CÚRAM - Centre for Research in Medical Devices (Scholarly Articles)

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  • Publication
    Characterization of the ‘White’ appearing clots that cause acute ischemic stroke
    (Elsevier, 2021-09-28) Mereuta, Oana Madalina; Rossi, Rosanna; Douglas, Andrew; Molina Gil, Sara; Fitzgerald, Seán; Pandit, Abhay; McCarthy, Ray; Gilvarry, Michael; Ceder, Eric; Dunker, Dennis; Nordanstig, Annika; Redfors, Petra; Jood, Katarina; Magoufis, Georgios; Psychogios, Klearchos; Tsivgoulis, Georgios; O'Hare, Alan; Power, Sarah; Brennan, Paul; Nagy, András; Vadász, Ágnes; Brinjikji, Waleed; Kallmes, David F.; Szikora, Istvan; Rentzos, Alexandros; Tatlisumak, Turgut; Thornton, John; Doyle, Karen M.; Science Foundation Ireland; European Regional Development Fund; National Institutes of Health
    Objectives Most clots retrieved from patients with acute ischemic stroke are ‘red’ in color. ‘White’ clots represent a less common entity and their histological composition is less known. Our aim was to investigate the composition, imaging and procedural characteristics of ‘white’ clots retrieved by mechanical thrombectomy. Materials and methods Seventy five ‘white’ thrombi were selected by visual inspection from a cohort of 760 clots collected as part of the RESTORE registry. Clots were evaluated histopathologically. Results Quantification of Martius Scarlett Blue stain identified platelets/other as the major component in ‘white’ clots’ (mean of 55% of clot overall composition) followed by fibrin (31%), red blood cells (6%) and white blood cells (3%). ‘White’ clots contained significantly more platelets/other (p<0.001*) and collagen/calcification (p<0.001*) and less red blood cells (p<0.001*) and white blood cells (p=0.018*) than ‘red’ clots. The mean platelet and von Willebrand Factor expression was 43% and 24%, respectively. Adipocytes were found in four cases. ‘White’ clots were significantly smaller (p=0.016*), less hyperdense (p=0.005*) on computed tomography angiography/non-contrast CT and were associated with a smaller extracted clot area (p<0.001*) than ‘red’ clots. They primarily caused the occlusion of middle cerebral artery, were less likely to be removed by aspiration and more likely to require rescue-therapy for retrieval. Conclusions ‘White’ clots represented 14% of our cohort and were platelet, von Willebrand Factor and collagen/calcification-rich. ‘White’ clots were smaller, less hyperdense, were associated with significantly more distal occlusions and were less successfully removed by aspiration alone than ‘red’ clots.
  • Publication
    Histological evaluation of acute ischemic stroke thrombi may indicate the occurrence of vessel wall injury during mechanical thrombectomy
    (BMJ Publishing Group, 2021-05-11) Mereuta, Oana Madalina; Doyle, Karen M.
    Background Several animal studies have demonstrated that mechanical thrombectomy (MT) for acute ischemic stroke (AIS) may cause vessel wall injury (VWI). However, the histological changes in human cerebral arteries following MT are difficult to determine. Objective To investigate the occurrence of VWI during MT by histological and immunohistochemical evaluation of AIS clots. Methods As part of the multicenter STRIP registry, 277 clots from 237 patients were analyzed using Martius Scarlett Blue stain and immunohistochemistry for CD34 (endothelial cells) and smooth muscle actin (smooth muscle cells). Results MT devices used were aspiration catheters (100 cases), stentriever (101 cases), and both (36 cases). VWI was found in 33/277 clots (12%). There was no significant correlation between VWI and MT device. The degree of damage varied from grade I (mild intimal damage, 24 clots), to grade II (relevant intimal and subintimal damage, 3 clots), and III (severe injury, 6 clots). VWI clots contained significantly more erythrocytes (p=0.006*) and less platelets/other (p=0.005*) than non-VWI clots suggesting soft thrombus material. Thrombolysis correlated with a lower rate of VWI (p=0.04*). VWI cases showed a significantly higher number of passes (2 [1–4] vs 1 [1–3], p=0.028*) and poorer recanalization outcome (p=0.01*) than cases without VWI. Conclusions Histological markers of VWI were present in 12% of AIS thrombi, suggesting that VWI might be related to MT. VWI was associated with soft thrombus consistency, higher number of passes and poorer revascularization outcome. There was no significant correlation between VWI and MT device.
