Abhay Pandit | National University of Ireland, Galway (original) (raw)
Papers by Abhay Pandit
Biomaterials Science
The study shows that although pIL-10/pDCN therapy are individually able to suppress TGF-β1/β2, on... more The study shows that although pIL-10/pDCN therapy are individually able to suppress TGF-β1/β2, only the combined overexpression of both transgenes was efficacious in suppressing TGF-β1/β2 and concurrently sustaining the upregulation of TGF-β3.
Pharmaceutics
We report a physiologically stable and cytocompatible glucose-responsive nonviral gene delivery s... more We report a physiologically stable and cytocompatible glucose-responsive nonviral gene delivery system made up of boronate functionalized polymeric material. Herein, we utilize boronate cis-diol interactions to develop a glucose-responsive submicron particle (SMP) system. The stability of the boronate interaction at a physiological pH was achieved by copolymerization of dimethyl aminoethyl methacrylate (DMAEMA) with acrylamidophenylboronic acid (AAPBA) and the formation of a complex with polyvinylalcohol (PVA) which is governed by cis-diol interactions. The shift in hydrodynamic diameter of SMPs was observed and correlated with increasing glucose concentrations at a physiological pH. Optimal transfection was observed for a 5 µg dose of the gaussia luciferase reporter gene in NIH3T3 cells without any adverse effect on cellular viability. The destabilization of the AAPBA–PVA complex by interacting with glucose allowed the release of encapsulated bovine serum albumin (BSA) in a glucose...
Galway, Ireland Monodispersed Micro and Nanospheres: Fabrication of Collagen-based Reservoir Syst... more Galway, Ireland Monodispersed Micro and Nanospheres: Fabrication of Collagen-based Reservoir Systems Gianluca Fontana, Shane Browne, Hongliang Cao, Mohammad Abu-Rub, Dimitrios Zeugolis, Wenxin Wang, Abhay Pandit* Network of Excellence for Functional Biomaterials, National University of Ireland Galway *abhay.pandit@nuigalway.ie Introduction One important aspect in tissue engineering is the release of bioactive factors. Therefore, the loading properties of the delivery system can be a determinant for the bioactivity. The hypothesis behind this study is that a reservoir system which has a spherical shape that has the optimal surface/volume ratio can be developed using a template fabrication method. The overall objective of this work was to identify a method that allows tight size control over the spheres with high efficiency and reproducibility. This study highlights the comparison of different methods.
Introduction: Hyaluronic acid (HA) is an anionic biopolymer composed of alternating disaccharide ... more Introduction: Hyaluronic acid (HA) is an anionic biopolymer composed of alternating disaccharide units of D-glucuronic acid and Nacetyl-D-glucosamine with (14)interglycosidic linkage [1]. It is the only nonsulfated glycosaminoglycan (GAG) that is abundant in the synovial fluid and extracellular matrix (ECM) [1-2]. The over all goal of this study is to fabricate and characterize nanospheres based on hyaluronan using an ionic gelation method for therapeutic sustained and controlled gene delivery. Materials and Methods: Plasmid DNA loaded HA nanospheres were prepared by ionic gelation followed by cross-linking method. In the present study nanospheres were prepared by 20% w/v sodium sulphate and cross linked by various crosslinkers i.e. glutaraldehyde, EDC/NHS and 4 arm star PEG. Nanospheres were characterized for particle size, zeta potential, SEM, TEM and in vitro DNA release. FITC-dextran loaded Nanospheres were also prepared following the same method and used for cell uptake studi...
T issue engineering (TE) has the potential of improving the quality of life for many thousands of... more T issue engineering (TE) has the potential of improving the quality of life for many thousands of people throughout the world. One particular area which presents an exciting challenge in this field is the repair and regeneration of cartilage where traumatic injuries and arthritis result in pain and restriction of movement. In order to achieve this goal of tissue engineering cartilage, there are three necessary components: cells for the generation of tissue, a scaffold to support growth and that degrades as the extracellular matrix is generated and a bioactive factor to stimulate the correct biological signals in vivo for tissue growth and integration with native cartilage. Over the last number of years there has been significant interest in progenitor stem cells for TE applications. Mesenchymal stem cells (MSCs) have been shown to differentiate into a range of tissues including bone, cartilage, muscle, tendon, skin and fat. Furthermore, a number of biocompatible biodegradable materi...
