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Hyaluronan

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 34403

Special Issue Editor

Dr. Katarína Valachová

E-Mail Website
Guest Editor
Centre of Experimental Medicine of Slovak Academy of Sciences, Dubravska cesta 9, 84104 Bratislava, Slovakia
Interests: hyaluronan; reactive oxygen species; drugs; antioxidants; biopolymers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Hyaluronan (HA) is a natural glycosaminoglycan present in all vertebrates in many tissues. HA has various biological functions, which depend on its molar mass. HA has antioxidant properties; however, it can be readily degraded by reactive oxygen species. For many years, it has been used in treatment of osteoarthritis, ophthalmology, and in cosmetics. In recent years there has been a growing interest in HA to be applied also in other fields of medicine such as dentistry, skin wound healing, gene delivery, and tissue engineering.

Dr. Katarína Valachová
Guest Editor

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Keywords

  • hyaluronan
  • hyaluronan degradation
  • cosmetics
  • medicine
  • reactive oxygen species

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Related Special Issue

Published Papers (7 papers)

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Research

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15 pages, 3795 KiB  
Article
Multidose Hyaluronidase Administration as an Optimal Procedure to Degrade Resilient Hyaluronic Acid Soft Tissue Fillers
by Killian Flégeau, Jing Jing, Romain Brusini, Mélanie Gallet, Capucine Moreno, Lee Walker, François Bourdon and Jimmy Faivre
Molecules 2023, 28(3), 1003; https://doi.org/10.3390/molecules28031003 - 19 Jan 2023
Cited by 10 | Viewed by 4481
Abstract
Minimally invasive hyaluronan (HA) tissue fillers are routinely employed to provide tissue projection and correct age-related skin depressions. HA fillers can advantageously be degraded by hyaluronidase (HAase) administration in case of adverse events. However, clear guidelines regarding the optimal dosage and mode of [...] Read more.
Minimally invasive hyaluronan (HA) tissue fillers are routinely employed to provide tissue projection and correct age-related skin depressions. HA fillers can advantageously be degraded by hyaluronidase (HAase) administration in case of adverse events. However, clear guidelines regarding the optimal dosage and mode of administration of HAase are missing, leaving a scientific gap for practitioners in their daily practice. In this study, we implemented a novel rheological procedure to rationally evaluate soft tissue filler degradability and optimize their degradation kinetics. TEOSYAL RHA® filler degradation kinetics in contact with HAase was monitored in real-time by rheological time sweeps. Gels were shown to degrade as a function of enzymatic activity, HA concentration, and BDDE content, with a concomitant loss of their viscoelastic properties. We further demonstrated that repeated administration of small HAase doses improved HA degradation kinetics over large single doses. Mathematical analyses were developed to evaluate the degradation potential of an enzyme. Finally, we tuned the optimal time between injections and number of enzymatic units, maximizing degradation kinetics. In this study, we have established a scientific rationale for the degradation of HA fillers by multidose HAase administration that could serve as a basis for future clinical management of adverse events. Full article
(This article belongs to the Special Issue Hyaluronan)
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12 pages, 1901 KiB  
Article
Glucocorticoids Directly Affect Hyaluronan Production of Orbital Fibroblasts; A Potential Pleiotropic Effect in Graves’ Orbitopathy
by Erika Galgoczi, Monika Katko, Fruzsina Reka Papp, Robert Csiki, Sara Csiha, Annamaria Erdei, Miklos Bodor, Bernadett Ujhelyi, Zita Steiber, Ferenc Gyory and Endre V. Nagy
Molecules 2023, 28(1), 15; https://doi.org/10.3390/molecules28010015 - 20 Dec 2022
