Mark GrinstaffBoston University | BU · Department of Biomedical Engineering
Mark Grinstaff
Doctor of Philosophy
www.grinstaff.org
About
568
Publications
88,303
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
29,015
Citations
Introduction
Mark Grinstaff’s inventive scientific contributions span biomedical engineering, biological engineering, nanotechnology, chemistry, and medicine, producing transformational discoveries and technologies unique to the convergence of these fields. He has developed new paradigms for translating rigorous, quantitative academic work, which promotes intellectual progress, economic growth, and improved clinical outcomes.
Additional affiliations
September 2003 - present
Education
September 1987 - May 1992
September 1983 - May 1987
Publications
Publications (568)
Image analysis of subcellular structures and biological processes relies on specific, context-dependent pipelines, which are labor-intensive, constrained by the intricacies of the specific biological system, and inaccessible to broader applications. Here we introduce the application of dispersion indices, a statistical tool traditionally employed b...
The ability of articular cartilage to withstand significant mechanical stresses during activities, such as walking or running, relies on its distinctive structure. Integrating detailed tissue properties into subject-specific biomechanical models is challenging due to the complexity of analyzing these characteristics. This limitation compromises the...
The use of modified nucleotides to suppress the interferon response and maintain translation of self-amplifying RNA (saRNA), which has been achieved for mRNA, has not yet succeeded. We identify modified nucleotides that, when substituted at 100% in saRNA, confer innate immune evasion and robust long-term protein expression, and when formulated as a...
Joint kinematic instability, arising from congenital or acquired musculoskeletal pathoanatomy or from imbalances in anabolism and catabolism induced by pathophysiological factors, leads to deterioration of the composition, structure and function of cartilage and, ultimately, progression to osteoarthritis (OA). Alongside articular cartilage degenera...
Type 2 diabetes (T2D), a prevalent metabolic disorder lacking effective treatments, is associated with lysosomal acidification dysfunction, as well as autophagic and mitochondrial impairments. Here, we report a series of biodegradable poly(butylene tetrafluorosuccinate-co-succinate) polyesters, comprising a 1,4-butanediol linker and varying ratios...
Cationic contrast‐enhanced computed tomography (CECT) capitalizes on increased contrast agent affinity to the charged proteoglycans in articular cartilage matrix to provide quantitative assessment of proteoglycan content with enhanced images. While high resolution microCT has demonstrated success, we investigate cationic CECT use in longitudinal in...
Significant advancements in the syntheses of cyclobutane containing small molecules and polymers are described in the last 15 years. Small molecule cyclobutanes are under investigation for their diverse pharmacological activities,...
We report the relationships between linear vs. network polymer architecture and biomechanical outcomes including lubrication and cushioning when the polymers are applied to the surface of articulating knee cartilage. Aqueous formulations of the bioinspired polymer poly(2-methacryloyloxylethyl phosphorylcholine) (pMPC) exhibit tuneable rheological p...
Self-amplifying RNA (saRNA) will revolutionize vaccines and in situ therapeutics by enabling protein expression for longer duration at lower doses. However, a major barrier to saRNA efficacy is the potent early interferon response triggered upon cellular entry, resulting in saRNA degradation and translational inhibition. Substitution of mRNA with m...
In cancer, solid stresses impede the delivery of therapeutics to tumours and the trafficking and tumour infiltration of immune cells. Understanding such consequences and the origin of solid stresses requires their probing in vivo at the cellular scale. Here we report a method for performing volumetric and longitudinal measurements of solid stresses...
Cartilage and synovial fluid are challenging to observe separately in native computed tomography (CT). We report the use of triple contrast agent (bismuth nanoparticles, CA4+, and gadoteridol) to image and segment cartilage in cadaveric knee joints with a clinical CT scanner. We hypothesize that bismuth nanoparticles will remain in synovial fluid w...
Type 2 diabetes (T2D) is one of the most common metabolic disorders worldwide without effective treatments. Lysosomal acidification impairment, autophagy defect, and mitochondrial dysfunction all associate with T2D, although the exact pathogenic mechanisms remain under investigation. Here, we report a series of biodegradable poly(butylene tetrafluo...
We report the synthesis of block copolymers of monomethoxylated polyethylene glycol and poly(glycerol carbonate) (mPEG-b-PGC) via the ring-opening polymerization of benzyl glycidyl ether, monomethoxylated polyethylene glycol, and carbon dioxide using a cobalt salen catalyst. The resulting block copolymers display high polymer/cyclic carbonate selec...
Background:
The intersection of synthetic biology and biomaterials promises to enhance safety and efficacy in novel therapeutics. Both fields increasingly employ Boolean logic, which allows for specific therapeutic outputs (e.g., drug release, peptide synthesis) in response to inputs such as disease markers or bio-orthogonal stimuli. Examples incl...
SARS-CoV-2 can infect cells through endocytic uptake, a process which can be targeted by inhibition of lysosomal proteases. However, clinically this approach fared poorly with an oral regimen of hydroxychloroquine that was accompanied by significant toxicity due to off-target effects. We rationalized that an organelle-targeted approach will avoid t...
Cancer initiation and progression drastically alter the microenvironment at the interface between healthy and malignant tissue. This site, termed the peritumor, bears unique physical and immune attributes that together further promote tumor progression through interconnected mechanical signaling and immune activity. In this review, we describe the...
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. High levels of free fatty acids in the liver impair hepatic lysosomal acidification and reduce autophagic flux. We investigate whether restoration of lysosomal function in NAFLD recovers autophagic flux, mitochondrial function, and insulin sensitivity. Here, we...
Pressure sensitive adhesives are components of everyday products found in homes, offices, industries, and hospitals. Serving the general purpose of fissure repair and object fixation, pressure sensitive adhesives indiscriminately bind surfaces, as long as contact pressure is administered at application. With that being said, the chemical and materi...
