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Matrix Embedded Instructional Cues Direct Development and Tissue Repair 2.0
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Matrix Embedded Instructional Cues Direct Development and Tissue Repair 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (15 September 2023) | Viewed by 20132

Special Issue Editors

Prof. Dr. James Melrose

E-Mail Website
Guest Editor
1. Raymond Purves Bone and Joint Research Laboratory, Kolling Institute, Northern Sydney Local Health District, St. Leonards, NSW 2065, Australia
2. Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia
Interests: musculoskeletal disorders; repair biology; GAG pathobiology; stem cells
Special Issues, Collections and Topics in MDPI journals
Dr. Anthony J Hayes

E-Mail Website
Guest Editor
Bioimaging Research Hub, Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK
Interests: development; growth & repair of musculoskeletal connective tissues; extracellular matrix; biological imaging
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Besides being mechanical supports, extracellular and pericellular matrices have long been known to act as scaffolds for cell attachment, also providing regulatory cues that control the cellular proliferation and differentiation of cells within connective tissues. By deciphering this code which controls cellular behavior, it becomes clearer how these could be incorporated into tissue repair strategies to improve the functional recovery of damaged tissues. These repair cues are diverse entities, and have been identified in bioactive peptide modules as well as in specific glycosaminoglycan sequences. The enzymatic processing of extracellular and pericellular matrices can generate these bioactive fragments in pathological tissues; however, intrinsic repair is often unsuccessful unless additional support is provided to affect functional recovery. The aim of this Special Issue is to assemble a collection of papers to further this area of repair biology, which has undergone significant advances particularly in the development of bioactive functional cell directive biomatrices that promote the repair and regeneration of tissues and the recovery of tissue function. Multifunctional tissue proteoglycans with cell regulatory properties participate in many aspects of these repair processes applicable to the promotion of this pathway to functional recovery. Hyaluronan also has significant regulatory properties that promote the cell-directed repair of tissues.

Areas of interest in this Special Issue include: cartilage and tendon repair; the nerve–neuromuscular interface; understanding the roles of proteoglycans in tissue form, function and repair; bioinstructive matrices controlling stem cell behavior that promotes tissue repair; advances in mechano- and electroconductive repair biomatrices; the impact of nanotechnology and 3D printing on tissue repair strategies; bioactive matricryptic ECM component fragments and tissue repair; artificial proteoglycans; understanding the cell directive cues provided by glycosaminoglycans in neural repair; the importance of the ECM in the functional properties of the CNS/PNS; advances in muscular dystrophy repair biology; advances in IVD repair; advances in the vascular repair of connective tissues; HS biology and tissue repair; HA and its roles in the stem cell niche in brain and spinal cord repair; HA, remodeling and repair of the traumatized brain ECM.

Prof. Dr. James Melrose
Dr. Anthony J Hayes
Guest Editors

Manuscript Submission Information

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Keywords

  • extracellular matrix
  • tissue repair
  • repair biology
  • functional recovery

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Related Special Issue

Published Papers (5 papers)