Signal Transduction and Targeted Therapy
Galway, Ireland Fibrin Microspheres Extend the Gene Delivery Capacity in a Fibrin Scaffold Manges... more Galway, Ireland Fibrin Microspheres Extend the Gene Delivery Capacity in a Fibrin Scaffold Mangesh M Kulkarni, Udo Greiser, Timothy O’Brien and Abhay Pandit Network of Excellence for Functional Biomaterials; Regenerative Medicine Institute; National University of Ireland, Galway, Ireland Abhay.pandit@nuigalway.ie Introduction The greatest challenge for non-viral vectors is the sustained release of a sufficient amount of a gene at the disease site to accomplish therapeutic benefit. Previously, we have shown that sustained delivery of two reporter genes (at a total dose of 5 μg pDNA) is feasible in a rabbit ear ulcer model up to 7 days via a fibrin scaffoldlipoplex system. The objective of this study was to enhance the capacity of the fibrin scaffold to carry higher amounts of DNA complexes. We have hypothesized that fibrin scaffold augmented by fibrin microspheres (FM) can be fabricated to encapsulate higher amounts of DNAcomplexes and that the DNA complexes remain intact and functio...
Quantification of eluted nucleic acids is critical in characterizing biomaterial based non-viral ... more Quantification of eluted nucleic acids is critical in characterizing biomaterial based non-viral gene-delivery systems. The standard quantification assay uses an intercalating fluorescent dye such as PicoGreen®. However, this technique was developed for unbound DNA and the current trend in gene delivery is to condense DNA with transfection reagents which interfere with intercalation. Here, DNA was permanently labeled with the fluorescent dye Cy5 prior to complexation in an alternative technique hypothesized to allow improved quantification of eluted DNA. The two methods were compared by quantifying the elution of six different varieties of DNA complexes from a collagen scaffold. After seven days of elution, PicoGreen® only allowed detection of three types of complexes while the fluorescent labeling technique detected all six varieties including poly(ethylene imine) and poly-L-Lysine complexes, allowing quantification of elution in all samples. Thus, the technique described in this study allows reliable quantification of DNA independent of complexation state.
INTRODUCTION and DISCUSSION: Textbook definitions of cartilage generally identify three classes o... more INTRODUCTION and DISCUSSION: Textbook definitions of cartilage generally identify three classes of histologically distinguishable cartilage: hyaline, fibroand elasticcartilage. However a survey of cartilage histology throughout vertebrate lineages illustrates that cartilage as a tissue type exhibits an entire spectrum of histological diversity. Indeed, the notochord remains ambiguous as to whether or not it can be considered a type of cartilage despite expression of various cartilage-specific markers (see below) and its persistence into adulthood in various lineages. In addition, examples of cellular cartilages are found in a number of invertebrate lineages, including arthropods, annelids, and molluscs. Although the existence of these tissues outside of the vertebrate lineages is known, the relationship between invertebrate and vertebrate cartilage is at best unclear. A strong vertebrate fossil record gives much information about the evolution of mineralized tissues, but has little ...
Biochemical Society Transactions
The extracellular matrix (ECM) dynamics in tumour tissue are deregulated compared to the ECM in h... more The extracellular matrix (ECM) dynamics in tumour tissue are deregulated compared to the ECM in healthy tissue along with disorganized architecture and irregular behaviour of the residing cells. Nitric oxide (NO) as a pleiotropic molecule exerts different effects on the components of the ECM driving or inhibiting augmented angiogenesis and tumour progression and tumour cell proliferation and metastasis. These effects rely on the concentration of NO within the tumour tissue, the nature of the surrounding microenvironment and the sensitivity of resident cells to NO. In this review article, we summarize the recent findings on the correlation between the levels of NO and the ECM components towards the modulation of tumour angiogenesis in different types of cancers. These are discussed principally in the context of how NO modulates the expression of ECM proteins resulting in either the promotion or inhibition of tumour growth via tumour angiogenesis. Furthermore, the regulatory effects o...
International Journal of Molecular Sciences
Mesenchymal stem cells (MSCs) can improve chronic wound healing; however, recent studies suggest ... more Mesenchymal stem cells (MSCs) can improve chronic wound healing; however, recent studies suggest that the therapeutic effect of MSCs is mediated mainly through the growth factors and cytokines secreted by these cells, referred to as the MSC secretome. To overcome difficulties related to the translation of cell therapy into clinical use such as efficacy, safety and cost, we propose a hydrogel loaded with a secretome from the recently established human adipose tissue mesenchymal stem cell line (HATMSC2) as a potential treatment for chronic wounds. Biocompatibility and biological activity of hydrogel-released HATMSC2 supernatant were investigated in vitro by assessing the proliferation and metabolic activity of human fibroblast, endothelial cells and keratinocytes. Hydrogel degradation was measured using hydroxyproline assay while protein released from the hydrogel was assessed by interleukin-8 (IL-8) and macrophage chemoattractant protein-1 (MCP-1) ELISAs. Pro-angiogenic activity of t...