Cited by 2 | Viewed by 1748
Abstract
Orbital connective tissue expansion is a hallmark of Graves’ orbitopathy (GO). In moderate-to-severe active GO, glucocorticoids (GC) are the first line of treatment. Here we show that hydrocortisone (HC), prednisolone (P), methylprednisolone (MP), and dexamethasone (DEX) inhibit the hyaluronan (HA) production of orbital [...] Read more.
Orbital connective tissue expansion is a hallmark of Graves’ orbitopathy (GO). In moderate-to-severe active GO, glucocorticoids (GC) are the first line of treatment. Here we show that hydrocortisone (HC), prednisolone (P), methylprednisolone (MP), and dexamethasone (DEX) inhibit the hyaluronan (HA) production of orbital (OF) and dermal (DF) fibroblasts. HA production of GO OFs (n = 4), NON-GO OFs (n = 4) and DFs (n = 4) was measured by ELISA. mRNA expression of enzymes of HA metabolism and fibroblast proliferation was examined by RT-PCR and BrdU incorporation, respectively. After 24 h of GC treatment (1µM) HA production decreased by an average of 67.9 ± 3.11% (p < 0.0001) in all cell cultures. HAS2, HAS3 and HYAL1 expression in OFs also decreased (p = 0.009, p = 0.0005 and p = 0.015, respectively). Ten ng/mL PDGF-BB increased HA production and fibroblast proliferation in all cell lines (p < 0.0001); GC treatment remained effective and reduced HA production under PDGF-BB-stimulated conditions (p < 0.0001). MP and DEX reduced (p < 0.001, p = 0.002, respectively) PDGF-BB-induced HAS2 expression in OFs. MP and DEX treatment decreased PDGF-BB stimulated HAS3 expression (p = 0.035 and p = 0.029, respectively). None of the GCs tested reduced the PDGF-BB stimulated proliferation rate. Our results confirm that GCs directly reduce the HA production of OFs, which may contribute to the beneficial effect of GCs in GO. Full article
(This article belongs to the Special Issue Hyaluronan)
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13 pages, 3672 KiB  
Article
Preparation and Physicochemical Characterization of Gelatin–Aldehyde Derivatives
by Mahmoud Atya El-Meligy, Katarína Valachová, Ivo Juránek, Tamer M. Tamer and Ladislav Šoltés
Molecules 2022, 27(20), 7003; https://doi.org/10.3390/molecules27207003 - 18 Oct 2022
Cited by 13 | Viewed by 2036
Abstract
The present study aimed at preparing novel free-radical scavenging and water-soluble compounds derived from gelatin. Specifically, gelatin–syringaldehyde, gelatin–anisaldehyde, and gelatin–vanillin were synthesized and thoroughly studied for their physicochemical properties. In particular, the compounds were characterized by UV-Vis spectroscopy, Fourier-transform infrared spectroscopy, and scanning [...] Read more.
The present study aimed at preparing novel free-radical scavenging and water-soluble compounds derived from gelatin. Specifically, gelatin–syringaldehyde, gelatin–anisaldehyde, and gelatin–vanillin were synthesized and thoroughly studied for their physicochemical properties. In particular, the compounds were characterized by UV-Vis spectroscopy, Fourier-transform infrared spectroscopy, and scanning electron microscopy. Notably, as demonstrated by thermogravimetry and differential scanning calorimetry, all three derivatives exhibited higher thermal stability than gelatin itself. Free-radical scavenging activities of the examined compounds were explored by (i) a standard spectrophotometric ABTS assay and (ii) an assay of oxidative degradation of hyaluronic acid monitored by rotational viscometry. We found that gelatin and gelatin–syringaldehyde demonstrated the highest efficacy in scavenging •OH radicals, whereas gelatin–anisaldehyde was the least effective. The efficacy of scavenging alkyloxy- and alkylperoxy-type free radicals via hydrogen-atom-transferring property was in the following order: gelatin > gelatin–vanillin > gelatin–syringaldehyde > gelatin–anisaldehyde. Electron-donor properties determined using the ABTS assay revealed the following order in one-electron reduction of ABTS•+: gelatin > gelatin–anisaldehyde > gelatin–vanillin > gelatin–syringaldehyde. Full article