  • Publication
    Bioactive potential of natural biomaterials: identification, retention and assessment of biological properties
    (Springer Nature, 2021-03-19) Joyce, Kieran; Fabra, Georgina Targa; Bozkurt, Yagmur; Pandit, Abhay; Science Foundation Ireland; European Regional Development Fund; College of Medicine, Nursing and Health Sciences, National University of Ireland Galway; Horizon 2020
    Biomaterials have had an increasingly important role in recent decades, in biomedical device design and the development of tissue engineering solutions for cell delivery, drug delivery, device integration, tissue replacement, and more. There is an increasing trend in tissue engineering to use natural substrates, such as macromolecules native to plants and animals to improve the biocompatibility and biodegradability of delivered materials. At the same time, these materials have favourable mechanical properties and often considered to be biologically inert. More importantly, these macromolecules possess innate functions and properties due to their unique chemical composition and structure, which increase their bioactivity and therapeutic potential in a wide range of applications. While much focus has been on integrating these materials into these devices via a spectrum of cross-linking mechanisms, little attention is drawn to residual bioactivity that is often hampered during isolation, purification, and production processes. Herein, we discuss methods of initial material characterisation to determine innate bioactivity, means of material processing including cross-linking, decellularisation, and purification techniques and finally, a biological assessment of retained bioactivity of a final product. This review aims to address considerations for biomaterials design from natural polymers, through the optimisation and preservation of bioactive components that maximise the inherent bioactive potency of the substrate to promote tissue regeneration.
  • Publication
    High-resolution scanning electron microscopy for the analysis of three-dimensional ultrastructure of clots in acute ischemic stroke
    (BMJ Publishing Group, 2020-12-23) Mereuta, Oana Madalina; Fitzgerald, Seán; Christensen, Trace A.; Jaspersen, Adam L.; Dai, Daying; Abbasi, Mehdi; Puttappa, Tejaswini; Kadirvel, Ram; Kallmes, David F.; Doyle, Karen M.; Brinjikji, Waleed; National Institutes of Health; Science Foundation Ireland; European Regional Development Fund
    Background: Characterization of acute ischemic stroke (AIS) clots has typically focused on two dimensional histological analysis of the thrombus. The three dimensional (3D) architecture and distribution of components within emboli have not been fully investigated. The aim of this study was to examine the composition and microstructure of AIS clots using histology and serial block-face scanning electron microscopy (SBFSEM). Methods: As part of the multi-institutional STRIP registry, ten consecutive AIS emboli were collected from ten patients treated by mechanical thrombectomy. Histological and immunohistochemical analysis was performed to determine clot composition. SBFSEM was used to assess ultrastructural organization of clots and specific features of individual components. Results: Quantification of Martius Scarlett Blue stain identified fibrin (44.4%) and red blood cells (RBC, 32.6%) as main components. Immunohistochemistry showed a mean platelet and von Willebrand content of 23.9% and 11.8%, respectively. The 3D organization of emboli varied greatly depending on the region analyzed. RBC-rich areas were composed of tightly packed RBC deformed into polyhedrocytes with scant fibrin fibers interwoven between cells. Regions with mixed composition showed thick fibrin fibers along with platelets, white blood cells and RBC clusters. Fibrin-rich areas contained dense fibrin masses with sparse RBC. In three cases, the fibrin formed a grid-like or a sponge-like pattern likely due to thrombolytic treatment. Segmentation showed that fibrin fibers were thinner and less densely packed in these cases. Conclusions: 3D-SEM provides novel and potentially clinically relevant information on clot components and ultrastructure which may help to inform thrombolytic treatment and medical device design.
