Mark Grinstaff

Boston University | BU · Department of Biomedical Engineering

Förster resonance energy transfer (FRET) is a widely used and ideal transduction modality for fluorescent based biosensors as it offers high signal to noise with a visibly detectable signal. While intense efforts are ongoing to improve the limit of detection and dynamic range of biosensors based on biomolecule optimization, the selection of and rel...

Objective: A lack of understanding of the mechanisms underlying osteoarthritis progression limits the development of effective long-term treatments. Quantitatively tracking spatiotemporal patterns of cartilage and bone degeneration is critical for assessment of more appropriately targeted OA therapies. In this study, we use contrast-enhanced micro...

Longitudinal bone growth, achieved through endochondral ossification, is accomplished by a cartilaginous structure, the physis or growth plate, comprised of morphologically distinct zones related to chondrocyte function: resting, proliferating and hypertrophic zones. The resting zone is a stem cell-rich region that gives rise to the growth plate, a...

Fluorescence pH Sensing A swellable color‐changing hydrogel dressing featuring a red‐to‐green “traffic light” response to oxygen is developed in article number 2101605 by Conor L. Evens and co‐workers. Using simple macroscopic photography, intensity‐independent quantification of oxygen is enabled though image conversion to the HSB color space, whil...

The role of glucose-6-phosphate dehydrogenase (G6PD) in human cancer is incompletely understood. In a metabolite screening, we observed that inhibition of H3K9 methylation suppressed aerobic glycolysis and enhances the PPP in human mesothelioma cells. Genome-wide screening identified G6PD as an H3K9me3 target gene whose expression is correlated wit...

Peritoneal mesothelioma is an aggressive disease with a median survival of under three years, due to a lack of effective treatment options. Mesothelioma is traditionally considered a “chemoresistant” tumor; however, low intratumoral drug levels coupled with the inability to administer high systemic doses suggests that therapeutic resistance may be...

Mononuclear non-heme iron enzymes are a large class of enzymes catalyzing a wide-range of reactions. In this work, we report that a non-heme iron enzyme in Methyloversatilis thermotolerans, OvoAMtht, has two different activities, as a thiol oxygenase and a sulfoxide synthase. When cysteine is presented as the only substrate, OvoAMtht is a thiol oxy...

Progesterone monitoring is an essential component of in vitro fertilization treatments and reproductive management of dairy cows. Gold-standard biosensors for progesterone monitoring rely on antibodies, which are expensive and difficult to procure. We have developed an alternative transcription factor-based sensor that is superior to conventional p...

Sensor‐integrated wound dressings are emerging tools applicable to a wide variety of medical applications from emergency triage to at‐home monitoring. Uncomfortable, unnecessary wound dressing changes may be avoided by providing quantitative insight into tissue characteristics related to wound healing such as tissue oxygenation, pH, and exudate/tra...

Background Granzyme B is a key effector of cytotoxic T lymphocytes (CTLs), and its expression level positively correlates with the response of patients with mesothelioma to immune checkpoint inhibitor immunotherapy. Whether metabolic pathways regulate Gzmb expression in CTLs is incompletely understood. Methods A tumor-specific CTL and tumor cocult...

We describe the synthesis of poly(glycidyl acetate-co-glycidyl butyrate carbonate)s via the terpolymerization of glycidyl acetate (GA), glycidyl butyrate (GB), and CO2 by a cobalt salen complex in high atom economy. These new non-cytotoxic polycarbonates are pressure-sensitive adhesives, and peel testing shows the adhesive strength ranges from Scot...

Objective To compare CA4+-enhanced micro–computed tomography (microCT) of bovine articular, meniscal, nasal, and auricular cartilage, each of which possesses a different extracellular matrix (ECM) composition and structure. Design The diffusion kinetics of CA4+ in different native cartilage types were assessed over 20 hours. The feasibility of CA4...