Advanced Science
Abstract Chronic limb threatening ischemia (CLTI) is a severe condition defined by the blockage o... more Abstract Chronic limb threatening ischemia (CLTI) is a severe condition defined by the blockage of arteries in the lower extremities that leads to the degeneration of blood vessels and is characterized by the formation of non‐healing ulcers and necrosis. The gold standard therapies such as bypass and endovascular surgery aim at the removal of the blockage. These therapies are not suitable for the so‐called “no option patients” which present multiple artery occlusions with a likelihood of significant limb amputation. Therefore, CLTI represents a significant clinical challenge, and the efforts of developing new treatments have been focused on stimulating angiogenesis in the ischemic muscle. The delivery of pro‐angiogenic nucleic acid, protein, and stem cell‐based interventions have limited efficacy due to their short survival. Engineered biomaterials have emerged as a promising method to improve the effectiveness of these latter strategies. Several synthetic and natural biomaterials are tested in different formulations aiming to incorporate nucleic acid, proteins, stem cells, macrophages, or endothelial cells in supportive matrices. In this review, an overview of the biomaterials used alone and in combination with growth factors, nucleic acid, and cells in preclinical models is provided and their potential to induce revascularization and regeneration for CLTI applications is discussed.
ACS Nano
Cell membrane-coated (CMC) mimics are micro/nanosystems that combine an isolated cell membrane an... more Cell membrane-coated (CMC) mimics are micro/nanosystems that combine an isolated cell membrane and a template of choice to mimic the functions of a cell. The design exploits its physicochemical and biological properties for therapeutic applications. The mimics demonstrate excellent biological compatibility, enhanced biointerfacing capabilities, physical, chemical, and biological tunability, ability to retain cellular properties, immune escape, prolonged circulation time, and protect the encapsulated drug from degradation and active targeting. These properties and the ease of adapting them for personalized clinical medicine have generated a significant research interest over the past decade. This review presents a detailed overview of the recent advances in the development of cell membrane-coated (CMC) mimics. The primary focus is to collate and discuss components, fabrication methodologies, and the significance of physiochemical and biological characterization techniques for validating a CMC mimic. We present a critical analysis of the two main components of CMC mimics: the template and the cell membrane and mapped their use in therapeutic scenarios. In addition, we have emphasized on the challenges associated with CMC mimics in their clinical translation. Overall, this review is an up to date toolbox that researchers can benefit from while designing and characterizing CMC mimics.
Journal of Biomedical Materials Research Part B: Applied Biomaterials
Abstract Interstitial cystitis (IC) is a progressive bladder disease characterized by increased u... more Abstract Interstitial cystitis (IC) is a progressive bladder disease characterized by increased urothelial permeability, inflammation of the bladder with abdominal pain. While there is no consensus on the etiology of the disease, it was believed that restoring the barrier between urinary solutes and (GAG) urothelium would interrupt the progression of this disease. Currently, several treatment options include intravesical delivery of hyaluronic acid (HA) and/or chondroitin sulfate solutions, through a catheter to restore the urothelial barrier, but have shown limited success in preclinical, clinical trials. Herein we report for the first time successful engineering and characterization of biphasic system developed by combining cross‐linked hyaluronic acid and naïve HA solution to decrease inflammation and permeability in an in vitro model of interstitial cystitis. The cross‐linking of HA was performed by 4‐arm‐polyethyeleneamine chemistry. The HA formulations were tested for their viscoelastic properties and the effects on cell metabolism, inflammatory markers, and permeability. Our study demonstrates the therapeutic effects of different ratios of the biphasic system and reports their ability to increase the barrier effect by decreasing the permeability and alteration of cell metabolism with respect to relative controls. Restoring the barrier by using biphasic system of HA therapy may be a promising approach to IC.
Frontiers in Bioengineering and Biotechnology
The potential biomedical applications of nanodiamond have been considered over the last few decad... more The potential biomedical applications of nanodiamond have been considered over the last few decades. However, there is still uncertainty regarding the extent to which the surface characteristics of this material can influence potential applications. The present study investigated the effects of surface characteristics alongside the prospective of improving nanodiamond production using cold plasma and microwave technologies for the surface tailoring of the nanocarbons. Numerous approaches were applied to purify, refine and modify a group of nanosized diamonds at each step of their production cycle: from the detonation soot as the initial raw material to already certified samples. The degree of surface changes were deliberately performed slowly and kept at different non-diamond carbon presence stages, non-carbon elemental content, and amount converted superficial moieties. In total, 21 treatment procedures and 35 types of nanosize diamond products were investigated. In addition cultur...
