336 research outputs found
Retinal Inflammaging: Pathogenesis and Prevention
Macula lutea, the yellow sot or fovea centralis in eye serves the distinctive central vision in perceiving visual cues and contributing to task performance. Impaired visual acuity in later years in life, compromises safety, productivity and life quality. Carotenoid pigment content declines with cumulation of light induced damage through aging process in retina. The progression of resultant macular degeneration is aggravated by oxidative stress, inflammation, raised blood sugar and vasculopathy associating aging. Senescent dry degeneration involves drusen (a compound of glycolipid and glycol-conjugate core) deposition that impairs metabolic connectivity of upper layers of retina with choroid. Degeneration of retinal pigment epithelium (RPE) and photoreceptors thus, results. The late more severe form of age related macular degeneration (AMD), involves factors inducing choroidal neo-vascularization. Leaky neo-capillaries speed degenerative process of retina. Most age related pathologies are initiated by metabolic disruptions and AMD shares features of systemic atherosclerosis. An aberrant tissue response to free radical stress, vasculopathy and local ischaemic underlies AMD pathogenesis.There is no specific treatment modality and prudent strategy in prophylaxis only. Early diagnosis and proper control of environmental and lifestyle factors are strived by newer biomedical understanding, which is briefly reviewed
Region-Specific Characterization of N-Glycans in the Striatum and Substantia Nigra of an Adult Rodent Brain
N-glycan alterations in the nervous system can result in different neuropathological symptoms such as mental retardation, seizures, and epilepsy. Studies have reported the characterization of N-glycans in rodent brains, but there is a lack of spatial resolution as either the tissue samples were homogenized or specific proteins were selected for analysis of glycosylation. We hypothesize that region-specific resolution of N-glycans isolated from the striatum and substantia nigra (SN) can give an insight into the establishment and pathophysiological degeneration of neural circuitry in Parkinson’s disease. Specific objectives of the study include isolation of N-glycans from the rat striatum and SN; reproducibility, resolution, and relative quantitation of N-glycome using ultra-performance liquid chromatography (UPLC), weak anion exchange-UPLC, and lectin histochemistry. The total N-glycomes from the striatum and SN were characterized using database mining (GlycoStore), exoglycosidase digestions, and liquid chromatography-mass spectrometry. It revealed significant differences in complex and oligomannose type N-glycans, sialylation (mono-, di-, and tetra-), fucosylation (tri-, core, and outer arm), and galactosylation (di-, tri-, and tetra-) between striatum and SN N-glycans with the detection of phosphorylated N-glycans in SN which were not detected in the striatum. This study presents the most comprehensive comparative analysis of relative abundances of N-glycans in the striatum and SN of rodent brains, serving as a foundation for identifying “brain-type” glycans as biomarkers or therapeutic targets and their modulation in neurodegenerative disorders
Cross-linked cholecyst-derived extracellular matrix for abdominal wall repair
Abdominal wall repair frequently utilizes either non-degradable or bio-degradable meshes,
which are found to stimulate undesirable biological tissue responses or which possess
suboptimal degradation rate. In this study, a biologic mesh prototype made from
carbodiimide-cross-linked cholecyst-derived extracellular matrix (EDCxCEM) was compared
with small intestinal submucosa (Surgisis®), cross-linked bovine pericardium (Peri-Guard®),
and polypropylene (Prolene®) meshes in an in vivo rabbit model. The macroscopic
appearance and stereological parameters of the meshes were evaluated. Tailoring the
degradation of the EDCxCEM mesh prevents untimely degradation, while allowing cellular
infiltration and mesh remodelling to take place in a slower but predictable manner. The
results suggest that the cross-linked biodegradable cholecyst-derived biologic mesh results
in no seroma formation, low adhesion, and moderate stretching of the mesh. In contrast
to Surgisis®, Peri-Guard®, and Prolene® meshes, the EDCxCEM mesh showed a statistically
significant increase in the volume fraction (Vv) of collagen (from 34% to 52.1%) in the
central fibrous tissue region at both day 28 and day 56. The statistically high Length
density (Lv), of blood vessels for the EDCxCEM mesh at 28 days was reflected also by the
higher cellular activity (high Vv of fibroblast and moderate Vv of nuclei) indicating
remodelling of this region in the vicinity of a slowly degrading EDCxCEM mesh. The lack of
mesh area stretching/ shrinkage in the EDCxCEM mesh showed that the remodelled tissue
was adequate to prevent hernia formation. The stereo-histological assays suggest that the
EDCxCEM delayed degradation profile supports host wound healing processes including
collagen formation, cellular infiltration, and angiogenesis. The use of cross-linked
cholecyst-derived extracellular matrix for abdominal wall repair is promising
An insight on the N-glycome of notochordal cell-rich porcine nucleus pulposus during maturation.
