shah NJ, Mao AS, Shih T-Y, Kerr MD, Sharda A, Raimondo TM, Weaver JC, Vrbanac VD, Deruaz M, Tager AM, et al. Author Correction: An injectable bone marrow-like scaffold enhances T cell immunity after hematopoietic stem cell transplantation. Nat Biotechnol. 2021;39 (11) :1466.
Tringides CM, Mooney DJ. Materials for Implantable Surface Electrode Arrays: Current Status and Future Directions. Adv Mater. 2021 :e2107207.Abstract
Surface electrode arrays are mainly fabricated from rigid or elastic materials, and precisely manipulated ductile metal films, which offer limited stretchability. However, the living tissues to which they are applied are nonlinear viscoelastic materials, which can undergo significant mechanical deformation in dynamic biological environments. Further, the same arrays and compositions are often repurposed for vastly different tissues rather than optimizing the materials and mechanical properties of the implant for the target application. By first characterizing the desired biological environment, and then designing a technology for a particular organ, surface electrode arrays may be more conformable, and offer better interfaces to tissues while causing less damage. Here, the various materials used in each component of a surface electrode array are first reviewed, and then electrically active implants in three specific biological systems, the nervous system, the muscular system, and skin, are described. Finally, the fabrication of next-generation surface arrays that overcome current limitations is discussed.
Shih T-Y, Najibi AJ, Bartlett AL, Li AW, Mooney DJ. Ultrasound-triggered release reveals optimal timing of CpG-ODN delivery from a cryogel cancer vaccine. Biomaterials. 2021;279 :121240.Abstract
Recently, several injectable scaffold-based cancer vaccines have been developed that can recruit and activate host dendritic cells (DCs) and generate potent antitumor responses. However, the optimal timing of adjuvant delivery, particularly of the commonly used cytosine-phosphodiester-guanine-oligonucleotide (CpG-ODN), for scaffold-based cancer vaccines remains unknown. We hypothesized that optimally timed CpG-ODN delivery will lead to enhanced immune responses, and designed a cryogel vaccine system where CpG-ODN release can be triggered on-demand by ultrasound. CpG-ODN was first condensed with polyethylenimine and then adsorbed to cryogels. Little adsorbed CpG-ODN was released in vitro. Ultrasound stimulation triggered continuous CpG-ODN release, at an enhanced rate even after ultrasound was turned off, with minimal burst release. In vivo, ultrasound stimulation four days post-vaccination induced a significantly higher antigen-specific cytotoxic T-lymphocyte (CTL) response compared to control mice. Furthermore, ultrasound stimulation at this time point generated a significantly higher IgG2a/c antibody titer than all the groups except ultrasound stimulation eight days post-vaccination. This optimal timing of ultrasound-triggered release coincided with peak DC accumulation in the cryogels. By enabling temporal control of vaccine components through release on-demand, this system is a promising platform to study the optimal timing of delivery of immunomodulatory agents for cancer vaccination.
Raimondo TM, Mooney DJ. Anti-inflammatory nanoparticles significantly improve muscle function in a murine model of advanced muscular dystrophy. Sci Adv. 2021;7 (26).Abstract
Chronic inflammation contributes to the pathogenesis of all muscular dystrophies. Inflammatory T cells damage muscle, while regulatory T cells (Tregs) promote regeneration. We hypothesized that providing anti-inflammatory cytokines in dystrophic muscle would promote proregenerative immune phenotypes and improve function. Primary T cells from dystrophic (mdx) mice responded appropriately to inflammatory or suppressive cytokines. Subsequently, interleukin-4 (IL-4)- or IL-10-conjugated gold nanoparticles (PA4, PA10) were injected into chronically injured, aged, mdx muscle. PA4 and PA10 increased T cell recruitment, with PA4 doubling CD4+/CD8- T cells versus controls. Further, 50% of CD4+/CD8- T cells were immunosuppressive Tregs following PA4, versus 20% in controls. Concomitant with Treg recruitment, muscles exhibited increased fiber area and fourfold increases in contraction force and velocity versus controls. The ability of PA4 to shift immune responses, and improve dystrophic muscle function, suggests that immunomodulatory treatment may benefit many genetically diverse muscular dystrophies, all of which share inflammatory pathology.