Journal of Neuroinflammation
Background Neuroinflammation is an underlying pathology of all neurological conditions, the under... more Background Neuroinflammation is an underlying pathology of all neurological conditions, the understanding of which is still being comprehended. A specific molecular pathway that has been overlooked in neuroinflammation is glycosylation (i.e., post-translational addition of glycans to the protein structure). N-glycosylation is a specific type of glycosylation with a cardinal role in the central nervous system (CNS), which is highlighted by congenital glycosylation diseases that result in neuropathological symptoms such as epilepsy and mental retardation. Changes in N-glycosylation can ultimately affect glycoproteins’ functions, which will have an impact on cell machinery. Therefore, characterisation of N-glycosylation alterations in a neuroinflammatory scenario can provide a potential target for future therapies. Methods With that aim, the unilateral intrastriatal injection of lipopolysaccharide (LPS) in the adult rat brain was used as a model of neuroinflammation. In vivo and post-m...
JOR SPINE
Spine‐related infections, such as vertebral osteomyelitis, discitis, or spondylitis, are rare dis... more Spine‐related infections, such as vertebral osteomyelitis, discitis, or spondylitis, are rare diseases that mostly affect adults, and are usually of hematogenous origin. The incidence of this condition has gradually risen in recent years because of increases in spine‐related surgery and hospital‐acquired infections, an aging population, and intravenous (IV) drug use. Spine infections are most commonly caused by Staphylococcus aureus, while other systemic infections such as tuberculosis and brucellosis can also cause spondylitis. Various animal models of vertebral osteomyelitis and associated infections have been investigated in mouse, rat, chicken, rabbit, dog, and sheep models by hematogenous and direct inoculation in surgery, each with their strengths and limitations. This review is the first of its kind to concisely analyze the various existing animal models used to reproduce clinically relevant models of infection. Spine‐related infection models must address the unique anatomy of the spine, the avascular nature of its structures and tissues and the consequences of tissue destruction such as spinal cord compression. Further investigation is necessary to elucidate the specific mechanisms of host‐microbe response to inform antimicrobial therapy and administration techniques in a technically demanding body cavity. Small‐animal models are not suitable for large instrumentation, and difficult IV access thwarts antibiotic administration. In contrast, large‐animal models can be implanted with clinically relevant instrumentation and are resilient to repeat procedures to study postoperative infection. A canine model of infection offers a unique opportunity to design and investigate antimicrobial treatments through recruitment a rich population of canine patients, presenting with a natural disease that is suitable for randomized trials.
Advanced Healthcare Materials
Academic institutions are becoming more focused on translating new technologies for clinical appl... more Academic institutions are becoming more focused on translating new technologies for clinical applications. A transition from "bench to bedside" is often described to take basic research concepts and methods to develop a therapeutic or diagnostic solution with proven evidence of efficacy at the clinical level while also fulfilling regulatory requirements. The regulatory environment is evolving in Europe with transition and grace periods for the full enforcement of the Medical Device Regulation 2017/745 (MDR), replacing the Medical Device Directive 93/42/EEC (MDD). These new guidelines increase demands for scientific, technical, and clinical data with reduced capacity in regulatory bodies creating uncertainty in future product certification. Academic translational activities will be uniquely affected by this new legislation. The barriers and threats to successful translation in academia can be overcome by strong clinical partnerships, close-industrial collaborations, and entrepreneurial programs, enabling continued product development to overcome regulatory hurdles, reassuring their foothold of medical device development.
European Cells and Materials
Intervertebral disc (IVD) degeneration causes low-back pain through disc compression, prolapse an... more Intervertebral disc (IVD) degeneration causes low-back pain through disc compression, prolapse and herniation. Inflammation of the IVD and subsequent degeneration produce altered glycosylation profiles in several animal models of IVD injury and ageing, although the function of this altered glycosylation pattern in a human is unknown. Altered N-glycome, specifically sialylated and fucosylated N-glycosylation motif expression, might play a role in inflammation and disease progression. Healthy (foetal and adolescent idiopathic scoliosis) and degenerated (lumbar degeneration) human IVD glycosylation patterns were studied using lectin histochemistry. Small-molecule fluorinated sugar analogues (3Fax-Peracetyl Neu5Ac; 2F-Peracetyl-Fucose) were used to inhibit sialylation and fucosylation in an in vitro model of inflammation, to investigate their effects on the glycosignature, cell metabolism, extracellular matrix synthesis and cell migration. The effects of interleukin (IL)-1β, tumour necr...
Biomaterials Science
The study shows that although pIL-10/pDCN therapy are individually able to suppress TGF-β1/β2, on... more The study shows that although pIL-10/pDCN therapy are individually able to suppress TGF-β1/β2, only the combined overexpression of both transgenes was efficacious in suppressing TGF-β1/β2 and concurrently sustaining the upregulation of TGF-β3.
