Publications by authors named "David Shreiber"

Vascular Ehlers-Danlos syndrome (vEDS) arises from mutations in collagen-III, a major structural component of the extracellular matrix (ECM) in vascularized tissues, including blood vessels. Fibrillar collagens form a triple-helix that is characterized by a canonical (Gly-X-Y) sequence. The substitution of another amino acid for Gly within this conserved repeating sequence is associated with several hereditary connective tissue disorders, including vEDS.

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Severe injuries to skeletal muscles, including cases of volumetric muscle loss (VML), are linked to substantial tissue damage, resulting in functional impairment and lasting disability. While skeletal muscle can regenerate following minor damage, extensive tissue loss in VML disrupts the natural regenerative capacity of the affected muscle tissue. Existing clinical approaches for VML, such as soft-tissue reconstruction and advanced bracing methods, need to be revised to restore tissue function and are associated with limitations in tissue availability and donor-site complications.

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Collagens are the most abundant structural proteins in the extracellular matrix of animals and play crucial roles in maintaining the structural integrity and mechanical properties of tissues and organs while mediating important biological processes. Fibrillar collagens have a unique triple helix structure with a characteristic repeating sequence of (Gly-X-Y). Variations within the repetitive sequence can cause misfolding of the triple helix, resulting in heritable connective tissue disorders.

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Electrospray deposition (ESD) is a promising technique for depositing micro-/nano-scale droplets and particles with high quality and repeatability. It is particularly attractive for surface coating of costly and delicate biomaterials and bioactive compounds. While high efficiency of ESD has only been successfully demonstrated for spraying surfaces larger than the spray plume, this work extends its utility to smaller surfaces.

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Click chemistries are efficient and selective reactions that have been leveraged for multi-stage drug delivery. A multi-stage system allows independent delivery of targeting molecules and drug payloads, but targeting first-phase materials specifically to disease sites remains a challenge. Stimuli-responsive systems are an emerging strategy where common pathophysiological triggers are used to target payloads.

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Streptococcus pyogenes-derived recombinant bacterial collagen-like proteins (CLPs) are emerging as a potential biomaterial for biomedical research and applications. Bacterial CLPs form stable triple helices and lack specific interactions with human cell surface receptors, thus enabling the design of novel biomaterials with specific functional attributes. Bacterial collagens have been instrumental in understanding collagen structure and function in normal and pathological conditions.

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Stimuli-responsive biomaterials are an emerging strategy that leverage common pathophysiological triggers to target drug delivery to limit or avoid toxic side effects. Native free radicals, such as reactive oxygen species (ROS), are widely upregulated in many pathological states. We have previously demonstrated that native ROS are capable of crosslinking and immobilizing acrylated polyethylene glycol diacrylate (PEGDA) networks and coupled payloads in tissue mimics, providing evidence for a potential targeting mechanism.

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After muscle loss or injury, skeletal muscle tissue has the ability to regenerate and return its function. However, large volume defects in skeletal muscle tissue pose a challenge to regenerate due to the absence of regenerative elements such as biophysical and biochemical cues, making the development of new treatments necessary. One potential solution is to utilize electroactive polymers that can change size or shape in response to an external electric field.

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Current therapeutic innovations, such as CAR-T cell therapy, are heavily reliant on viral-mediated gene delivery. Although efficient, this technique is accompanied by high manufacturing costs, which has brought about an interest in using alternative methods for gene delivery. Electroporation is an electro-physical, non-viral approach for the intracellular delivery of genes and other exogenous materials.

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Automated cell segmentation is key for rapid and accurate investigation of cell responses. As instrumentation resolving power increases, clear delineation of newly revealed cellular features at the submicron through nanoscale becomes important. Reliance on the manual investigation of myriad small features retards investigation; however, use of deep learning methods has great potential to reveal cell features both at high accuracy and high speed, which may lead to new discoveries in the near term.

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This work reports a suction-based cutaneous delivery method for in vivo DNA transfection. Following intradermal Mantoux injection of plasmid DNA in a rat model, a moderate negative pressure is applied to the injection site, a technique similar to Chinese báguàn and Middle Eastern hijama cupping therapies. Strong GFP expression was demonstrated with pEGFP-N1 plasmids where fluorescence was observed as early as 1 hour after dosing.

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Intracortical neural probes are a key enabling technology for acquiring high fidelity neural signals within the cortex. They are viewed as a crucial component of brain-computer interfaces (BCIs) in order to record electrical activities from neurons within the brain. Smaller, more flexible, polymer-based probes have been investigated for their potential to limit the acute and chronic neural tissue response.

