Expansion limits of meshed split-thickness skin grafts.

Split-thickness skin grafts are widely used to treat chronic wounds. Procedure design requires surgeons to predict how much a patch of the patient's own skin expands when it is meshed with rows of slits and stretched over a larger wound area. Accurate prediction of graft expansion remains a challenge, with current models overestimating the actual expansion, leading to suboptimal outcomes.

Energy barriers govern catheter herniation during endovascular procedures: a 2.5D vascular flow model analysis.

Endovascular procedures rely on navigating guidewires, catheters and other devices through tortuous vasculature to treat disease. A critical challenge in these procedures is catheter herniation, in which the device deviates from its intended path, often irrecoverably. To elucidate the mechanics of herniation, we developed a physical flow model of the aortic arch that enables direct measurement of device curvature during experimentally simulated neuroendovascular procedures conducted from an upper arterial access.

Estimates of natural frequencies for nuclear vibration, and an assessment of the feasibility of selective ultrasound ablation of cancer cells.

Selective ablation of cancer cells by ultrasound would be transformative for cancer therapy, but has not yet been possible. A key challenge is that cancerous and non-cancerous cells typically have similar acoustic impedance and are thus indistinguishable as materials in their responses to ultrasound. However, in certain cancers, cytoskeletal and nuclear lamin structures differ between healthy and malignant cells, opening the possibility of exploiting structural differences that manifest as different vibrational responses.

Tunable Viscoelasticity of Alginate Hydrogels via Serial Autoclaving.

Alginate hydrogels are widely used as biomaterials for cell culture and tissue engineering due to their biocompatibility and tunable mechanical properties. Reducing alginate molecular weight is an effective strategy for modulating hydrogel viscoelasticity and stress relaxation behavior, which can significantly impact cell spreading and fate. However, current methods like gamma irradiation to produce low molecular weight alginates suffer from high cost and limited accessibility.

Python tooth-inspired fixation device for enhanced rotator cuff repair.

Rotator cuff repair surgeries fail frequently, with 20 to 94% of the 600,000 repairs performed annually in the United States resulting in retearing of the rotator cuff. The most common cause of failure is sutures tearing through tendons at grasping points. To address this issue, we drew inspiration from the specialized teeth of snakes of the Pythonoidea superfamily, which grasp soft tissues without tearing.

The fibrous character of pericellular matrix mediates cell mechanotransduction.

Cells in solid tissues sense and respond to mechanical signals that are transmitted through extracellular matrix (ECM) over distances that are many times their size. This long-range force transmission is known to arise from strain-stiffening and buckling in the collagen fiber ECM network, but must also pass through the denser pericellular matrix (PCM) that cells form by secreting and compacting nearby collagen. However, the role of the PCM in the transmission of mechanical signals is still unclear.

In Vivo Porcine Model of Acute Iliocaval Deep Vein Thrombosis.

The study establishes a rapid, technically straightforward, and reproducible porcine large animal model for acute iliocaval deep vein thrombosis (DVT). The procedure can be performed with basic endovascular skillsets. With its procedural efficiency and consistency, the platform is promising for comparative in vivo testing of venous thrombectomy devices in a living host, and for future verification and validation studies to determine efficacy of novel thrombectomy devices relative to predicates.

Quantification of the flexural rigidity of endovascular surgical devices using three-point bending tests.

Endovascular surgical procedures require the navigation of catheters and wires through the vasculature to reach distal target sites. Quantitative frameworks for device selection hold the potential to improve the tracking of endovascular devices through vascular anatomy by personalizing the device flexural rigidity to an individual's anatomy. However, data are lacking to facilitate this technology, in part because typical endovascular devices have intricate spatial variations in mechanical properties that are challenging and tedious to quantify repeatably.

Plasmon-Enhanced Digital Fluoroimmunoassay for Subfemtomolar Detection of Protein Biomarkers.