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Research

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15 pages, 8607 KiB  
Article
Developmental Changes in Patterns of Distribution of Fibronectin and Tenascin-C in the Chicken Cornea: Evidence for Distinct and Independent Functions during Corneal Development and Morphogenesis
by Elena Koudouna, Robert D. Young, Andrew J. Quantock and James R. Ralphs
Int. J. Mol. Sci. 2023, 24(4), 3555; https://doi.org/10.3390/ijms24043555 - 10 Feb 2023
Cited by 1 | Viewed by 1745
Abstract
The cornea forms the tough and transparent anterior part of the eye and by accurate shaping forms the major refractive element for vision. Its largest component is the stroma, a dense collagenous connective tissue positioned between the epithelium and the endothelium. In chicken [...] Read more.
The cornea forms the tough and transparent anterior part of the eye and by accurate shaping forms the major refractive element for vision. Its largest component is the stroma, a dense collagenous connective tissue positioned between the epithelium and the endothelium. In chicken embryos, the stroma initially develops as the primary stroma secreted by the epithelium, which is then invaded by migratory neural crest cells. These cells secrete an organised multi-lamellar collagenous extracellular matrix (ECM), becoming keratocytes. Within individual lamellae, collagen fibrils are parallel and orientated approximately orthogonally in adjacent lamellae. In addition to collagens and associated small proteoglycans, the ECM contains the multifunctional adhesive glycoproteins fibronectin and tenascin-C. We show in embryonic chicken corneas that fibronectin is present but is essentially unstructured in the primary stroma before cell migration and develops as strands linking migrating cells as they enter, maintaining their relative positions as they populate the stroma. Fibronectin also becomes prominent in the epithelial basement membrane, from which fibronectin strings penetrate into the stromal lamellar ECM at right angles. These are present throughout embryonic development but are absent in adults. Stromal cells associate with the strings. Since the epithelial basement membrane is the anterior stromal boundary, strings may be used by stromal cells to determine their relative anterior–posterior positions. Tenascin-C is organised differently, initially as an amorphous layer above the endothelium and subsequently extending anteriorly and organising into a 3D mesh when the stromal cells arrive, enclosing them. It continues to shift anteriorly in development, disappearing posteriorly, and finally becoming prominent in Bowman’s layer beneath the epithelium. The similarity of tenascin-C and collagen organisation suggests that it may link cells to collagen, allowing cells to control and organise the developing ECM architecture. Fibronectin and tenascin-C have complementary roles in cell migration, with the former being adhesive and the latter being antiadhesive and able to displace cells from their adhesion to fibronectin. Thus, in addition to the potential for associations between cells and the ECM, the two could be involved in controlling migration and adhesion and subsequent keratocyte differentiation. Despite the similarities in structure and binding capabilities of the two glycoproteins and the fact that they occupy similar regions of the developing stroma, there is little colocalisation, demonstrating their distinctive roles. Full article
(This article belongs to the Special Issue Matrix Embedded Instructional Cues Direct Development and Tissue Repair 2.0)
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16 pages, 5637 KiB  
Article
Chondroitin Sulphate/Dermatan Sulphate Proteoglycans: Potential Regulators of Corneal Stem/Progenitor Cell Phenotype In Vitro
by Kiranjit K. Bains, Sean Ashworth, Elena Koudouna, Robert D. Young, Clare E. Hughes and Andrew J. Quantock
Int. J. Mol. Sci. 2023, 24(3), 2095; https://doi.org/10.3390/ijms24032095 - 20 Jan 2023
Viewed by 2287
Abstract
Chondroitin sulphate (CS) proteoglycans with variable sulphation-motifs along their glycosaminoglycan (GAG) chains are closely associated with the stem cell niche of articular cartilage, where they are believed to influence the characteristics of the resident stem cells. Here, we investigated the immunohistochemical distribution of [...] Read more.
Chondroitin sulphate (CS) proteoglycans with variable sulphation-motifs along their glycosaminoglycan (GAG) chains are closely associated with the stem cell niche of articular cartilage, where they are believed to influence the characteristics of the resident stem cells. Here, we investigated the immunohistochemical distribution of hybrid CS/dermatan sulphate (DS) GAGs in the periphery of the adult chicken cornea, which is the location of the cornea’s stem cell niche in a number of species, using a monoclonal antibody, 6C3, that recognises a sulphation motif-specific CS/DS GAG epitope. This revealed positive labelling that was restricted to the subepithelial corneal stroma, as well as nearby bony structures within the sclera, called ossicles. When cultivated on cell culture dishes coated with 6C3-rich CS/DS, corneal stromal cells (keratocytes) that had been isolated from embryonic chicken corneas formed circular colonies, which took several days to reach confluency. A flow cytometric analysis of these keratocytes revealed changes in their expression levels of the indicative stem cell markers, Connexin 43 (Cx43), Paired Box 6 (PAX6), B-lymphoma Moloney murine leukemia virus insertion region-1 (Bmi-1), and C-X-C Chemokine Receptor 4 (CXCR4) suggestive of a less-differentiated phenotype compared with expression levels in cells not exposed to CS/DS. These findings support the view that CS/DS promotes the retention of a stem cell phenotype in corneal cells, much as it has been proposed to do in other connective tissues. Full article
(This article belongs to the Special Issue Matrix Embedded Instructional Cues Direct Development and Tissue Repair 2.0)
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Review