  • Publication
    Automation, monitoring, and standardization of cell product manufacturing
    (Frontiers Media, 2020-07-14) Doulgkeroglou, Meletios-Nikolaos; Di Nubila, Alessia; Niessing, Bastian; König, Niels; Schmitt, Robert H.; Damen, Jackie; Szilvassy, Stephen J.; Chang, Wing; Csontos, Lynn; Louis, Sharon; Kugelmeier, Patrick; Ronfard, Vincent; Bayon, Yves; Zeugolis, Dimitrios I.; Science Foundation Ireland; European Regional Development Fund
    Although regenerative medicine products are at the forefront of scientific research, technological innovation, and clinical translation, their reproducibility and large-scale production are compromised by automation, monitoring, and standardization issues. To overcome these limitations, new technologies at software (e.g., algorithms and artificial intelligence models, combined with imaging software and machine learning techniques) and hardware (e.g., automated liquid handling, automated cell expansion bioreactor systems, automated colony-forming unit counting and characterization units, and scalable cell culture plates) level are under intense investigation. Automation, monitoring and standardization should be considered at the early stages of the developmental cycle of cell products to deliver more robust and effective therapies and treatment plans to the bedside, reducing healthcare expenditure and improving services and patient care.
  • Publication
    Electric field stimulation for tissue engineering applications
    (BMC (part of Springer Nature), 2021-01-05) Ryan, Christina N. M.; Doulgkeroglou, Meletios N.; Zeugolis, Dimitrios I.; Science Foundation Ireland; European Regional Development Fund; European Research Council; Horizon 2020
    Electric fields are involved in numerous physiological processes, including directional embryonic development and wound healing following injury. To study these processes in vitro and/or to harness electric field stimulation as a biophysical environmental cue for organised tissue engineering strategies various electric field stimulation systems have been developed. These systems are overall similar in design and have been shown to influence morphology, orientation, migration and phenotype of several different cell types. This review discusses different electric field stimulation setups and their effect on cell response.
  • Publication
    A glycotherapeutic approach to functionalize biomaterials-based systems
    (Wiley, 2020-03-18) Gadekar, Anuja; Bhowmick, Sirsendu; Pandit, Abhay; Science Foundation Ireland; European Regional Development Fund; Horizon 2020
    In addition to being one of the primary building block materials of living cells, glycans are also favorable candidates for therapeutic applications. In the mid-20th century, the progress of glycans in the drug discovery field became surpassed by protein and DNA-focused treatments. However, the emergence of new analytical tools and methods to synthesize structurally specific glycans has encouraged and motivated the scientific community toward the development of glycan-based therapeutics. This review discusses the reemergence of glycan-based agents in the last decade and the technical strategies that played a key role in bringing the glycan-based treatments into the limelight of modern medicine. The review also includes the application of native glycans as the therapeutic agents along with the chemically engineered cell surface glycans and proteins to meet the preclinical and clinical scenario. Glycan-based therapeutic materials hold a huge potential that can be harnessed to meet the clinical needs in medicine.
  • Publication
    Design and characterization of synthetic biodegradable films for soft tissue engineering
    (SciTePress, 2019) Ribeiro, Sofia; Fernandes, Emanuel; Gomes, Manuela; Reis, Rui; Bayon, Yves; Zeugolis, Dimitrios I.; Horizon 2020
    To repair soft tissue, it is vital to ensure that the biomaterial is able to mimic the complex elasticity of the native tissue. Substrate stiffness has a huge influence on cell physiology and behaviour. The present study presents a set of polymeric films as initial support matrix of cells. A range of synthetic biodegradable polymers was selected according to the physico-chemical intrinsic properties of aliphatic polymers. They have similar chemistry (absorbable polyesters made from lactic acid, glycolic acid, trimethylene carbonate, dioxanone & β-caprolactone), however show different mechanical and degradation properties. The films were manufactured by thermal presser and then characterized by scanning electron microscopy, differential scanning calorimetry, nuclear magnetic resonance spectroscopy and Fourier transform infrared spectroscopy. The mechanical properties of the films were assessed by uniaxial tensile tests in wet conditions and also by atomic force microscopy. In vitro as says were performed to assess the cell cytocompatibility, proliferation and differentiation potential of the films. The mechanical properties of the materials are within the range intended for musculoskeletal tissue repair. Biological assays showed good cell adhesion, cell proliferation and cell viability. In the future, the combined effect of stiffness and topography will be assessed on cell phenotype maintenance.