(This article belongs to the Special Issue Hyaluronan)
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13 pages, 1295 KiB  
Article
LncRNA MALAT1 Participates in Protection of High-Molecular-Weight Hyaluronan against Smoke-Induced Acute Lung Injury by Upregulation of SOCS-1
by Shaoguang Li, Bin Li, Ke Lang, Yubei Gong, Xiang Cheng, Shufen Deng, Qiwen Shi and Hang Zhao
Molecules 2022, 27(13), 4128; https://doi.org/10.3390/molecules27134128 - 27 Jun 2022
Cited by 3 | Viewed by 1857
Abstract
Smoke-induced acute lung injury (ALI) is a grievous disease with high mortality. Despite advances in medical intervention, no drug has yet been approved by the Food and Drug Administration (FDA) for ALI. In this study, we reported that pretreatment with high-molecular-weight hyaluronan (1600 [...] Read more.
Smoke-induced acute lung injury (ALI) is a grievous disease with high mortality. Despite advances in medical intervention, no drug has yet been approved by the Food and Drug Administration (FDA) for ALI. In this study, we reported that pretreatment with high-molecular-weight hyaluronan (1600 kDa, HA1600) alleviated pulmonary inflammation and injury in mice exposed to smoke and also upregulated long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), as well as suppressor of cytokine signaling-1 (SOCS-1), in the lung tissues. Next, we overexpressed MALAT1 in the lungs by intratracheal administration of adenovirus cloned with MALAT1 cDNA and found that the survival of mice after smoke exposure was improved. Moreover, pulmonary overexpression of MALAT1 ameliorated smoke-induced ALI in mice and elevated the level of SOCS-1 in the lungs. In conclusion, the results pointed out that HA1600 exerted a protective effect against smoke-induced ALI through increasing the MALAT1 level and the subsequent SOCS-1 expression. Our study provides a potential therapeutic approach to smoke-induced ALI and a novel insight into the mechanism of action of HA1600. Full article
(This article belongs to the Special Issue Hyaluronan)
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15 pages, 7443 KiB  
Article
N-Butyrylated Hyaluronic Acid Achieves Anti-Inflammatory Effects In Vitro and in Adjuvant-Induced Immune Activation in Rats
by Xue Luan, Zhongcheng Cong, Tassos P. Anastassiades and Yin Gao
Molecules 2022, 27(10), 3267; https://doi.org/10.3390/molecules27103267 - 19 May 2022
Cited by 7 | Viewed by 2675
Abstract
Previously synthesized N-butyrylated hyaluronic acid (BHA) provides anti-inflammatory effects in rat models of acute gouty arthritis and hyperuricemia. However, the mechanism of action remains to be elucidated. Herein, the anti-inflammatory and antioxidative activities of BHA and the targeted signaling pathways were explored [...] Read more.
Previously synthesized N-butyrylated hyaluronic acid (BHA) provides anti-inflammatory effects in rat models of acute gouty arthritis and hyperuricemia. However, the mechanism of action remains to be elucidated. Herein, the anti-inflammatory and antioxidative activities of BHA and the targeted signaling pathways were explored with LPS-induced RAW264.7 and an adjuvant-induced inflammation in a rat model. Results indicated that BHA inhibited the generation of pro-inflammatory cytokines TNFα, IL-1β and IL-6, reduced ROS production and down-regulated JAK1-STAT1/3 signaling pathways in LPS-induced RAW264.7. In vivo, BHA alleviated paw and joint swelling, decreased inflammatory cell infiltration in paw tissues, suppressed gene expressions of p38 and p65, down-regulated the NF-κB and MAPK signaling pathways and reduced protein levels of TNFα, IL-1β and IL-6 in joint tissues of arthritis rats. This study demonstrated the pivotal role of BHA in anti-inflammation and anti-oxidation, suggesting the potential clinical value of BHA in the prevention of inflammatory arthritis and is worthy for development as a new pharmacological treatment. Full article
(This article belongs to the Special Issue Hyaluronan)
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Review