Pharmaceutics
We report a physiologically stable and cytocompatible glucose-responsive nonviral gene delivery s... more We report a physiologically stable and cytocompatible glucose-responsive nonviral gene delivery system made up of boronate functionalized polymeric material. Herein, we utilize boronate cis-diol interactions to develop a glucose-responsive submicron particle (SMP) system. The stability of the boronate interaction at a physiological pH was achieved by copolymerization of dimethyl aminoethyl methacrylate (DMAEMA) with acrylamidophenylboronic acid (AAPBA) and the formation of a complex with polyvinylalcohol (PVA) which is governed by cis-diol interactions. The shift in hydrodynamic diameter of SMPs was observed and correlated with increasing glucose concentrations at a physiological pH. Optimal transfection was observed for a 5 µg dose of the gaussia luciferase reporter gene in NIH3T3 cells without any adverse effect on cellular viability. The destabilization of the AAPBA–PVA complex by interacting with glucose allowed the release of encapsulated bovine serum albumin (BSA) in a glucose...
Galway, Ireland Monodispersed Micro and Nanospheres: Fabrication of Collagen-based Reservoir Syst... more Galway, Ireland Monodispersed Micro and Nanospheres: Fabrication of Collagen-based Reservoir Systems Gianluca Fontana, Shane Browne, Hongliang Cao, Mohammad Abu-Rub, Dimitrios Zeugolis, Wenxin Wang, Abhay Pandit* Network of Excellence for Functional Biomaterials, National University of Ireland Galway *abhay.pandit@nuigalway.ie Introduction One important aspect in tissue engineering is the release of bioactive factors. Therefore, the loading properties of the delivery system can be a determinant for the bioactivity. The hypothesis behind this study is that a reservoir system which has a spherical shape that has the optimal surface/volume ratio can be developed using a template fabrication method. The overall objective of this work was to identify a method that allows tight size control over the spheres with high efficiency and reproducibility. This study highlights the comparison of different methods.
Introduction: Hyaluronic acid (HA) is an anionic biopolymer composed of alternating disaccharide ... more Introduction: Hyaluronic acid (HA) is an anionic biopolymer composed of alternating disaccharide units of D-glucuronic acid and Nacetyl-D-glucosamine with (14)interglycosidic linkage [1]. It is the only nonsulfated glycosaminoglycan (GAG) that is abundant in the synovial fluid and extracellular matrix (ECM) [1-2]. The over all goal of this study is to fabricate and characterize nanospheres based on hyaluronan using an ionic gelation method for therapeutic sustained and controlled gene delivery. Materials and Methods: Plasmid DNA loaded HA nanospheres were prepared by ionic gelation followed by cross-linking method. In the present study nanospheres were prepared by 20% w/v sodium sulphate and cross linked by various crosslinkers i.e. glutaraldehyde, EDC/NHS and 4 arm star PEG. Nanospheres were characterized for particle size, zeta potential, SEM, TEM and in vitro DNA release. FITC-dextran loaded Nanospheres were also prepared following the same method and used for cell uptake studi...
T issue engineering (TE) has the potential of improving the quality of life for many thousands of... more T issue engineering (TE) has the potential of improving the quality of life for many thousands of people throughout the world. One particular area which presents an exciting challenge in this field is the repair and regeneration of cartilage where traumatic injuries and arthritis result in pain and restriction of movement. In order to achieve this goal of tissue engineering cartilage, there are three necessary components: cells for the generation of tissue, a scaffold to support growth and that degrades as the extracellular matrix is generated and a bioactive factor to stimulate the correct biological signals in vivo for tissue growth and integration with native cartilage. Over the last number of years there has been significant interest in progenitor stem cells for TE applications. Mesenchymal stem cells (MSCs) have been shown to differentiate into a range of tissues including bone, cartilage, muscle, tendon, skin and fat. Furthermore, a number of biocompatible biodegradable materi...
Signal Transduction and Targeted Therapy
Galway, Ireland Fibrin Microspheres Extend the Gene Delivery Capacity in a Fibrin Scaffold Manges... more Galway, Ireland Fibrin Microspheres Extend the Gene Delivery Capacity in a Fibrin Scaffold Mangesh M Kulkarni, Udo Greiser, Timothy O’Brien and Abhay Pandit Network of Excellence for Functional Biomaterials; Regenerative Medicine Institute; National University of Ireland, Galway, Ireland Abhay.pandit@nuigalway.ie Introduction The greatest challenge for non-viral vectors is the sustained release of a sufficient amount of a gene at the disease site to accomplish therapeutic benefit. Previously, we have shown that sustained delivery of two reporter genes (at a total dose of 5 μg pDNA) is feasible in a rabbit ear ulcer model up to 7 days via a fibrin scaffoldlipoplex system. The objective of this study was to enhance the capacity of the fibrin scaffold to carry higher amounts of DNA complexes. We have hypothesized that fibrin scaffold augmented by fibrin microspheres (FM) can be fabricated to encapsulate higher amounts of DNAcomplexes and that the DNA complexes remain intact and functio...