  • Publication
    Current and upcoming therapies to modulate skin scarring and fibrosis
    (Elsevier, 2018-08-30) Coentro, João Q.; Pugliese, Eugenia; Hanley, Geoffrey; Raghunath, Michael; Zeugolis, Dimitrios I.; Health Research Board; Science Foundation Ireland; Horizon 2020; European Regional Development Fund
    Skin is the largest organ of the human body. Being the interface between the body and the outer environment, makes it susceptible to physical injury. To maintain life, nature has endowed skin with a fast healing response that invariably ends in the formation of scar at the wounded dermal area. In many cases, skin remodelling may be impaired, leading to local hypertrophic scars or keloids. One should also consider that the scarring process is part of the wound healing response, which always starts with inflammation. Thus, scarring can also be induced in the dermis, in the absence of an actual wound, during chronic inflammatory processes. Considering the significant portion of the population that is subject to abnormal scarring, this review critically discusses the state-of-the-art and upcoming therapies in skin scarring and fibrosis.
  • Publication
    The synergistic effect of low oxygen tension and macromolecular crowding in the development of extracellular matrix-rich tendon equivalents
    (IOP Publishing, 2020-02-26) Tsiapalis, Dimitrios; De Pieri, Andrea; Spanoudes, Kyriakos; Sallent, Ignacio; Kearns, Stephen; Kelly, Jack L.; Raghunath, Michael; Zeugolis, Dimitrios I.; Horizon 2020; Science Foundation Ireland; European Regional Development Fund
    Cellular therapies play an important role in tendon tissue engineering, with tenocytes being the most prominent and potent cell population available. However, for the development of a rich extracellular matrix tenocyte-assembled tendon equivalent, prolonged in vitro culture is required, which is associated with phenotypic drift. Recapitulation of tendon tissue microenvironment in vitro with cues that enhance and accelerate extracellular matrix synthesis and deposition, whilst maintaining tenocyte phenotype, may lead to functional cell therapies. Herein, we assessed the synergistic effect of low oxygen tension (enhances extracellular matrix synthesis) and macromolecular crowding (enhances extracellular matrix deposition) in human tenocyte culture. Protein analysis demonstrated that human tenocytes at 2% oxygen tension and with 50 μg ml−1 carrageenan (macromolecular crowder used) significantly increased synthesis and deposition of collagen types I, III, V and VI. Gene analysis at day 7 illustrated that human tenocytes at 2% oxygen tension and with 50 μg ml−1 carrageenan significantly increased the expression of prolyl 4-hydroxylase subunit alpha 1, procollagen-lysine 2- oxoglutarate 5-dioxygenase 2, scleraxis, tenomodulin and elastin, whilst chondrogenic (e.g. runt-related transcription factor 2, cartilage oligomeric matrix protein, aggrecan) and osteogenic (e.g. secreted phosphoprotein 1, bone gamma-carboxyglutamate protein) trans-differentiation markers were significantly down-regulated or remained unchanged. Collectively, our data clearly illustrates the beneficial synergistic effect of low oxygen tension and macromolecular crowding in the accelerated development of tissue equivalents.
  • Publication
    Preparation and characterization of tissue surrogates rich in extracellular matrix using the principles of macromolecular crowding
    (Humana Press, 2019-03) Djalali-Cuevas, Adrian; Garnica-Galvez, Sergio; Rampin, Andrea; Gaspar, Diana; Skoufos, Ioannis; Tzora, Athina; Prassinos, Nikitas; Diakakis, Nikolaos; Zeugolis, Dimitrios I.; Horizon 2020; Science Foundation Ireland; European Regional Development Fund
    Tissue engineering by self-assembly allows for the fabrication of living tissue surrogates by taking advantage of the cell's inherent ability to produce and deposit tissue-specific extracellular matrix. However, the long culture periods required to build a tissue substitute in conducive to phenotypic drift in vitro microenvironments result in phenotype and function losses. Although several biophysical microenvironmental modulators (e.g., surface topography, substrate stiffness, mechanical stimulation) have been used to address these issues, slow extracellular matrix deposition remains a limiting factor in clinical translation and commercialization of such therapies. Macromolecular crowding is an alternative in vitro microenvironment modulator that has been shown to accelerate extracellular matrix deposition by several orders of magnitude, thereby decreasing culture periods required for the development of an implantable device, while maintaining cell phenotype and function. Herein, we provide protocols for the production of tissue surrogates rich in extracellular matrix from human dermal fibroblasts, equine tenocytes, and equine adipose-derived stem cells using the principles of macromolecular crowding and the subsequent characterization thereof by means of immunofluorescent staining and complementary fluorescence intensity analysis.
