A Printed Microscopic Universal Gradient Interface for Super Stretchable Strain-Insensitive Bioelectronics.

Stretchable electronics capable of conforming to nonplanar and dynamic human body surfaces are central for creating implantable and on-skin devices for high-fidelity monitoring of diverse physiological signals. While various strategies have been developed to produce stretchable devices, the signals collected from such devices are often highly sensitive to local strain, resulting in inevitable convolution with surface strain-induced motion artifacts that are difficult to distinguish from intrinsic physiological signals. Here all-printed super stretchable strain-insensitive bioelectronics using a unique universal gradient interface (UGI) are reported to bridge the gap between soft biomaterials and stiff electronic materials.

Modular Assembly of Metamaterials Using Light Gradients.

This is a report on a pilot study that tests the feasibility of assembling photonic metamaterials (PMs) using light gradient forces. Following a strategy that works like modular construction, light gradient forces, produced by a tightly focused, 1D standing wave optical trap, time-multiplexed across a 2D lattice are used to assemble voxels consisting of prefabricated, monodispersed nanoparticles (NPs) with radii ranging from 30 to 500 nm into 3D structures on a hydrogel scaffold. Hundreds of NPs can be manipulated concurrently into a complex heterogeneous voxel this way, and then the process can be repeated by stitching together voxels to form a metamaterial of any size, shape, and constituency although imperfectly.

Leveraging 3D Bioprinting and Photon-Counting Computed Tomography to Enable Noninvasive Quantitative Tracking of Multifunctional Tissue Engineered Constructs.

3D bioprinting is revolutionizing the fields of personalized and precision medicine by enabling the manufacturing of bioartificial implants that recapitulate the structural and functional characteristics of native tissues. However, the lack of quantitative and noninvasive techniques to longitudinally track the function of implants has hampered clinical applications of bioprinted scaffolds. In this study, multimaterial 3D bioprinting, engineered nanoparticles (NPs), and spectral photon-counting computed tomography (PCCT) technologies are integrated for the aim of developing a new precision medicine approach to custom-engineer scaffolds with traceability.

Biocompatible, Multi-Mode, Fluorescent, MRI Contrast Magnetoelectric-Silica Nanoparticles (MagSiNs), for On-Demand Doxorubicin Delivery to Metastatic Cancer Cells.

There is a need to improve current cancer treatment regimens to reduce systemic toxicity, to positively impact the quality-of-life post-treatment. We hypothesized the negation of off-target toxicity of anthracyclines (e.g.

Methacrylate-Modified Gold Nanoparticles Enable Non-Invasive Monitoring of Photocrosslinked Hydrogel Scaffolds.

Photocrosslinked hydrogels, such as methacrylate-modified gelatin (gelMA) and hyaluronic acid (HAMA), are widely utilized as tissue engineering scaffolds and/or drug delivery vehicles, but lack a suitable means for non-invasive, longitudinal monitoring of surgical placement, biodegradation, and drug release. Therefore, we developed a novel photopolymerizable X-ray contrast agent, methacrylate-modified gold nanoparticles (AuMA NPs), to enable covalent-linking to methacrylate-modified hydrogels (gelMA and HAMA) in one-step during photocrosslinking and non-invasive monitoring by X-ray micro-computed tomography (micro-CT). Hydrogels exhibited a linear increase in X-ray attenuation with increased Au NP concentration to enable quantitative imaging by contrast-enhanced micro-CT.

Tissue engineered drug delivery vehicles: Methods to monitor and regulate the release behavior.

Tissue engineering is a rapidly evolving, multidisciplinary field that aims at generating or regenerating 3D functional tissues for in vitro disease modeling and drug screening applications or for in vivo therapies. A variety of advanced biological and engineering methods are increasingly being used to further enhance and customize the functionality of tissue engineered scaffolds. To this end, tunable drug delivery and release mechanisms are incorporated into tissue engineering modalities to promote different therapeutic processes, thus, addressing challenges faced in the clinical applications.