Degeneration of the intervertebral disc is an age-related condition. It also accompanies the disappearance of the notochordal cells, which are remnants of the developmental stages of the nucleus pulposus (NP). Molecular changes such as extracellular matrix catabolism, cellular phenotype, and glycosaminoglycan loss in the NP have been extensively studied. However, as one of the most significant co- and posttranslational modifications, glycosylation has been overlooked in cells in degeneration. Here, we aim to characterize the N-glycome of young and mature NP and identify patterns related to aging. Accordingly, we isolated N-glycans from notochordal cell-rich NP from porcine discs, characterized them using a combined approach of exoglycosidase digestions and analysis with hydrophilic interaction ultra-performance liquid chromatography and mass spectrometry. We have assigned over 300 individual N-glycans for each age group. Moreover, we observed a notable abundance of antennary structures, galactosylation, fucosylation, and sialylation in both age groups. In addition, as indicated from our results, increasing outer arm fucosylation and decreasing α(2,3)-linked sialylation with aging suggest that these traits are age-dependent. Lastly, we have focused on an extensive characterization of the N-glycome of the notochordal cell-rich NP in aging without inferred degeneration, describing glycosylation changes specific for aging only. Our findings in combination with those of other studies, suggest that the degeneration of the NP does not involve identical processes as aging
Redefining biomaterial biocompatibility: challenges for artificial intelligence and text mining
The surge in ‘Big data’ has significantly influenced biomaterials research and development, with vast data volumes emerging from clinical trials, scientific literature, electronic health records, and other sources. Biocompatibility is essential in developing safe medical devices and biomaterials to perform as intended without provoking adverse reactions. Therefore, establishing an artificial intelligence (AI)-driven biocompatibility definition has become decisive for automating data extraction and profiling safety effectiveness. This definition should both reflect the attributes related to biocompatibility and be compatible with computational data-mining methods. Here, we discuss the need for a comprehensive and contemporary definition of biocompatibility and the challenges in developing one. We also identify the key elements that comprise biocompatibility, and propose an integrated biocompatibility definition that enables data-mining approaches.Peer ReviewedPostprint (published version
Characterization of Biomaterials Intended for Use in the Nucleus Pulposus of Degenerated Intervertebral Discs
Abstract
Biomaterials for regeneration of the intervertebral disc must meet complex requirements conforming to biological, mechanical and clinical demands. Currently no consensus on their characterization exists. It is crucial to identify parameters and their method of characterization for accurate assessment of their potential efficacy, keeping in mind the translation towards clinical application. This review systematically analyzes the characterization techniques of biomaterial systems that have been used for nucleus pulposus (NP) restoration and regeneration. Substantial differences in the approach towards assessment became evident, hindering comparisons between different materials with respect to their suitability for NP restoration and regeneration. We have analyzed the current approaches and identified parameters necessary for adequate biomaterial characterization, with the clinical goal of functional restoration and biological regeneration of the NP in mind. Further, we provide guidelines and goals for their measurement
Macromolecularly crowded in vitro microenvironments accelerate the production of extracellular matrix-rich supramolecular assemblies
Therapeutic strategies based on the principles of tissue engineering by self-assembly put forward the notion that functional regeneration can be achieved by utilising the inherent capacity of cells to create highly sophisticated supramolecular assemblies. However, in dilute ex-vivo microenvironments, prolonged culture time is required to develop an extracellular matrix-rich implantable device. Herein, we assessed the influence of macromolecular crowding, a biophysical phenomenon that regulates intra- and extra-cellular activities in multicellular organisms, in human corneal fibroblast culture. In the presence of macromolecules, abundant extracellular matrix deposition was evidenced as fast as 48 h in culture, even at low serum concentration. Temperature responsive copolymers allowed the detachment of dense and cohesive supramolecularly assembled living substitutes within 6 days in culture. Morphological, histological, gene and protein analysis assays demonstrated maintenance of tissue-specific function. Macromolecular crowding opens new avenues for a more rational design in engineering of clinically relevant tissue modules in vitro
ELASTIN-LIKE RECOMBINAMERS FOR MULTI-MODAL DRUG DELIVERY SYSTEMS
Elastin is a protein with a key role in most of mammalian tissues and it is widely expressed in the extracellular matrix present over myocardium, cartilage and skin. Its elastogenic activity relies on the main cellular components of the tissue network, for instance, endothelial cells, fibroblasts, chondrocytes, and keratinocytes [1]. Nevertheless, the human elastin is naturally synthesized in early age, leading to a drawback based on the low availability, due to the stop in the natural synthetic mechanism with ageing. A clever strategy to overcome such an issue is based on the development of genetically-engineered elastin-mimicking peptides fabrication, so-called elastin-like recombinamers (ELRs), thus balancing the low availability of natural elastin and tuning the biomaterial structuring and behaviour. Relevant advances in the field can derive from the investigation of the morphological, mechanical, in-vitro and delivery-related properties of ELRs-based systems, fabricated in the form of either hydrogel or microspheres. Different scaffold constructs are studied herein, i.e., microspheres, hydrogel and microsphere integrated hydrogel in order to assess their delivery suitability and thoroughly understand the hierarchical complex structuring of the elastin-like recombinamer self- assembly mechanisms. We used two ELRs (1-HRGD6-cyclooctyne, 2-REDV-N3) modified with the two different reactive groups needed to form hydrogels via a click reaction and functionalized with two different bioactive sequences RGD and REDV that would promote cell adhesion. In this study the most stable and optimal concentration ratio of ELRs based hollow spheres exhibited no reduction in cellular metabolic activity. The sacrificial template-based method allowed us to engineer hollow spheres with a first layer of the ELRs HRGD6-component followed by a second layer of the ELRs REDV-component, by means of copper free click-chemistry reaction. The ELRs hollow spheres-tethered ELRs hydrogel was prepared by adding the pre-fabricated ELRs hollow spheres. The hydrogel construct was characterized by rheology, NMR, and Synchrotron Radiation SAXS (SRSAXS). Hollow spheres were characterized by TEM, SEM, DLS and FT-IR. Drug upload and release were assessed by means of ELISA, confocal microscopy and all constructs were successfully tested for cell metabolic activity, revealing no cytotoxicity.
ELR-based hollow microspheres were fabricated and successfully entrapped into an ELR- hydrogel matrix. Release studies have been performed, determining the ELRs platform suitability as drug delivery system
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