Quantification of eluted nucleic acids is critical in characterizing biomaterial based non-viral ... more Quantification of eluted nucleic acids is critical in characterizing biomaterial based non-viral gene-delivery systems. The standard quantification assay uses an intercalating fluorescent dye such as PicoGreen®. However, this technique was developed for unbound DNA and the current trend in gene delivery is to condense DNA with transfection reagents which interfere with intercalation. Here, DNA was permanently labeled with the fluorescent dye Cy5 prior to complexation in an alternative technique hypothesized to allow improved quantification of eluted DNA. The two methods were compared by quantifying the elution of six different varieties of DNA complexes from a collagen scaffold. After seven days of elution, PicoGreen® only allowed detection of three types of complexes while the fluorescent labeling technique detected all six varieties including poly(ethylene imine) and poly-L-Lysine complexes, allowing quantification of elution in all samples. Thus, the technique described in this study allows reliable quantification of DNA independent of complexation state.
INTRODUCTION and DISCUSSION: Textbook definitions of cartilage generally identify three classes o... more INTRODUCTION and DISCUSSION: Textbook definitions of cartilage generally identify three classes of histologically distinguishable cartilage: hyaline, fibroand elasticcartilage. However a survey of cartilage histology throughout vertebrate lineages illustrates that cartilage as a tissue type exhibits an entire spectrum of histological diversity. Indeed, the notochord remains ambiguous as to whether or not it can be considered a type of cartilage despite expression of various cartilage-specific markers (see below) and its persistence into adulthood in various lineages. In addition, examples of cellular cartilages are found in a number of invertebrate lineages, including arthropods, annelids, and molluscs. Although the existence of these tissues outside of the vertebrate lineages is known, the relationship between invertebrate and vertebrate cartilage is at best unclear. A strong vertebrate fossil record gives much information about the evolution of mineralized tissues, but has little ...
Biochemical Society Transactions
The extracellular matrix (ECM) dynamics in tumour tissue are deregulated compared to the ECM in h... more The extracellular matrix (ECM) dynamics in tumour tissue are deregulated compared to the ECM in healthy tissue along with disorganized architecture and irregular behaviour of the residing cells. Nitric oxide (NO) as a pleiotropic molecule exerts different effects on the components of the ECM driving or inhibiting augmented angiogenesis and tumour progression and tumour cell proliferation and metastasis. These effects rely on the concentration of NO within the tumour tissue, the nature of the surrounding microenvironment and the sensitivity of resident cells to NO. In this review article, we summarize the recent findings on the correlation between the levels of NO and the ECM components towards the modulation of tumour angiogenesis in different types of cancers. These are discussed principally in the context of how NO modulates the expression of ECM proteins resulting in either the promotion or inhibition of tumour growth via tumour angiogenesis. Furthermore, the regulatory effects o...
International Journal of Molecular Sciences
Mesenchymal stem cells (MSCs) can improve chronic wound healing; however, recent studies suggest ... more Mesenchymal stem cells (MSCs) can improve chronic wound healing; however, recent studies suggest that the therapeutic effect of MSCs is mediated mainly through the growth factors and cytokines secreted by these cells, referred to as the MSC secretome. To overcome difficulties related to the translation of cell therapy into clinical use such as efficacy, safety and cost, we propose a hydrogel loaded with a secretome from the recently established human adipose tissue mesenchymal stem cell line (HATMSC2) as a potential treatment for chronic wounds. Biocompatibility and biological activity of hydrogel-released HATMSC2 supernatant were investigated in vitro by assessing the proliferation and metabolic activity of human fibroblast, endothelial cells and keratinocytes. Hydrogel degradation was measured using hydroxyproline assay while protein released from the hydrogel was assessed by interleukin-8 (IL-8) and macrophage chemoattractant protein-1 (MCP-1) ELISAs. Pro-angiogenic activity of t...