Polymerization-induced self-assembly (PISA) is an efficient one-step process to obtain nanomaterials. In this work, aqueous ring-opening polymerization induced self-assembly (ROPISA) of α-amino acid N-carboxyanhydride (NCA) affords controllable well-defined nanoassemblies. ROPISA with the PEG5 kDa-NH2 macroinitiator and either the benzyl-L-glutamat...

Currently, no dressings utilized in burn clinics provide adhesion, hydration or mechanical strength on the same order as human skin as well as the ability to be atraumatically removed. We report the synthesis, characterization, and in vivo evaluation of in situ polymerized and subsequent dissolvable hydrogels as burn wound dressings. Hydrogel dress...

Anticoagulant therapeutics are a mainstay of modern surgery and of clotting disorder management such as venous thrombosis, yet performance and supply limitations exist for the most widely used agent - heparin. Herein we report the first synthesis, characterization, and performance of sulfated poly-amido-saccharides (sulPASs) as heparin mimetics. su...

Diagnostic testing that facilitates containment, surveillance, and treatment of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), or future respiratory viruses, depends on a sample collection device that efficiently collects nasopharyngeal tissue and that can be manufactured on site when an outbreak or public health emergency is declare...

CA4+ is a novel cationic iodinated contrast agent utilized for contrast-enhanced microCT (CECT). In this study, we compared CA4+ CECT for cartilage quantification of unfixed and neutral buffered formalin (NBF)-fixed rabbit distal femur cartilage after 8-, 24- and 30-hours of contrast agent diffusion. The stability of CA4+ binding to cartilage after...

The development of treatments for osteoarthritis (OA) is burdened by the lack of standardized biomarkers of cartilage health that can be applied in clinical trials. We present a novel arthroscopic Raman probe that can “optically biopsy” cartilage and quantify key ECM biomarkers for determining cartilage composition, structure, and material properti...

One of the foremost challenges in translating nanoparticle technologies to the clinic is the requirement to produce materials on a large-scale. Scaling nanoparticle production methods is often non-trivial, and the success of these endeavors is frequently governed by whether or not an intermediate level of production, i.e., “pilot-scale” production,...

The development of treatments for osteoarthritis (OA) is burdened by the lack of standardized biomarkers of cartilage health that can be applied in clinical trials. We present a novel arthroscopic Raman probe that can optically biopsy cartilage and quantify key ECM biomarkers for determining cartilage composition, structure, and material properties...

e16262 Background: Pancreatic adenocarcinoma (PDAC) with peritoneal carcinomatosis (PPC) has the worst median overall survival (mOS) among all PDAC metastasis. Novel therapeutic approaches are needed for PPC. The Dual Endothelin-1/VEGF-signal-peptide Receptor (DEspR) is a cell surface receptor which regulates PDAC tumor cell and cancer stem-like ce...

To prevent the progression of posttraumatic osteoarthritis, assessment of cartilage composition is critical for effective treatment planning. Posttraumatic changes include proteoglycan (PG) loss and elevated water content. Quantitative dual‐energy computed tomography (QDECT) provides a means to diagnose these changes. Here, we determine the potenti...

Background Pancreatic peritoneal carcinomatosis (PPC), with the worst median overall-survival (mOS), epitomizes the incurability of metastatic cancer. Cancer stem cells (CSCs) underpin this incurability. However, inhibitors of CSC-stemness fail to increase mOS in cancer patients despite preclinical tumor-reduction. This shortfall reinforces that pr...

Photon-counting detector computed tomography (PCD-CT) is a modern spectral imaging technique utilizing photon-counting detectors (PCDs). PCDs detect individual photons and classify them into fixed energy bins, thus enabling energy selective imaging, contrary to energy integrating detectors that detects and sums the total energy from all photons dur...

Mitochondrial abnormalities have been noted in lupus, but the causes and consequences remain obscure. Autophagy-related genes ATG5, ATG7 and IRGM have been previously implicated in autoimmune disease. We reasoned that failure to clear defective mitochondria via mitophagy might be a foundational driver in autoimmunity by licensing mitochondrial DNA–...