Li Y, Mao AS, Seo BR, Zhao X, Gupta SK, Chen M, Han Y, Shih T-Y, Mooney DJ, Guo M. Generation of the Compression-induced Dedifferentiated Adipocytes (CiDAs) Using Hypertonic Medium. Bio Protoc. 2021;11 (4) :e3920.Abstract
Current methods to obtain mesenchymal stem cells (MSCs) involve sampling, culturing, and expanding of primary MSCs from adipose, bone marrow, and umbilical cord tissues. However, the drawbacks are the limited numbers of total cells in MSC pools, and their decaying stemness during in vitro expansion. As an alternative resource, recent ceiling culture methods allow the generation of dedifferentiated fat cells (DFATs) from mature adipocytes. Nevertheless, this process of spontaneous dedifferentiation of mature adipocytes is laborious and time-consuming. This paper describes a modified protocol for in vitro dedifferentiation of adipocytes by employing an additional physical stimulation, which takes advantage of augmenting the stemness-related Wnt/β-catenin signaling. Specifically, this protocol utilizes a polyethylene glycol (PEG)-containing hypertonic medium to introduce extracellular physical stimulation to obtain higher efficiency and introduce a simpler procedure for adipocyte dedifferentiation.
Langellotto F, Dellacherie MO, Yeager C, Ijaz H, Yu J, Cheng C-A, Dimitrakakis N, Seiler BT, Gebre MS, Gilboa T, et al. A Modular Biomaterial Scaffold-Based Vaccine Elicits Durable Adaptive Immunity to Subunit SARS-CoV-2 Antigens. Adv Healthc Mater. 2021;10 (22) :e2101370.Abstract
The coronavirus disease 2019 (COVID-19) pandemic demonstrates the importance of generating safe and efficacious vaccines that can be rapidly deployed against emerging pathogens. Subunit vaccines are considered among the safest, but proteins used in these typically lack strong immunogenicity, leading to poor immune responses. Here, a biomaterial COVID-19 vaccine based on a mesoporous silica rods (MSRs) platform is described. MSRs loaded with granulocyte-macrophage colony-stimulating factor (GM-CSF), the toll-like receptor 4 (TLR-4) agonist monophosphoryl lipid A (MPLA), and SARS-CoV-2 viral protein antigens slowly release their cargo and form subcutaneous scaffolds that locally recruit and activate antigen-presenting cells (APCs) for the generation of adaptive immunity. MSR-based vaccines generate robust and durable cellular and humoral responses against SARS-CoV-2 antigens, including the poorly immunogenic receptor binding domain (RBD) of the spike (S) protein. Persistent antibodies over the course of 8 months are found in all vaccine configurations tested and robust in vitro viral neutralization is observed both in a prime-boost and a single-dose regimen. These vaccines can be fully formulated ahead of time or stored lyophilized and reconstituted with an antigen mixture moments before injection, which can facilitate its rapid deployment against emerging SARS-CoV-2 variants or new pathogens. Together, the data show a promising COVID-19 vaccine candidate and a generally adaptable vaccine platform against infectious pathogens.