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39 pages, 3112 KiB  
Review
HS, an Ancient Molecular Recognition and Information Storage Glycosaminoglycan, Equips HS-Proteoglycans with Diverse Matrix and Cell-Interactive Properties Operative in Tissue Development and Tissue Function in Health and Disease
by Anthony J. Hayes and James Melrose
Int. J. Mol. Sci. 2023, 24(2), 1148; https://doi.org/10.3390/ijms24021148 - 6 Jan 2023
Cited by 15 | Viewed by 3460
Abstract
Heparan sulfate is a ubiquitous, variably sulfated interactive glycosaminoglycan that consists of repeating disaccharides of glucuronic acid and glucosamine that are subject to a number of modifications (acetylation, de-acetylation, epimerization, sulfation). Variable heparan sulfate chain lengths and sequences within the heparan sulfate chains [...] Read more.
Heparan sulfate is a ubiquitous, variably sulfated interactive glycosaminoglycan that consists of repeating disaccharides of glucuronic acid and glucosamine that are subject to a number of modifications (acetylation, de-acetylation, epimerization, sulfation). Variable heparan sulfate chain lengths and sequences within the heparan sulfate chains provide structural diversity generating interactive oligosaccharide binding motifs with a diverse range of extracellular ligands and cellular receptors providing instructional cues over cellular behaviour and tissue homeostasis through the regulation of essential physiological processes in development, health, and disease. heparan sulfate and heparan sulfate-PGs are integral components of the specialized glycocalyx surrounding cells. Heparan sulfate is the most heterogeneous glycosaminoglycan, in terms of its sequence and biosynthetic modifications making it a difficult molecule to fully characterize, multiple ligands also make an elucidation of heparan sulfate functional properties complicated. Spatio-temporal presentation of heparan sulfate sulfate groups is an important functional determinant in tissue development and in cellular control of wound healing and extracellular remodelling in pathological tissues. The regulatory properties of heparan sulfate are mediated via interactions with chemokines, chemokine receptors, growth factors and morphogens in cell proliferation, differentiation, development, tissue remodelling, wound healing, immune regulation, inflammation, and tumour development. A greater understanding of these HS interactive processes will improve therapeutic procedures and prognoses. Advances in glycosaminoglycan synthesis and sequencing, computational analytical carbohydrate algorithms and advanced software for the evaluation of molecular docking of heparan sulfate with its molecular partners are now available. These advanced analytic techniques and artificial intelligence offer predictive capability in the elucidation of heparan sulfate conformational effects on heparan sulfate-ligand interactions significantly aiding heparan sulfate therapeutics development. Full article
(This article belongs to the Special Issue Matrix Embedded Instructional Cues Direct Development and Tissue Repair 2.0)
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15 pages, 681 KiB  
Review
Engineering Hyaluronic Acid for the Development of New Treatment Strategies for Osteoarthritis
by Yu Seon Kim and Farshid Guilak
Int. J. Mol. Sci. 2022, 23(15), 8662; https://doi.org/10.3390/ijms23158662 - 4 Aug 2022
Cited by 20 | Viewed by 6548
Abstract
Osteoarthritis (OA) is a degenerative joint disease that is characterized by inflammation of the joints, degradation of cartilage, and the remodeling of other joint tissues. Due to the absence of disease-modifying drugs for OA, current clinical treatment options are often only effective at [...] Read more.
Osteoarthritis (OA) is a degenerative joint disease that is characterized by inflammation of the joints, degradation of cartilage, and the remodeling of other joint tissues. Due to the absence of disease-modifying drugs for OA, current clinical treatment options are often only effective at slowing down disease progression and focus mainly on pain management. The field of tissue engineering has therefore been focusing on developing strategies that could be used not only to alleviate symptoms of OA but also to regenerate the damaged tissue. Hyaluronic acid (HA), an integral component of both the synovial fluid and articular cartilage, has gained widespread usage in developing hydrogels that deliver cells and biomolecules to the OA joint thanks to its biocompatibility and ability to support cell growth and the chondrogenic differentiation of encapsulated stem cells, providing binding sites for growth factors. Tissue-engineering strategies have further attempted to improve the role of HA as an OA therapeutic by developing diverse modified HA delivery platforms for enhanced joint retention and controlled drug release. This review summarizes recent advances in developing HA-based hydrogels for OA treatment and provides additional insights into how HA-based therapeutics could be further improved to maximize their potential as a viable treatment option for OA. Full article
(This article belongs to the Special Issue Matrix Embedded Instructional Cues Direct Development and Tissue Repair 2.0)
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27 pages, 1121 KiB  
Review
Importance of Matrix Cues on Intervertebral Disc Development, Degeneration, and Regeneration
by Matthew J. Kibble, Marco Domingos, Judith A. Hoyland and Stephen M. Richardson
Int. J. Mol. Sci. 2022, 23(13), 6915; https://doi.org/10.3390/ijms23136915 - 21 Jun 2022
Cited by 19 | Viewed by 5303
Abstract
Back pain is one of the leading causes of disability worldwide and is frequently caused by degeneration of the intervertebral discs. The discs’ development, homeostasis, and degeneration are driven by a complex series of biochemical and physical extracellular matrix cues produced by and [...] Read more.
Back pain is one of the leading causes of disability worldwide and is frequently caused by degeneration of the intervertebral discs. The discs’ development, homeostasis, and degeneration are driven by a complex series of biochemical and physical extracellular matrix cues produced by and transmitted to native cells. Thus, understanding the roles of different cues is essential for designing effective cellular and regenerative therapies. Omics technologies have helped identify many new matrix cues; however, comparatively few matrix molecules have thus far been incorporated into tissue engineered models. These include collagen type I and type II, laminins, glycosaminoglycans, and their biomimetic analogues. Modern biofabrication techniques, such as 3D bioprinting, are also enabling the spatial patterning of matrix molecules and growth factors to direct regional effects. These techniques should now be applied to biochemically, physically, and structurally relevant disc models incorporating disc and stem cells to investigate the drivers of healthy cell phenotype and differentiation. Such research will inform the development of efficacious regenerative therapies and improved clinical outcomes. Full article
(This article belongs to the Special Issue Matrix Embedded Instructional Cues Direct Development and Tissue Repair 2.0)
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