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The mechanical behavior and cortical tension of single cells are analyzed using electrodeformation relaxation. Four types of cells, namely, MCF-10A, MCF-7, MDA-MB-231, and GBM, are studied, with pulse durations ranging from 0.01 to 10 s.

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Electroporation is an electro-physical, non-viral approach to perform DNA, RNA, and protein transfections of cells. Upon application of an electric field, the cell membrane is compromised, allowing the delivery of exogenous materials into cells. Cell viability and electro-transfection efficiency (eTE) are dependent on various experimental factors, including pulse waveform, vector concentration, cell type/density, and electroporation buffer properties.

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Extracellular matrix provides critical signaling context to resident cells through mechanical and bioactive properties. To realize the potential of tissue engineering and regenerative medicine, biomaterials should allow for the independent control of these features. This study investigates a hydrogel system based on thiol-modified hyaluronic acid (HA-S) and polyethylene glycol diacrylate (PEGDA).

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Collagens carry out critical extracellular matrix (ECM) functions by interacting with numerous cell receptors and ECM components. Single glycine substitutions in collagen III, which predominates in vascular walls, result in vascular Ehlers-Danlos syndrome (vEDS), leading to arterial, uterine, and intestinal rupture and an average life expectancy of <50 years. Collagen interactions with integrin αβ are vital for platelet adhesion and activation; however, how these interactions are impacted by vEDS-associated mutations and by specific amino acid substitutions is unclear.

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Targeted drug delivery is a promising approach to enhance the accumulation of therapies in diseased tissues while limiting off-site effects. Ligand-receptor interactions are traditionally identified to deliver therapies, and although specific, this can be costly and often suffers from limited sensitivity. An emerging approach is to target intermediary species that modulate disease progression.

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Multicellular aggregates are an excellent model system to explore the role of tissue biomechanics in specifying multicellular reorganization during embryonic developments and malignant invasion. Tissue-like spheroids, when subjected to a compressive force, are known to exhibit liquid-like behaviors at long timescales (hours), largely because of cell rearrangements that serve to effectively dissipate the applied stress. At short timescales (seconds to minutes), before cell rearrangement, the mechanical behavior is strikingly different.

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Astroglia are well known for their role in propagating secondary injury following brain trauma. Modulation of this injury cascade, including inflammation, is essential to repair and recovery. Mesenchymal stromal cells (MSCs) have been demonstrated as trophic mediators in several models of secondary CNS injury, however, there has been varied success with the use of direct implantation due to a failure to persist at the injury site.

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As a biomaterial, collagen has been used throughout tissue engineering and regenerative medicine. Collagen is native to the body, is highly biocompatible, and naturally promotes cell adhesion and regeneration. However, collagen fibers and the inherent weak mechanical properties of collagen hydrogels interfere with further development of collagen as a bio-ink.

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Objective: Despite the feasibility of short-term neural recordings using implantable microelectrodes, attaining reliable, chronic recordings remains a challenge. Most neural recording devices suffer from a long-term tissue response, including gliosis, at the device-tissue interface. It was hypothesized that smaller, more flexible intracortical probes would limit gliosis by providing a better mechanical match with surrounding tissue.

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To create musculoskeletal tissue scaffolds for functional integration into host tissue, myotubes must be properly aligned with native tissue and spur the formation of neuromuscular junctions. However, our understanding of myoblast differentiation in response to structural alignment is incomplete. To examine how substrate anisotropy mediates myotube differentiation, we studied C2C12 myoblasts grown on aligned collagen substrates in the presence or absence of agrin.

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The construction of biomaterials with which to limit the growth of cells or to limit the adsorption of proteins is essential for understanding biological phenomena. Here, we describe a novel method to simply and easily create thin layers of poly (2-hydroxyethyl methacrylate) (p-HEMA) for protein and cellular patterning via etching with ethanol and microfluidic devices. First, a cell culture surface or glass coverslip is coated with p-HEMA.

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A novel quantitative volumetric spreading index (VSI) is defined that depends on the total distance between object voxels and the contact surface plane in three-dimensional (3D) space. The VSI, which ranges from 0 to 1, is rotationally invariant around the z-axis. VSI can be used to quantify the degree of individual cell spreading, which is important for analysis of cell interactions with their environment.

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Background: Dispersal of glioblastoma (GBM) cells leads to recurrence and poor prognosis. Accordingly, molecular pathways involved in dispersal are potential therapeutic targets. The mitogen activated protein kinase/extracellular signal regulated kinase (MAPK/ERK) pathway is commonly dysregulated in GBM, and targeting this pathway with MEK inhibitors has proven effective in controlling tumor growth.

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