Advanced Science
Abstract Chronic limb threatening ischemia (CLTI) is a severe condition defined by the blockage o... more Abstract Chronic limb threatening ischemia (CLTI) is a severe condition defined by the blockage of arteries in the lower extremities that leads to the degeneration of blood vessels and is characterized by the formation of non‐healing ulcers and necrosis. The gold standard therapies such as bypass and endovascular surgery aim at the removal of the blockage. These therapies are not suitable for the so‐called “no option patients” which present multiple artery occlusions with a likelihood of significant limb amputation. Therefore, CLTI represents a significant clinical challenge, and the efforts of developing new treatments have been focused on stimulating angiogenesis in the ischemic muscle. The delivery of pro‐angiogenic nucleic acid, protein, and stem cell‐based interventions have limited efficacy due to their short survival. Engineered biomaterials have emerged as a promising method to improve the effectiveness of these latter strategies. Several synthetic and natural biomaterials are tested in different formulations aiming to incorporate nucleic acid, proteins, stem cells, macrophages, or endothelial cells in supportive matrices. In this review, an overview of the biomaterials used alone and in combination with growth factors, nucleic acid, and cells in preclinical models is provided and their potential to induce revascularization and regeneration for CLTI applications is discussed.
ACS Nano
Cell membrane-coated (CMC) mimics are micro/nanosystems that combine an isolated cell membrane an... more Cell membrane-coated (CMC) mimics are micro/nanosystems that combine an isolated cell membrane and a template of choice to mimic the functions of a cell. The design exploits its physicochemical and biological properties for therapeutic applications. The mimics demonstrate excellent biological compatibility, enhanced biointerfacing capabilities, physical, chemical, and biological tunability, ability to retain cellular properties, immune escape, prolonged circulation time, and protect the encapsulated drug from degradation and active targeting. These properties and the ease of adapting them for personalized clinical medicine have generated a significant research interest over the past decade. This review presents a detailed overview of the recent advances in the development of cell membrane-coated (CMC) mimics. The primary focus is to collate and discuss components, fabrication methodologies, and the significance of physiochemical and biological characterization techniques for validating a CMC mimic. We present a critical analysis of the two main components of CMC mimics: the template and the cell membrane and mapped their use in therapeutic scenarios. In addition, we have emphasized on the challenges associated with CMC mimics in their clinical translation. Overall, this review is an up to date toolbox that researchers can benefit from while designing and characterizing CMC mimics.
Journal of Biomedical Materials Research Part B: Applied Biomaterials
Abstract Interstitial cystitis (IC) is a progressive bladder disease characterized by increased u... more Abstract Interstitial cystitis (IC) is a progressive bladder disease characterized by increased urothelial permeability, inflammation of the bladder with abdominal pain. While there is no consensus on the etiology of the disease, it was believed that restoring the barrier between urinary solutes and (GAG) urothelium would interrupt the progression of this disease. Currently, several treatment options include intravesical delivery of hyaluronic acid (HA) and/or chondroitin sulfate solutions, through a catheter to restore the urothelial barrier, but have shown limited success in preclinical, clinical trials. Herein we report for the first time successful engineering and characterization of biphasic system developed by combining cross‐linked hyaluronic acid and naïve HA solution to decrease inflammation and permeability in an in vitro model of interstitial cystitis. The cross‐linking of HA was performed by 4‐arm‐polyethyeleneamine chemistry. The HA formulations were tested for their viscoelastic properties and the effects on cell metabolism, inflammatory markers, and permeability. Our study demonstrates the therapeutic effects of different ratios of the biphasic system and reports their ability to increase the barrier effect by decreasing the permeability and alteration of cell metabolism with respect to relative controls. Restoring the barrier by using biphasic system of HA therapy may be a promising approach to IC.
Frontiers in Bioengineering and Biotechnology
The potential biomedical applications of nanodiamond have been considered over the last few decad... more The potential biomedical applications of nanodiamond have been considered over the last few decades. However, there is still uncertainty regarding the extent to which the surface characteristics of this material can influence potential applications. The present study investigated the effects of surface characteristics alongside the prospective of improving nanodiamond production using cold plasma and microwave technologies for the surface tailoring of the nanocarbons. Numerous approaches were applied to purify, refine and modify a group of nanosized diamonds at each step of their production cycle: from the detonation soot as the initial raw material to already certified samples. The degree of surface changes were deliberately performed slowly and kept at different non-diamond carbon presence stages, non-carbon elemental content, and amount converted superficial moieties. In total, 21 treatment procedures and 35 types of nanosize diamond products were investigated. In addition cultur...
Journal of Neuroinflammation
Background Neuroinflammation is an underlying pathology of all neurological conditions, the under... more Background Neuroinflammation is an underlying pathology of all neurological conditions, the understanding of which is still being comprehended. A specific molecular pathway that has been overlooked in neuroinflammation is glycosylation (i.e., post-translational addition of glycans to the protein structure). N-glycosylation is a specific type of glycosylation with a cardinal role in the central nervous system (CNS), which is highlighted by congenital glycosylation diseases that result in neuropathological symptoms such as epilepsy and mental retardation. Changes in N-glycosylation can ultimately affect glycoproteins’ functions, which will have an impact on cell machinery. Therefore, characterisation of N-glycosylation alterations in a neuroinflammatory scenario can provide a potential target for future therapies. Methods With that aim, the unilateral intrastriatal injection of lipopolysaccharide (LPS) in the adult rat brain was used as a model of neuroinflammation. In vivo and post-m...