Nanomaterials for bioprinting: functionalization of tissue-specific bioinks.

Three-dimensional (3D) bioprinting is rapidly evolving, offering great potential for manufacturing functional tissue analogs for use in diverse biomedical applications, including regenerative medicine, drug delivery, and disease modeling. Biomaterials used as bioinks in printing processes must meet strict physiochemical and biomechanical requirements to ensure adequate printing fidelity, while closely mimicking the characteristics of the native tissue. To achieve this goal, nanomaterials are increasingly being investigated as a robust tool to functionalize bioink materials.

Colloidal stability, cytotoxicity, and cellular uptake of HfO nanoparticles.

The colloidal stability, cytotoxicity, and cellular uptake of hafnium oxide (HfO ) nanoparticles (NPs) were investigated in vitro to assess safety and efficacy for use as a deliverable theranostic in nanomedicine. Monoclinic HfO NPs, ~60-90 nm in diameter and ellipsoidal in shape, were directly prepared without calcination by a hydrothermal synthesis at 83% yield. The as-prepared, bare HfO NPs exhibited colloidal stability in cell culture media for at least 10 days without significant agglomeration or settling.

Effects of porogen morphology on the architecture, permeability, and mechanical properties of hydroxyapatite whisker reinforced polyetheretherketone scaffolds.

Porous polyetheretherketone (PEEK) and bioactive hydroxyapatite (HA) reinforced PEEK scaffolds have attracted recent interest for enabling biologic fixation of orthopaedic and spinal implants, such as interbody spinal fusion cages. Porous PEEK and HA-PEEK scaffolds have been prepared by compression molding and leaching a fugitive porogen, most commonly NaCl salt crystals which exhibit a cubic morphology. Ellipsoidal or spherical porogen particles have been suggested to improve pore interconnectivity and permeability in scaffolds through improved porogen particle contact compared with a cubic porogen, but a direct comparison without concomitant effects from other factors is lacking.

Phage-mimicking antibacterial core-shell nanoparticles.

The increasing frequency of nosocomial infections caused by antibiotic-resistant microorganisms concurrent with the stagnant discovery of new classes of antibiotics has made the development of new antibacterial agents a critical priority. Our approach is an antibiotic-free strategy drawing inspiration from bacteriophages to combat antibiotic-resistant bacteria. We developed a nanoparticle-based antibacterial system that structurally mimics the protein-turret distribution on the head structure of certain bacteriophages and explored a combination of different materials arranged hierarchically to inhibit bacterial growth and ultimately kill pathogenic bacteria.

Mineral deposition and vascular invasion of hydroxyapatite reinforced collagen scaffolds seeded with human adipose-derived stem cells.

Background: Collagen-based scaffolds reinforced with hydroxyapatite (HA) are an attractive choice for bone tissue engineering because their composition mimics that of bone. We previously reported the development of compression-molded collagen-HA scaffolds that exhibited high porosity, interconnected pores, and mechanical properties that were well-suited for surgical handling and fixation. The objective of this study was to investigate these novel collagen-HA scaffolds in combination with human adipose-derived stem cells (hASCs) as a template for bone formation in a subcutaneous athymic mouse model.

Quantification of multiple mixed contrast and tissue compositions using photon-counting spectral computed tomography.

Quantitative material decomposition of multiple mixed, or spatially coincident, contrast agent (gadolinium and iodine) and tissue (calcium and water) compositions is demonstrated using photon-counting spectral computed tomography (CT). Material decomposition is performed using constrained maximum likelihood estimation (MLE) in the image domain. MLE is calibrated by multiple linear regression of all pure material compositions, which exhibits a strong correlation ( ) between the measured x-ray attenuation in each photon energy bin and known concentrations in the calibration phantom.

Nondestructive, longitudinal measurement of collagen scaffold degradation using computed tomography and gold nanoparticles.