Millions of individuals undergo gastrointestinal (GI) tract surgeries each year with common postoperative complications including bleeding, perforation, anastomotic leakage, and infection. Today, techniques such as suturing and stapling seal internal wounds, and electrocoagulation stops bleeding. These methods induce secondary damage to the tissue...
Nanoparticle biodistribution in vivo is an essential component to the success of nanoparticle-based drug delivery systems. Previous studies with fluorescently labeled expansile nanoparticles, or "eNPs", demonstrated a high specificity of eNPs to tumors that is achieved through a materials-based targeting strategy. However, fluorescent labeling tech...
Burn wounds result from exposure to hot liquids, chemicals, fire, electric discharge or radiation. Wound severity ranges from first-degree injury, which is superficial, to fourth-degree injury, which exposes bone, tendons and muscles. Rapid assessment of burn depth and accurate wound management in the outpatient setting is critical to prevent injur...
Electrospun nanofibers are a 3D scaffold of choice for many drug delivery devices due to their high surface area, significant capacity for drug payload, ease of in situ placement, and scalable manufacture. Herein, we report the synthesis of polymeric, pH-responsive nanofiber buttresses via electrospinning. The homopolymer is comprised of an acrylic...
Pressure-sensitive adhesives are familiar household items spanning applications in everyday repair, office supplies and topical wound care. Through innovations in material and polymer science, pressure-sensitive adhesives will advance from current commodity to new specialty materials with resulting new clinical uses and improved patient care.
Rieske-type non-heme iron oxygenases/oxidases catalyze a wide range of transformations. Their applications in bioremediation or biocatalysis face two key barriers: the need of expensive NAD(P)H as a reductant and a proper reductase to mediate the electron transfer from NAD(P)H to the oxygenases. To bypass the need of both the reductase and NAD(P)H,...
Background
Drug-loaded meshes offer a promising delivery strategy for the prevention of local recurrence. Patient-derived xenograft (PDX) models are representative of individual patient tumors and predictive of clinical outcomes.
Methods
A PDX model was established in NSG (NOD-scid IL2Rgammanull) mice using tumor tissue from a patient with aggress...
Substantial advances in biotherapeutics are distinctly lacking for musculoskeletal diseases. Musculoskeletal diseases are biomechanically complex and localized, highlighting the need for novel therapies capable of addressing these issues. All frontline treatment options for arthrofibrosis, a debilitating musculoskeletal disease, fail to treat the d...
Glycolipid biosurfactants are of interest for various industry sectors. We report the synthesis and characterization of enantiopure poly-amido-saccharides (PASs) containing myristoyl (C14), palmitoyl (C16), or stearoyl (C18) terminal chain lengths as mimetics of glycolipid biosurfactants. These amphiphilic polymers are water soluble, adopt a helica...
Surgery is the only potentially curative treatment for localized soft-tissue sarcomas. However, for sarcomas arising in the retroperitoneum, locoregional recurrence rates are 35% to 59% despite resection. Doxorubicin (DOX) is the standard first-line systemic chemotherapy for advanced soft-tissue sarcoma, yet its intravenous administration yields li...
Transfection of chondrocytes with microRNA-451(miR-451), present in growth zone cartilage of the growth plate, upregulates production of enzymes association with extracellular matrix degradation. miR-451 is also present in articular cartilage and exacerbates IL-1β effects in articular chondrocytes. Moreover, when osteoarthritis (OA) was induced in...
Ring opening polymerization (ROP) of lactams is a highly efficient and versatile method to synthesize polyamides. Within the last ten years, significant advances in polymerization methodology and monomer diversity are ushering in a new era of polyamide chemistry. We begin with a discussion of polymerization techniques including the most widely used...
Risk of locoregional recurrence after sarcoma resection is high, increasing both morbidity and mortality. Intraoperative implantation of paclitaxel (PTX)-eluting polymer films locally delivers sustained, supratherapeutic PTX concentrations to the tumor bed that are not clinically feasible with systemic therapy, thereby reducing recurrence and impro...
β-Glucans are of significant interest due to their potent antitumor and immunomodulatory activities. Nevertheless, the difficulty in purification, structural heterogenicity, and limited solubility impede the development of structure-property relationships and translation to therapeutic applications. Here, we report the synthesis of a new class of (...
Fas ligand (FasL), expressed on the surface of activated cytotoxic T lymphocytes (CTLs), is the physiological ligand for the cell surface death receptor, Fas. The Fas-FasL engagement initiates diverse signaling pathways, including the extrinsic cell death signaling pathway, which is one of the effector mechanisms that CTLs use to kill tumor cells....
Arthrofibrosis, or rigid contracture of major articular joints, is a significant morbidity of many neurodegenerative disorders. The pathogenesis depends on the mechanism and severity of the precipitating neuromuscular disorder. Most neuromuscular disorders, whether spastic or hypotonic, culminate in decreased joint range of motion. Limited range of...
A lack of understanding of the mechanisms underlying osteoarthritis (OA) 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‐comput...
We report the synthesis of diblock poly-amido-saccharides (PASs) by sequential addition of variably protected glucose and galactose monomers via living anionic ring-opening polymerization. Diblock polymers with varied polymer length, hydrophobic to hydrophilic ratio, and stereochemistry of hydrophilic component were synthesized, characterized by NM...
Solid stress, one of the physical hallmarks of cancer, affects trafficking and infiltration of immune cells, promotes metastasis and tumorigenic pathways, and impedes therapeutic delivery. Despite these clinical ramifications, questions remain regarding the origins and consequences of solid stresses and the differential response of tumor versus nor...
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...
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...
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...
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...
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...
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...