  • Publication
    The collagen suprafamily: From biosynthesis to advanced biomaterial development
    (Wiley, 2018-08-20) Sorushanova, Anna; Delgado, Luis M.; Wu, Zhuning; Shologu, Naledi; Kshirsagar, Aniket; Raghunath, Rufus; Mullen, Anne M.; Bayon, Yves; Pandit, Abhay; Raghunath, Michael; Zeugolis, Dimitrios I.; Teagasc Walsh Fellowship; Department of Agriculture, Food and the Marine, Ireland; Health Research Board; Science Foundation Ireland; European Regional Development Fund; College of Engineering and Informatics, National University of Ireland, Galway; Seventh Framework Programme; Horizon 2020
    Collagen is the oldest and most abundant extracellular matrix protein that has found many applications in food, cosmetic, pharmaceutical, and biomedical industries. First, an overview of the family of collagens and their respective structures, conformation, and biosynthesis is provided. The advances and shortfalls of various collagen preparations (e.g., mammalian/marine extracted collagen, cell-produced collagens, recombinant collagens, and collagen-like peptides) and crosslinking technologies (e.g., chemical, physical, and biological) are then critically discussed. Subsequently, an array of structural, thermal, mechanical, biochemical, and biological assays is examined, which are developed to analyze and characterize collagenous structures. Lastly, a comprehensive review is provided on how advances in engineering, chemistry, and biology have enabled the development of bioactive, 3D structures (e.g., tissue grafts, biomaterials, cell-assembled tissue equivalents) that closely imitate native supramolecular assemblies and have the capacity to deliver in a localized and sustained manner viable cell populations and/or bioactive/therapeutic molecules. Clearly, collagens have a long history in both evolution and biotechnology and continue to offer both challenges and exciting opportunities in regenerative medicine as nature's biomaterial of choice.
  • Publication
    Hypoxia preconditioning of bone marrow mesenchymal stem cells before implantation in orthopaedics
    (Lippincott, Williams & Wilkins, 2019-12-01) Tsiapalis, Dimitrios; Zeugolis, Dimitrios I.; Horizon 2020; Science Foundation Ireland; European Regional Development Fund
    [No abstract available]
  • Publication
    Local pharmacological induction of angiogenesis: drugs for cells and cells as drugs
    (Elsevier, 2019-06-19) Gaspar, Diana; Peixoto, Rita; De Pieri, Andrea; Striegl, Britta; Zeugolis, Dimitrios I.; Raghunath, Michael; Science Foundation Ireland; Horizon 2020
    The past decades have seen significant advances in pro-angiogenic strategies based on delivery of molecules and cells for conditions such as coronary artery disease, critical limb ischemia and stroke. Currently, three major strategies are evolving. Firstly, various pharmacological agents (growth factors, interleukins, small molecules, DNA/RNA) are locally applied at the ischemic region. Secondly, preparations of living cells with considerable bandwidth of tissue origin, differentiation state and preconditioning are delivered locally, rarely systemically. Thirdly, based on the notion, that cellular effects can be attributed mostly to factors secreted in situ, the cellular secretome (conditioned media, exosomes) has come into the spotlight. We review these three strategies to achieve (neo)angiogenesis in ischemic tissue with focus on the angiogenic mechanisms they tackle, such as transcription cascades, specific signalling steps and cellular gases. We also include cancer-therapy relevant lymphangiogenesis, and shall seek to explain why there are often conflicting data between in vitro and in vivo. The lion's share of data encompassing all three approaches comes from experimental animal work and we shall highlight common technical obstacles in the delivery of therapeutic molecules, cells, and secretome. This plethora of preclinical data contrasts with a dearth of clinical studies. A lack of adequate delivery vehicles and standardised assessment of clinical outcomes might play a role here, as well as regulatory, IP, and manufacturing constraints of candidate compounds; in addition, completed clinical trials have yet to reveal a successful and efficacious strategy. As the biology of angiogenesis is understood well enough for clinical purposes, it will be a matter of time to achieve success for well-stratified patients, and most probably with a combination of compounds.