Biodegradable materials, such as collagen scaffolds, are used extensively in clinical medicine for tissue regeneration and/or as an implantable drug delivery vehicle. However, available methods to study biomaterial degradation are typically invasive, destructive, and/or non-volumetric. Therefore, the objective of this study was to investigate a new method for nondestructive, longitudinal, and volumetric measurement of collagen scaffold degradation.

Exfoliated Graphene Leads to Exceptional Mechanical Properties of Polymer Composite Films.

Polymers with superior mechanical properties are desirable in many applications. In this work, polyethylene (PE) films reinforced with exfoliated thermally reduced graphene oxide (TrGO) fabricated using a roll-to-roll hot-drawing process are shown to have outstanding mechanical properties. The specific ultimate tensile strength and Young's modulus of PE/TrGO films increased monotonically with the drawing ratio and TrGO filler fraction, reaching up to 3.

Effects of bisphosphonate ligands and PEGylation on targeted delivery of gold nanoparticles for contrast-enhanced radiographic detection of breast microcalcifications.

A preclinical murine model of hydroxyapatite (HA) breast microcalcifications (µcals), which are an important clinical biomarker for breast cancer detection, was used to investigate the independent effects of high affinity bisphosphonate (BP) ligands and a polyethylene glycol (PEG) spacer on targeted delivery of gold nanoparticles (Au NPs) for contrast-enhanced radiographic detection. The addition of BP ligands to PEGylated Au NPs (BP-PEG-Au NPs) resulted in five-fold greater binding affinity for targeting HA µcals, as expected, due to the strong binding affinity of BP ligands for calcium. Therefore, BP-PEG-Au NPs were able to target HA µcals in vivo after intramammary delivery, which enabled contrast-enhanced radiographic detection of µcals in both normal and radiographically dense mammary tissues similar to previous results for BP-Au NPs, while PEG-Au NPs did not.

Super-resolution fluorescence microscopy by stepwise optical saturation.

Super-resolution fluorescence microscopy is an important tool in biomedical research for its ability to discern features smaller than the diffraction limit. However, due to its difficult implementation and high cost, the super-resolution microscopy is not feasible in many applications. In this paper, we propose and demonstrate a saturation-based super-resolution fluorescence microscopy technique that can be easily implemented and requires neither additional hardware nor complex post-processing.

The fracture toughness of small animal cortical bone measured using arc-shaped tension specimens: Effects of bisphosphonate and deproteinization treatments.

Small animal models, and especially transgenic models, have become widespread in the study of bone mechanobiology and metabolic bone disease, but test methods for measuring fracture toughness on multiple replicates or at multiple locations within a single small animal bone are lacking. Therefore, the objective of this study was to develop a method to measure cortical bone fracture toughness in multiple specimens and locations along the diaphysis of small animal bones. Arc-shaped tension specimens were prepared from the mid-diaphysis of rabbit ulnae and loaded to failure to measure the radial fracture toughness in multiple replicates per bone.

Effects of calibration methods on quantitative material decomposition in photon-counting spectral computed tomography using a maximum a posteriori estimator.

Purpose: Advances in photon-counting detectors have enabled quantitative material decomposition using multi-energy or spectral computed tomography (CT). Supervised methods for material decomposition utilize an estimated attenuation for each material of interest at each photon energy level, which must be calibrated based upon calculated or measured values for known compositions. Measurements using a calibration phantom can advantageously account for system-specific noise, but the effect of calibration methods on the material basis matrix and subsequent quantitative material decomposition has not been experimentally investigated.

Ectopic models for endochondral ossification: comparing pellet and alginate bead culture methods.

Key aspects of native endochondral bone development and fracture healing can be mimicked in mesenchymal stem cells (MSCs) through standard in vitro chondrogenic induction. Exploiting this phenomenon has recently emerged as an attractive technique to engineer bone tissue, however, relatively little is known about the best conditions for doing so. The objective of the present study was to compare the bone-forming capacity and angiogenic induction of hypertrophic cell constructs containing human adipose-derived stem cells (hASCs) primed for chondrogenesis in two different culture systems: high-density pellets and alginate bead hydrogels.