Ambatipudi M, Carrillo Gonzalez P, Tasnim K, Daigle JT, Kulyk T, Jeffreys N, Sule N, Trevino R, He EM, Mooney DJ, et al. Risk quantification for SARS-CoV-2 infection through airborne transmission in university settings. J Occup Environ Hyg. 2021;18 (12) :590-603.Abstract
The COVID-19 pandemic has significantly impacted learning as many institutions switched to remote or hybrid instruction. An in-depth assessment of the risk of infection that considers environmental setting and mitigation strategies is needed to make safe and informed decisions regarding reopening university spaces. A quantitative model of infection probability that accounts for space-specific parameters is presented to enable assessment of the risk in reopening university spaces at given densities. The model uses the fraction of the campus population that are viral shedders, room capacity, face covering filtration efficiency, air exchange rate, room volume, and time spent in the space as parameters to calculate infection probabilities in teaching spaces, dining halls, dorms, and shared bathrooms. The model readily calculates infection probabilities in various university spaces, with face covering filtration efficiency and air exchange rate being among the dominant variables. When applied to university spaces, this model demonstrated that, under specific conditions that are feasible to implement, in-person classes could be held in large lecture halls with an infection risk over the semester <1%. Meal pick-ups from dining halls and usage of shared bathrooms in residential dormitories among small groups of students could also be accomplished with low risk. The results of applying this model to spaces at Harvard University (Cambridge and Allston campuses) and Stanford University are reported. Finally, a user-friendly web application was developed using this model to calculate infection probability following input of space-specific variables. The successful development of a quantitative model and its implementation through a web application may facilitate accurate assessments of infection risk in university spaces. However, since this model is thus far unvalidated, validation using infection rate and contact tracing data from university campuses will be crucial as such data becomes available at larger scales. In light of the impact of the COVID-19 pandemic on universities, this tool could provide crucial insight to students, faculty, and university officials in making informed decisions.
Seo BR, Payne CJ, McNamara SL, Freedman BR, Kwee BJ, Nam S, de Lázaro I, Darnell M, Alvarez JT, Dellacherie MO, et al. Skeletal muscle regeneration with robotic actuation-mediated clearance of neutrophils. Sci Transl Med. 2021;13 (614) :eabe8868.Abstract
Mechanical stimulation (mechanotherapy) can promote skeletal muscle repair, but a lack of reproducible protocols and mechanistic understanding of the relation between mechanical cues and tissue regeneration limit progress in this field. To address these gaps, we developed a robotic device equipped with real-time force control and compatible with ultrasound imaging for tissue strain analysis. We investigated the hypothesis that specific mechanical loading improves tissue repair by modulating inflammatory responses that regulate skeletal muscle regeneration. We report that cyclic compressive loading within a specific range of forces substantially improves functional recovery of severely injured muscle in mice. This improvement is attributable in part to rapid clearance of neutrophil populations and neutrophil-mediated factors, which otherwise may impede myogenesis. Insights from this work will help advance therapeutic strategies for tissue regeneration broadly.
Tringides CM, Vachicouras N, de Lázaro I, Wang H, Trouillet A, Seo BR, Elosegui-Artola A, Fallegger F, Shin Y, Casiraghi C, et al. Viscoelastic surface electrode arrays to interface with viscoelastic tissues. Nat Nanotechnol. 2021;16 (9) :1019-1029.Abstract
Living tissues are non-linearly elastic materials that exhibit viscoelasticity and plasticity. Man-made, implantable bioelectronic arrays mainly rely on rigid or elastic encapsulation materials and stiff films of ductile metals that can be manipulated with microscopic precision to offer reliable electrical properties. In this study, we have engineered a surface microelectrode array that replaces the traditional encapsulation and conductive components with viscoelastic materials. Our array overcomes previous limitations in matching the stiffness and relaxation behaviour of soft biological tissues by using hydrogels as the outer layers. We have introduced a hydrogel-based conductor made from an ionically conductive alginate matrix enhanced with carbon nanomaterials, which provide electrical percolation even at low loading fractions. Our combination of conducting and insulating viscoelastic materials, with top-down manufacturing, allows for the fabrication of electrode arrays compatible with standard electrophysiology platforms. Our arrays intimately conform to the convoluted surface of the heart or brain cortex and offer promising bioengineering applications for recording and stimulation.

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