JOR SPINE
Spine‐related infections, such as vertebral osteomyelitis, discitis, or spondylitis, are rare dis... more Spine‐related infections, such as vertebral osteomyelitis, discitis, or spondylitis, are rare diseases that mostly affect adults, and are usually of hematogenous origin. The incidence of this condition has gradually risen in recent years because of increases in spine‐related surgery and hospital‐acquired infections, an aging population, and intravenous (IV) drug use. Spine infections are most commonly caused by Staphylococcus aureus, while other systemic infections such as tuberculosis and brucellosis can also cause spondylitis. Various animal models of vertebral osteomyelitis and associated infections have been investigated in mouse, rat, chicken, rabbit, dog, and sheep models by hematogenous and direct inoculation in surgery, each with their strengths and limitations. This review is the first of its kind to concisely analyze the various existing animal models used to reproduce clinically relevant models of infection. Spine‐related infection models must address the unique anatomy of the spine, the avascular nature of its structures and tissues and the consequences of tissue destruction such as spinal cord compression. Further investigation is necessary to elucidate the specific mechanisms of host‐microbe response to inform antimicrobial therapy and administration techniques in a technically demanding body cavity. Small‐animal models are not suitable for large instrumentation, and difficult IV access thwarts antibiotic administration. In contrast, large‐animal models can be implanted with clinically relevant instrumentation and are resilient to repeat procedures to study postoperative infection. A canine model of infection offers a unique opportunity to design and investigate antimicrobial treatments through recruitment a rich population of canine patients, presenting with a natural disease that is suitable for randomized trials.
Advanced Healthcare Materials
Academic institutions are becoming more focused on translating new technologies for clinical appl... more Academic institutions are becoming more focused on translating new technologies for clinical applications. A transition from "bench to bedside" is often described to take basic research concepts and methods to develop a therapeutic or diagnostic solution with proven evidence of efficacy at the clinical level while also fulfilling regulatory requirements. The regulatory environment is evolving in Europe with transition and grace periods for the full enforcement of the Medical Device Regulation 2017/745 (MDR), replacing the Medical Device Directive 93/42/EEC (MDD). These new guidelines increase demands for scientific, technical, and clinical data with reduced capacity in regulatory bodies creating uncertainty in future product certification. Academic translational activities will be uniquely affected by this new legislation. The barriers and threats to successful translation in academia can be overcome by strong clinical partnerships, close-industrial collaborations, and entrepreneurial programs, enabling continued product development to overcome regulatory hurdles, reassuring their foothold of medical device development.
European Cells and Materials
Intervertebral disc (IVD) degeneration causes low-back pain through disc compression, prolapse an... more Intervertebral disc (IVD) degeneration causes low-back pain through disc compression, prolapse and herniation. Inflammation of the IVD and subsequent degeneration produce altered glycosylation profiles in several animal models of IVD injury and ageing, although the function of this altered glycosylation pattern in a human is unknown. Altered N-glycome, specifically sialylated and fucosylated N-glycosylation motif expression, might play a role in inflammation and disease progression. Healthy (foetal and adolescent idiopathic scoliosis) and degenerated (lumbar degeneration) human IVD glycosylation patterns were studied using lectin histochemistry. Small-molecule fluorinated sugar analogues (3Fax-Peracetyl Neu5Ac; 2F-Peracetyl-Fucose) were used to inhibit sialylation and fucosylation in an in vitro model of inflammation, to investigate their effects on the glycosignature, cell metabolism, extracellular matrix synthesis and cell migration. The effects of interleukin (IL)-1β, tumour necr...
Tendon injuries represent a significant clinical burden on healthcare systems worldwide. As the h... more Tendon injuries represent a significant clinical burden on healthcare systems worldwide. As the human population ages and the life expectancy increases, tendon injuries will become more prevalent, especially among young individuals with long life ahead of them. Advancements in engineering, chemistry and biology have made available an array of three-dimensional scaffold-based intervention strategies, natural or synthetic in origin. Further, functionalisation strategies, based on biophysical, biochemical and biological cues, offer control over cellular functions; localisation and sustained release of therapeutics/biologics; and the ability to positively interact with the host to promote repair and regeneration. Herein, we critically discuss current therapies and emerging technologies that aim to transform tendon treatments in the years to come.