  • Publication
    Joint academic and industrial efforts towards innovative and efficient solutions for clinical needs
    (Springer Verlag, 2018-07-31) De Pieri, Andrea; Ribeiro, Sofia; Tsiapalis, Dimitrios; Eglin, David; Bohner, Marc; Dubruel, Peter; Proctor, Philip; Zeugolis, Dimitrios I.; Bayon, Yves; Horizon 2020; Science Foundation Ireland
    The 4th Translational Research Symposium (TRS) was organised at the annual meeting of the European Society for Biomaterials (ESB) 2017, Athens, Greece, with a focus on ‘Academia—Industry Clusters of Research for Innovation Catalysis’. Collaborations between research institutes and industry can be sustained in several ways such as: European Union (EU) funded consortiums; syndicates of academic institutes, clinicians and industries; funding from national governments; and private collaborations between universities and companies. Invited speakers from industry and research institutions presented examples of these collaborations in the translation of research ideas or concepts into marketable products. The aim of the present article is to summarize the key messages conveyed during these lectures. In particular, emphasis is put on the challenges to appropriately identify and select unmet clinical needs and their translation by ultimately implementing innovative and efficient solutions achieved through joint academic and industrial efforts.
  • Publication
    Low resistance, highly corrugated structures based on poly(3,4-ethylenedioxythiophene) doped with a d-glucopyranoside-derived ionic liquid
    (Elsevier, 2019-12-02) Krukiewicz, Katarzyna; Kobus, Dominika; Turczyn, Roman; Erfurt, Karol; Chrobok, Anna; Biggs, Manus J. P.; Science Foundation Ireland; European Regional Development Fund; Horizon 2020
    Conjugated polymers have gained significant interest as highly conducting organic materials with versatile surface morphology. In this study, we demonstrate that the electrodeposition of poly(3,4-ethylenedioxythiophene), PEDOT, in the presence of a d-glucopyranoside-derived ionic liquid (IL) results in the formation of highly corrugated three-dimensional structures. The as-formed PEDOT/IL is found to outperform PEDOT electrodeposited in the presence of a conventional electrolyte (KCl) in terms of the low impedance at the biologically relevant frequency (1 kHz) and low charge transfer resistance. Consequently, it can be inferred that the unique surface morphology and beneficial electrochemical performance will facilitate the application of PEDOT/IL in biomedical engineering, especially in the field of neural interfaces and tissue scaffolds.
  • Publication
    In vitro attenuation of astrocyte activation and neuroinflammation through ibuprofen-doping of poly(3,4-ethylenedioxypyrrole) formulations
    (Elsevier, 2020-04-08) Krukiewicz, Katarzyna; Kowalik, Agnieszka; Turczyn, Roman; Biggs, Manus J. P.; Science Foundation Ireland; European Regional Development Fund; Horizon 2020
    Neuroinflammation is often associated with poor functional recovery and may contribute to or initiate the development of severe neurological disorders, such as epilepsy, Parkinson's disease or Alzheimer's disease. Ibuprofen (IBU), being one of the most commonly used non-steroidal anti-inflammatory drugs, is known to possess neuroprotective activity and serve as a promising therapeutic for the treatment of neuroinflammation. In this study, the potential of an IBU-loaded poly(3,4-ethylenedioxypyrrole) (PEDOP) matrix has been assessed as a neural interface material with an aim to control astrocyte activation and suppress neuroinflammation in vitro. Three types of drug immobilization protocols were investigated, leading to the fabrication of IBU-loaded PEDOP matrices exhibiting a broad spectrum of electrical characteristics, drug release profiles, as well as biological responses. Among all investigated PEDOP formulations, PEDOP matrices formed through a three-step immobilization protocol exhibited the highest charge storage capacity (30 ± 1 mC/cm2) as well as a double layer capacitance of 645.0 ± 51.1 µF, associated with a relatively enlarged surface area. Demonstrating a total drug loading capacity of 150 µg/ml and a release rate constant of 0.15 1/h, this coating formulation may be employed as a safe electrical conducting drug eluting system.