Rapid and accurate quantification of low-abundance protein biomarkers in biofluids can transform the diagnosis of a range of pathologies, including infectious diseases. Here, we harness ultrabright plasmonic fluors as "digital nanolabels" and demonstrate the detection and quantification of subfemtomolar concentrations of human IL-6 and SARS-CoV-2 alpha and variant proteins in clinical nasopharyngeal swab and saliva samples from COVID-19 patients. The resulting digital plasmonic fluor-linked immunosorbent assay (digital p-FLISA) enables detection of SARS-CoV-2 nucleocapsid protein, both in solution and in live virions.

Genetically Engineered Protein-Based Bioadhesives with Programmable Material Properties.

Silk-amyloid-mussel foot protein (SAM) hydrogels made from recombinant fusion proteins containing β-amyloid peptide, spider silk domain, and mussel foot protein (Mfp) are attractive bioadhesives as they display a unique combination of tunability, biocompatibility, bioabsorbability, strong cohesion, and underwater adhesion to a wide range of biological surfaces. To design tunable SAM hydrogels for tailored surgical repair applications, an understanding of the relationships between protein sequence and hydrogel properties is imperative. Here, we fabricated SAM hydrogels using fusion proteins of varying lengths of silk-amyloid repeats and Mfps to characterize their structure and properties.

Dynamic control of contractile resistance to iPSC-derived micro-heart muscle arrays.

Many types of cardiovascular disease are linked to the mechanical forces placed on the heart. However, our understanding of how mechanical forces exactly affect the cellular biology of the heart remains incomplete. In vitro models based on cardiomyocytes derived from human induced pluripotent stem cells (iPSC-CM) enable researchers to develop medium to high-throughput systems to study cardiac mechanobiology at the cellular level.

Programmable and Reversible Integrin-Mediated Cell Adhesion Reveals Hysteresis in Actin Kinetics that Alters Subsequent Mechanotransduction.

Dynamically evolving adhesions between cells and extracellular matrix (ECM) transmit time-varying signals that control cytoskeletal dynamics and cell fate. Dynamic cell adhesion and ECM stiffness regulate cellular mechanosensing cooperatively, but it has not previously been possible to characterize their individual effects because of challenges with controlling these factors independently. Therefore, a DNA-driven molecular system is developed wherein the integrin-binding ligand RGD can be reversibly presented and removed to achieve cyclic cell attachment/detachment on substrates of defined stiffness.

Virtual blebbistatin: A robust and rapid software approach to motion artifact removal in optical mapping of cardiomyocytes.

Fluorescent reporters of cardiac electrophysiology provide valuable information on heart cell and tissue function. However, motion artifacts caused by cardiac muscle contraction interfere with accurate measurement of fluorescence signals. Although drugs such as blebbistatin can be applied to stop cardiac tissue from contracting by uncoupling calcium-contraction, their usage prevents the study of excitation-contraction coupling and, as we show, impacts cellular structure.

Stability of navigation in catheter-based endovascular procedures.

Endovascular procedures provide surgeons and other interventionalists with minimally invasive methods to treat vascular diseases by passing guidewires, catheters, sheaths and treatment devices into the vasculature to and navigate toward a treatment site. The efficiency of this navigation affects patient outcomes, but is frequently compromised by catheter "herniation", in which the catheter-guidewire system bulges out from the intended endovascular pathway so that the interventionalist can no longer advance it. Here, we showed herniation to be a bifurcation phenomenon that can be predicted and controlled using mechanical characterizations of catheter-guidewire systems and patientspecific clinical imaging.

Encoding and Storage of Information in Mechanical Metamaterials.

Information processing using material's own properties has gained increasing interest. Mechanical metamaterials, due to their diversity of deformation modes and wide design space, can be used to realize information processing, such as computing and storage. Here a mechanical metamaterial system is demonstrated for material-based encoding and storage of data through programmed reconfigurations of the metamaterial's structured building blocks.