Preparation of fluorescent Au-SiO core-shell nanoparticles and nanorods with tunable silica shell thickness and surface modification for immunotargeting.

Gold-silica (Au-SiO) core-shell nanoparticles (NPs) enable multifunctional properties for in vivo biomedical applications. However, scalable synthesis methods are lacking for the preparation of Au-SiO core-shell NPs less than 30 nm in overall diameter with a tunable silica shell less than 10 nm in thickness. Therefore, we prepared monodispersed Au-SiO core-shell NPs less than 30 nm in overall diameter with a uniform, tunable silica shell ∼1 to 14 nm in thickness using either citrate reduction followed by a modified Stöber method or oleylamine reduction followed by a reverse microemulsion method.

Hafnia (HfO2) nanoparticles as an X-ray contrast agent and mid-infrared biosensor.

The interaction of hafnium oxide (HfO2) nanoparticles (NPs) with X-ray and mid-infrared radiation was investigated to assess the potential as a multifunctional diagnostic probe for X-ray computed tomography (CT) and/or mid-infrared biosensing. HfO2 NPs of controlled size were prepared by a sol-gel process and surface functionalized with polyvinylpyrrolidone, resulting in relatively spherical and monodispersed NPs with a tunable mean diameter in the range of ∼7-31 nm. The X-ray attenuation of HfO2 NPs was measured over 0.

Acellular hydroxyapatite-collagen scaffolds support angiogenesis and osteogenic gene expression in an ectopic murine model: Effects of hydroxyapatite volume fraction.

Acellular hydroxyapatite (HA) reinforced collagen scaffolds were previously reported to induce angiogenesis and osteogenesis after ectopic implantation but the effect of the HA volume fraction was not investigated. Therefore, the objective of this study was to investigate the effect of HA volume fraction on in vivo angiogenesis and osteogenesis in acellular collagen scaffolds containing 0, 20, and 40 vol % HA after subcutaneous ectopic implantation for up to 12 weeks in mice. Endogenous cell populations were able to completely and uniformly infiltrate the entire scaffold within 6 weeks independent of the HA content, but the cell density was increased in scaffolds containing HA versus collagen alone.

Molecular transport in collagenous tissues measured by gel electrophoresis.

Molecular transport in tissues is important for drug delivery, nutrient supply, waste removal, cell signaling, and detecting tissue degeneration. Therefore, the objective of this study was to investigate gel electrophoresis as a simple method to measure molecular transport in collagenous tissues. The electrophoretic mobility of charged molecules in tissue samples was measured from relative differences in the velocity of a cationic dye passing through an agarose gel in the absence and presence of a tissue section embedded within the gel.

Targeted delivery to bone and mineral deposits using bisphosphonate ligands.

The high concentration of mineral present in bone and pathological calcifications is unique compared with all other tissues and thus provides opportunity for targeted delivery of pharmaceutical drugs, including radiosensitizers and imaging probes. Targeted delivery enables accumulation of a high local dose of a therapeutic or imaging contrast agent to diseased bone or pathological calcifications. Bisphosphonates (BPs) are the most widely utilized bone-targeting ligand due to exhibiting high binding affinity to hydroxyapatite mineral.

Contrast-Enhanced X-ray Detection of Microcalcifications in Radiographically Dense Mammary Tissue Using Targeted Gold Nanoparticles.

Breast density reduces the accuracy of mammography, motivating methods to improve sensitivity and specificity for detecting abnormalities within dense breast tissue, but preclinical animal models are lacking. Therefore, the objectives of this study were to investigate a murine model of radiographically dense mammary tissue and contrast-enhanced X-ray detection of microcalcifications in dense mammary tissue by targeted delivery of bisphosphonate-functionalized gold nanoparticles (BP-Au NPs). Mammary glands (MGs) in the mouse mammary tumor virus - polyomavirus middle T antigen (MMTV-PyMT or PyMT) model exhibited greater radiographic density with age and compared with strain- and age-matched wild-type (WT) controls at 6-10 weeks of age.