  • Publication
    Biophysics rules the cell culture but has yet to reach the clinic: Why is that?
    (Lippincott, Williams & Wilkins, 2017-07) Guillaumin, Salomé; Sallent, Ignacio; Zeugolis, Dimitrios I.; Horizon 2020; Health Research Board; Science Foundation Ireland; European Regional Development Fund
    Musculoskeletal injuries are the leading cause of physical disability worldwide, with associated annual direct and indirect healthcare expenditure in excess of $874 billion in the United States alone.1 Current treatments are predominantly based on tissue grafts (autografts are preferred)2,3 and biomaterials.4,5 Given that the former are associated with scarce availability, insufficient remodeling, and adverse immune reactions,6-8 and the latter with substandard stability, poor biologic response, and foreign body response,9-11 their clinical suitability has been questioned and gave rise to the field of cell-based therapies.12
  • Publication
    Translational Research Symposium—collaborative efforts as driving forces of healthcare innovation
    (Springer Verlag, 2019-12-02) Coentro, João Q.; De Pieri, Andrea; Gaspar, Diana; Tsiapalis, Dimitrios; Zeugolis, Dimitrios I.; Bayon, Yves; Horizon 2020; Science Foundation Ireland
    The 5th Translational Research Symposium was organised at the annual meeting of the European Society for Biomaterials 2018, Maastricht, the Netherlands, with emphasis on the future of emerging and smart technologies for healthcare in Europe. Invited speakers from academia and industry highlighted the vision and expectations of healthcare in Europe beyond 2020 and the perspectives of innovation stakeholders, such as small and medium enterprises, large companies and Universities. The aim of the present article is to summarise and explain the main statements made during the symposium, with particular attention on the need to identify unmet clinical needs and their efficient translation into healthcare solutions through active collaborations between all the participants involved in the value chain.
  • Publication
    Therapeutic potential of intranasal photobiomodulation therapy for neurological and neuropsychiatric disorders: a narrative review.
    (De Gruyter, 2019-12-09) Salehpour, Farzad; Gholipour-Khalili, Sevda; Farajdokht, Fereshteh; Kamari, Farzin; Walski, Tomasz; Hamblin, Michael R.; DiDuro, Joseph O.; Cassano, Paolo; Horizon 2020; Science Foundation Ireland; European Regional Development Fund
    The application of photobiomodulation therapy (PBMT) for neuronal stimulation is studied in different animal models and in humans, and has shown to improve cerebral metabolic activity and blood flow, and provide neuroprotection via anti-inflammatory and antioxidant pathways. Recently, intranasal PBMT (i-PBMT) has become an attractive and potential method for the treatment of brain conditions. Herein, we provide a summary of different intranasal light delivery approaches including a nostril-based portable method and implanted deep-nasal methods for the effective systemic or direct irradiation of the brain. Nostril-based i-PBMT devices are available, using either lasers or light emitting diodes (LEDs), and can be applied either alone or in combination to transcranial devices (the latter applied directly to the scalp) to treat a wide range of brain conditions such as mild cognitive impairment, Alzheimer's disease, Parkinson's disease, cerebrovascular diseases, depression and anxiety as well as insomnia. Evidence shows that nostril-based i-PBMT improves blood rheology and cerebral blood flow, so that, without needing to puncture blood vessels, i-PBMT may have equivalent results to a peripheral intravenous laser irradiation procedure. Up to now, no studies were conducted to implant PBMT light sources deep within the nose in a clinical setting, but simulation studies suggest that deep-nasal PBMT via cribriform plate and sphenoid sinus might be an effective method to deliver light to the ventromedial part of the prefrontal and orbitofrontal cortex. Home-based i-PBMT, using inexpensive LED applicators, has potential as a novel approach for neurorehabilitation; comparative studies also testing sham, and transcranial PBMT are warranted.