Mechanobiology of cancer cell responsiveness to chemotherapy and immunotherapy: Mechanistic insights and biomaterial platforms.

Mechanical forces are central to how cancer treatments such as chemotherapeutics and immunotherapies interact with cells and tissues. At the simplest level, electrostatic forces underlie the binding events that are critical to therapeutic function. However, a growing body of literature points to mechanical factors that also affect whether a drug or an immune cell can reach a target, and to interactions between a cell and its environment affecting therapeutic efficacy.

Ultrasensitive lateral-flow assays via plasmonically active antibody-conjugated fluorescent nanoparticles.

Lateral-flow assays (LFAs) are rapid and inexpensive, yet they are nearly 1,000-fold less sensitive than laboratory-based tests. Here we show that plasmonically active antibody-conjugated fluorescent gold nanorods can make conventional LFAs ultrasensitive. With sample-to-answer times within 20 min, plasmonically enhanced LFAs read out via a standard benchtop fluorescence scanner attained about 30-fold improvements in dynamic range and in detection limits over 4-h-long gold-standard enzyme-linked immunosorbent assays, and achieved 95% clinical sensitivity and 100% specificity for antibodies in plasma and for antigens in nasopharyngeal swabs from individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Predicting YAP/TAZ nuclear translocation in response to ECM mechanosensing.

Cells translate mechanical cues from the extracellular matrix (ECM) into signaling that can affect the nucleus. One pathway by which such nuclear mechanotransduction occurs is a signaling axis that begins with integrin-ECM bonds and continues through a cascade of chemical reactions and structural changes that lead to nuclear translocation of YAP/TAZ. This signaling axis is self-reinforcing, with stiff ECM promoting integrin binding and thus facilitating polymerization and tension in the cytoskeletal contractile apparatus, which can compress nuclei, open nuclear pore channels, and enhance nuclear accumulation of YAP/TAZ.

An ECM-Mimicking, Injectable, Viscoelastic Hydrogel for Treatment of Brain Lesions.

Brain lesions can arise from traumatic brain injury, infection, and craniotomy. Although injectable hydrogels show promise for promoting healing of lesions and health of surrounding tissue, enabling cellular ingrowth and restoring neural tissue continue to be challenging. It is hypothesized that these challenges arise in part from the mismatch of composition, stiffness, and viscoelasticity between the hydrogel and the brain parenchyma, and this hypothesis is tested by developing and evaluating a self-healing hydrogel that not only mimics the composition, but also the stiffness and viscoelasticity of native brain parenchyma.

Programmable integrin and N-cadherin adhesive interactions modulate mechanosensing of mesenchymal stem cells by cofilin phosphorylation.

During mesenchymal development, the sources of mechanical forces transduced by cells transition over time from predominantly cell-cell interactions to predominantly cell-extracellular matrix (ECM) interactions. Transduction of the associated mechanical signals is critical for development, but how these signals converge to regulate human mesenchymal stem cells (hMSCs) mechanosensing is not fully understood, in part because time-evolving mechanical signals cannot readily be presented in vitro. Here, we established a DNA-driven cell culture platform that could be programmed to present the RGD peptide from fibronectin, mimicking cell-ECM interactions, and the HAVDI peptide from N-cadherin, mimicking cell-cell interactions, through DNA hybridization and toehold-mediated strand displacement reactions.

A Fenestrated Balloon Expandable Stent System for the Treatment of Aortoiliac Occlusive Disease.

In aortoiliac occlusive disease, atherosclerotic plaques can occlude the distal aortic bifurcation and proximal bilateral iliac artery and thus cause ischemia in the lower extremity. This is typically treated by restoring patency with balloon expandable stents. Stents are typically deployed in a "kissing stent" configuration into the bilateral iliac arteries and into the distal aortic bifurcation lumen to restore antegrade arterial flow.