In the anaerobic ergothioneine biosynthetic pathway, a rhodanese domain-containing enzyme (EanB) activates the hercynine's sp 2 ε-C−H bond and replaces it with a C−S bond to produce ergothioneine. The key intermediate for this trans-sulfuration reaction is the Cys412 persulfide. Substitution of the EanB-Cys412 persulfide with a Cys412 perselenide d...

Direct laser writing (DLW) via two‐photon polymerization is an emerging highly precise technique for the fabrication of intricate cellular scaffolds. Despite recent progress in using two‐photon‐polymerized scaffolds to probe fundamental cell behaviors, new methods to direct and modulate microscale cell alignment and selective cell adhesion using tw...

Fibrosis is the dysregulated biosynthesis of connective tissue that results from persistent infection, high serum cholesterol, surgery, trauma, or prolonged joint immobilization. As a disease that impacts connective tissue, it is prevalent across the body and disrupts normal extracellular and tissue organization. Ultimately, fibrosis impairs the ti...

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...

Myeloid-derived suppressor cells (MDSCs) are immune suppressive cells that massively accumulate under pathological conditions to suppress T cell immune response. Dysregulated cell death contributes to MDSC accumulation, but the molecular mechanism underlying this cell death dysregulation is not fully understood. In this study, we report that neutra...

Lung cancer is the leading cause of cancer deaths worldwide. Unfortunately, high recurrence rates and poor survival remain despite surgical resection and conventional chemotherapy. Local drug delivery systems are a promising intervention for lung cancer treatment with the potential for improved efficacy with reduced systemic toxicity. Here, we desc...

Bioengineering of the human auricle remains a significant challenge, where the complex and unique shape, the generation of high-quality neocartilage, and shape preservation are key factors. Future Regenerative Medicine (RM)-based approaches for auricular cartilage reconstruction will benefit from a smart combination of various strategies. Our appro...

Substitution of flammable, toxic solvents in electrolytes with alternative green options is of significant commercial and environmental interest.

Lysosomes, membrane-bound organelles, play important roles in cellular processes including endocytosis, phagocytosis, and autophagy. Lysosomes maintain cellular homeostasis by generating a highly acidic environment of pH 4.5 - 5.0 and by housing hydrolytic enzymes that degrade engulfed biomolecules. Impairment of lysosomal function, especially in i...

Cationic contrast‐enhanced computed tomography (CECT) is a quantitative imaging technique that characterizes articular cartilage, though its efficacy in differentiating repair tissue from other disease states is undetermined. We hypothesized that cationic CECT attenuation will distinguish between reparative, degenerative, and healthy equine articul...

The lungs have long been considered a desired route for drug delivery but, there is still a lack of strategies to rationally target delivery sites especially in the presence of heterogeneous airway disease. Furthermore, no standardized system has been proposed to rapidly test different ventilation strategies and how they alter the overall and regio...

Objective: miR-122 stimulates proliferation of growth plate chondrocytes whereas miR-451 stimulates terminal differentiation and matrix turnover. Here, we examined the potential of these microRNA as regulators of articular chondrocytes using an in vitro model of osteoarthritis. Methods: miR-122 and miR-451 presence in rat articular cartilage was a...

ConspectusCarbohydrates are ubiquitous in nature, playing vital roles in all organisms ranging from metabolism to intercellular signaling. Polysaccharides, repeating units of small molecule carbohydrates, are hydrophilic, densely functionalized, stereoregular, and rigid macromolecules, and these characteristics are simultaneously advantageous in bi...

Immobilization of biosensors in or on a functional material is critical for subsequent device development and translation to wearable technology. Here we present the development and assessment of an immobilized quantum dot - transcription factor - nucleic acid complex for progesterone detection as a first step toward such device integration. The se...

Osteoarthritis (OA) is a multifactorial disease of the entire joint which afflicts 140 million individuals worldwide regardless of economic or social status. Current clinical treatments for OA primarily center on reducing pain and increasing mobility, and there are limited therapeutic interventions to restore degraded cartilage or slow disease path...

