Submit to Biomolecules Review for Biomolecules Propose a Special Issue

Journal Browser

► Journal Browser

Hyaluronic Acid in Human Medicine

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Biological Factors".

Deadline for manuscript submissions: closed (10 April 2022) | Viewed by 43853

Share This Special Issue

Special Issue Editor

Dr. Jakub Suchánek

E-Mail Website
Guest Editor

Department of Dentistry, Faculty of Medicine in Hradec Kralove, Charles University and University Hospital Hradec Kralove, 500 05 Hradec Kralove, Czech Republic
Interests: dental pulp stem cells; endodontics; dental caries; hyaluronic acid

Special Issue Information

Dear Colleagues,

Hyaluronic acid (HA) is an acidic, non-sulfated glycosaminoglycan that is intensively studied as biodegradable and biocompatible material for scaffolding, regenerative medicine, and clinical aplications. As the ubiquitous component of the extracellular matrix, HA is widely distributed in the human body and can be found in the umbilical cord, synovial fluid, dental pulp, vitreum, or epithelial and connective tissues. The main functions of HA are hydration, space-filling capacity, lubrication, and forming of the framework through which cells migrate. It also contributes to fetal healing of wounds, i.e., rapid healing without a scar, and tissue elasticity. However, there are additional properties of HA that are various based on the length of its molecular chain. In the human body, HA is synthesized and dominantly presented in high molecular weight; thus long-chain molecules of HA are a part of the natural environment of cells. During the degradation of HA, which is accelerated under pathological conditions, its long molecules are cleaved into smaller fragments of low molecular weight. Bioactive functions in the inflammatory reaction, angiogenesis, or its role in cancer progression and reactive oxygen species scavenging vary for different fractions of HA.

In tissue engineering, HA is considered a promising material thanks to its biocompatible, biodegradable, and bioresorbable properties, as well as its chemical traits and high level of technical processing. Based on the processing method, HA can be produced in many forms and shapes, e.g., gels of various viscosity, porous, sponge-like scaffolds, fibers, sutures, surgical dressings, or micro and nanomaterials. Additionally, its chemical modifications offer further modifications, resulting in enhanced or modulated properties. As such, HA provides a broad spectrum of possible applications in nearly every field of biomedicine.

Dr. Jakub Suchánek
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Hyaluronic acid
Hyaluronan
Wound healing
Clinical trials
Regenerative medicine
Hyaluronic acid derivatives

Published Papers (12 papers)

Download All Papers

Editorial

Jump to: Research, Review, Other

3 pages, 200 KiB

Open AccessEditorial

Editorial of Special Issue “Hyaluronic Acid in Human Medicine”

by Jakub Suchánek

Biomolecules 2022, 12(10), 1495; https://doi.org/10.3390/biom12101495 - 17 Oct 2022

Viewed by 954

Abstract

Hyaluronic acid (HA) is an acidic, non-sulfated glycosaminoglycan that is intensively studied as a biodegradable and biocompatible material for scaffolding, regenerative medicine, and clinical applications [...] Full article

(This article belongs to the Special Issue Hyaluronic Acid in Human Medicine)

Research

Jump to: Editorial, Review, Other

17 pages, 6212 KiB

Open AccessArticle

Innovative Approach in the Cryogenic Freezing Medium for Mesenchymal Stem Cells

by Nela Pilbauerova, Jan Schmidt, Tomas Soukup, Tomas Prat, Kristina Nesporova, Vladimir Velebny and Jakub Suchanek

Biomolecules 2022, 12(5), 610; https://doi.org/10.3390/biom12050610 - 20 Apr 2022

Cited by 5 | Viewed by 2885

Abstract

The physical stresses during cryopreservation affect stem cell survival and further proliferation. To minimize or prevent cryoinjury, cryoprotective agents (CPAs) are indispensable. Despite the widespread use of 10% dimethyl sulfoxide (DMSO), there are concerns about its potential adverse effects. To bypass those effects, combinations of CPAs have been investigated. This study aimed to verify whether high-molecular-hyaluronic acid (HMW-HA) serves as a cryoprotectant when preserving human mesenchymal stem cells (hMSCs) to reduce the DMSO concentration in the cryopreservation medium. We studied how 0.1% or 0.2% HMW-HA combined with reduced DMSO concentrations (from 10% to 5%, and 3%) affected total cell count, viability, immunophenotype, and differentiation potential post-cryopreservation. Immediately after cell revival, the highest total cell count was observed in 10% DMSO-stored hMSC. However, two weeks after cell cultivation an increased cell count was seen in the HMW-HA-stored groups along with a continued increase in hMSCs stored using 3% DMSO and 0.1% HMW-HA. The increased total cell count corresponded to elevated expression of stemness marker CD49f. The HA-supplemented cryomedium did not affect the differential potential of hMSC. Our results will participate in producing a ready-to-use product for cryopreservation of mesenchymal stem cells. Full article

(This article belongs to the Special Issue Hyaluronic Acid in Human Medicine)

► Show Figures

Graphical abstract

17 pages, 4432 KiB

Open AccessArticle

The Degradation of Hyaluronan in the Skin

by Petra Žádníková, Romana Šínová, Vojtěch Pavlík, Matěj Šimek, Barbora Šafránková, Martina Hermannová, Kristina Nešporová and Vladimír Velebný