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27 pages, 2039 KiB  
Review
Atomic-Resolution Experimental Structural Biology and Molecular Dynamics Simulations of Hyaluronan and Its Complexes
by Olgun Guvench
Molecules 2022, 27(21), 7276; https://doi.org/10.3390/molecules27217276 - 26 Oct 2022
Cited by 6 | Viewed by 2500
Abstract
This review summarizes the atomic-resolution structural biology of hyaluronan and its complexes available in the Protein Data Bank, as well as published studies of atomic-resolution explicit-solvent molecular dynamics simulations on these and other hyaluronan and hyaluronan-containing systems. Advances in accurate molecular mechanics force [...] Read more.
This review summarizes the atomic-resolution structural biology of hyaluronan and its complexes available in the Protein Data Bank, as well as published studies of atomic-resolution explicit-solvent molecular dynamics simulations on these and other hyaluronan and hyaluronan-containing systems. Advances in accurate molecular mechanics force fields, simulation methods and software, and computer hardware have supported a recent flourish in such simulations, such that the simulation publications now outnumber the structural biology publications by an order of magnitude. In addition to supplementing the experimental structural biology with computed dynamic and thermodynamic information, the molecular dynamics studies provide a wealth of atomic-resolution information on hyaluronan-containing systems for which there is no atomic-resolution structural biology either available or possible. Examples of these summarized in this review include hyaluronan pairing with other hyaluronan molecules and glycosaminoglycans, with ions, with proteins and peptides, with lipids, and with drugs and drug-like molecules. Despite limitations imposed by present-day computing resources on system size and simulation timescale, atomic-resolution explicit-solvent molecular dynamics simulations have been able to contribute significant insight into hyaluronan’s flexibility and capacity for intra- and intermolecular non-covalent interactions. Full article
(This article belongs to the Special Issue Hyaluronan)
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38 pages, 8010 KiB  
Review
Bridging a Century-Old Problem: The Pathophysiology and Molecular Mechanisms of HA Filler-Induced Vascular Occlusion (FIVO)—Implications for Therapeutic Interventions
by Danny J. Soares MD
Molecules 2022, 27(17), 5398; https://doi.org/10.3390/molecules27175398 - 24 Aug 2022
Cited by 25 | Viewed by 17676
Abstract
Biocompatible hyaluronic acid (HA, hyaluronan) gel implants have altered the therapeutic landscape of surgery and medicine, fostering an array of innovative products that include viscosurgical aids, synovial supplements, and drug-eluting nanomaterials. However, it is perhaps the explosive growth in the cosmetic applications of [...] Read more.
Biocompatible hyaluronic acid (HA, hyaluronan) gel implants have altered the therapeutic landscape of surgery and medicine, fostering an array of innovative products that include viscosurgical aids, synovial supplements, and drug-eluting nanomaterials. However, it is perhaps the explosive growth in the cosmetic applications of injectable dermal fillers that has captured the brightest spotlight, emerging as the dominant modality in plastic surgery and aesthetic medicine. The popularity surge with which injectable HA fillers have risen to in vogue status has also brought a concomitant increase in the incidence of once-rare iatrogenic vaso-occlusive injuries ranging from disfiguring facial skin necrosis to disabling neuro-ophthalmological sequelae. As our understanding of the pathophysiology of these injuries has evolved, supplemented by more than a century of astute observations, the formulation of novel therapeutic and preventative strategies has permitted the amelioration of this burdensome complication. In this special issue article, we review the relevant mechanisms underlying HA filler-induced vascular occlusion (FIVO), with particular emphasis on the rheo-mechanical aspects of vascular blockade; the thromboembolic potential of HA mixtures; and the tissue-specific ischemic susceptibility of microvascular networks, which leads to underperfusion, hypoxia, and ultimate injury. In addition, recent therapeutic advances and novel considerations on the prevention and management of muco-cutaneous and neuro-ophthalmological complications are examined. Full article
(This article belongs to the Special Issue Hyaluronan)
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