The alkene-isocyanate cycloaddition method affords β-lactams from glycals with high regio- and stereoselectivity, but the factors that determine substrate reactivity are poorly understood. Thus, we synthesized a library of 17 electron-rich alkenes (glycals) with varied protecting groups to systematically elucidate the factors that influence their r...

Particle deposition in the lung during inhalation is of interest to a wide range of biomedical sciences due to the noninvasive therapeutic route to deliver drugs to the lung and other organs via the blood stream. Before reaching the alveoli, particles must transverse the bifurcating network of airways. Computational fluid mechanical studies are oft...

Contrast‐enhanced computed tomography is an emerging diagnostic technique for osteoarthritis. However, the effects of increased water content, as well as decreased collagen and proteoglycan concentrations due to cartilage degeneration, on the diffusion of cationic and non‐ionic agents, are not fully understood. We hypothesize that for a cationic ag...

Osteoarthritis (OA) is a disease of the entire joint, often triggered by cartilage injury, mediated by a cascade of inflammatory pathways involving a complex interplay among metabolic, genetic and enzymatic factors that alter the biochemical composition, microstructure and biomechanical performance. Clinically, OA is characterized by degradation of...

The development of new electrolyte and electrode designs and compositions has led to advances in electrochemical energy-storage (EES) devices over the past decade. However, focusing on either the electrode or electrolyte separately is insufficient for developing safer and more efficient EES devices in various working environments, as the energy-sto...

Immobilization of biosensors on surfaces is a key step toward development of devices for real‐world applications. Here the preparation, characterization, and evaluation of a surface‐bound transcription factor–nucleic acid complex for analyte detection as an alternative to conventional systems employing aptamers or antibodies are described. The sens...

Ergothioneine, a natural longevity vitamin and antioxidant, is a thiol-histidine derivative. Recently, two types of biosynthetic pathways were reported. In the aerobic ergothioneine biosyntheses, non-heme iron enzymes incorporate a sulfoxide to an sp2 C-H bond from trimethyl-histidine (hercynine) through oxidation reactions. In contrast, in the ana...

Cationic computed tomography contrast agents are more sensitive for detecting cartilage degeneration than anionic or non‐ionic agents. However, osteoarthritis‐related loss of proteoglycans and increase in water content contrarily affect the diffusion of cationic contrast agents, limiting their sensitivity. The quantitative dual‐energy computed tomo...

A longstanding goal in science and engineering is to mimic the size, structure, and functionality present in biology with synthetic analogs. Today, synthetic globular polymers of several million molecular weight are unknown, and, yet, these structures are expected to exhibit unanticipated properties due to their size, compactness, and low inter-cha...

Despite the presence of cytotoxic T lymphocytes (CTLs) in the tumor microenvironment, the majority of immunogenic human colon cancers do not respond to immune checkpoint inhibitor immunotherapy and microsatellite instable (MSI) tumors are not naturally eliminated. The molecular mechanism underlying the inactivity of tumor-infiltrating CTLs is unkno...

p>This review highlights current treatments, limitations, and pitfalls in the management of pancreatic cancer and discusses current research in novel targets and drug development to overcome these clinical challenges. We begin with a review of the clinical landscape of pancreatic cancer, including genetic and environmental risk factors, as well as...

Bacteria are an enormous and largely untapped reservoir of biosensing proteins. We describe an approach to identify and isolate bacterial allosteric transcription factors (aTFs) that recognize a target analyte and to develop these TFs into biosensor devices. Our approach utilizes a combination of genomic screens and functional assays to identify an...

Expansile nanoparticles (eNPs) are a promising pH-responsive polymeric drug delivery vehicle, as demonstrated in multiple intraperitoneal cancer models. However, previous delivery routes were limited to intraperitoneal injection and to a single agent, paclitaxel. In this study, we preliminarily evaluate the biodistribution and in vivo toxicity of e...