Biomolecules 2022, 12(2), 251; https://doi.org/10.3390/biom12020251 - 3 Feb 2022

Cited by 28 | Viewed by 5271

Abstract

Hyaluronan (HA) comprises a fundamental component of the extracellular matrix and participates in a variety of biological processes. Half of the total amount of HA in the human body is present in the skin. HA exhibits a dynamic turnover; its half-life in the skin is less than one day. Nevertheless, the specific participants in the catabolism of HA in the skin have not yet been described in detail, despite the essential role of HA in cutaneous biology. A deeper knowledge of the processes involved will act to support the development of HA-based topical and implantable materials and enhance the understanding of the various related pathological cutaneous conditions. This study aimed to characterize the distribution and activity of hyaluronidases and the other proteins involved in the degradation of HA in healthy human full-thickness skin, the epidermis and the dermis. Hyaluronidase activity was detected for the first time in healthy human skin. The degradation of HA occurred in lysates at an acidic pH. HA gel zymography revealed a single band corresponding to approximately 50 kDa. This study provided the first comprehensive view of the distribution of canonic HA-degrading proteins (HYAL1 and HYAL2) in human skin employing IHF and IHC. Furthermore, contrary to previous assumptions TMEM2, a novel hyaluronidase, as well as CEMIP, a protein involved in HA degradation, were localized in the human epidermis, as well as in the dermis. Full article

(This article belongs to the Special Issue Hyaluronic Acid in Human Medicine)

► Show Figures

Figure 1

14 pages, 2584 KiB

Open AccessArticle

Retinoic Acid Grafted to Hyaluronic Acid Activates Retinoid Gene Expression and Removes Cholesterol from Cellular Membranes

by Vojtěch Pavlík, Veronika Machalová, Martin Čepa, Romana Šínová, Barbora Šafránková, Jaromír Kulhánek, Tomáš Drmota, Lukáš Kubala, Gloria Huerta-Ángeles, Vladimír Velebný and Kristina Nešporová

Biomolecules 2022, 12(2), 200; https://doi.org/10.3390/biom12020200 - 25 Jan 2022

Cited by 4 | Viewed by 3121

Abstract

All-trans-retinoic acid (atRA) is a potent ligand that regulates gene expression and is used to treat several skin disorders. Hyaluronic acid (HA) was previously conjugated with atRA (HA-atRA) to obtain a novel amphiphilic compound. HA-atRA forms micelles that incorporate hydrophobic molecules and facilitate their transport through the skin. The aim of this study was to determine the influence of HA-atRA on gene expression in skin cells and to compare it with that of unbound atRA. Gene expression was investigated using microarrays and a luciferase system with a canonical atRA promoter. HA-atRA upregulated gene expression similarly to atRA. However, HA-atRA activated the expression of cholesterol metabolism genes, unlike atRA. Further investigation using HPLC and filipin III staining suggested that the treated cells induced cholesterol synthesis to replenish the cholesterol removed from the cells by HA-atRA. HA modified with oleate (HA-C18:1) removed cholesterol from the cells similarly to HA-atRA, suggesting that the cholesterol removal stemmed from the amphiphilic nature of the two derivatives. HA-atRA induces retinoid signaling. Thus, HA-atRA could be used to treat skin diseases, such as acne and psoriasis, where the combined action of atRA signaling and anti-inflammatory cholesterol removal may be potentially beneficial. Full article

(This article belongs to the Special Issue Hyaluronic Acid in Human Medicine)

► Show Figures

Figure 1

16 pages, 5990 KiB

Open AccessArticle

Nonwoven Textiles from Hyaluronan for Wound Healing Applications

by Jolana Kubíčková, Tomáš Medek, Jarmila Husby, Jana Matonohová, Hana Vágnerová, Lucie Marholdová, Vladimír Velebný and Josef Chmelař

Biomolecules 2022, 12(1), 16; https://doi.org/10.3390/biom12010016 - 23 Dec 2021

Cited by 7 | Viewed by 3393

Abstract

Nonwoven textiles are used extensively in the field of medicine, including wound healing, but these textiles are mostly from conventional nondegradable materials, e.g., cotton or synthetic polymers such as polypropylene. Therefore, we aimed to develop nonwoven textiles from hyaluronan (HA), a biocompatible, biodegradable and nontoxic polysaccharide naturally present in the human body. For this purpose, we used a process based on wet spinning HA into a nonstationary coagulation bath combined with the wet-laid textile technology. The obtained HA nonwoven textiles are soft, flexible and paper like. Their mechanical properties, handling and hydration depend on the microscale fibre structure, which is tuneable by selected process parameters. Cell viability testing on two relevant cell lines (3T3, HaCaT) demonstrated that the textiles are not cytotoxic, while the monocyte activation test ruled out pyrogenicity. Biocompatibility, biodegradability and their high capacity for moisture absorption make HA nonwoven textiles a promising material for applications in the field of wound healing, both for topical and internal use. The beneficial effect of HA in the process of wound healing is well known and the form of a nonwoven textile should enable convenient handling and application to various types of wounds. Full article

(This article belongs to the Special Issue Hyaluronic Acid in Human Medicine)

► Show Figures

Graphical abstract

11 pages, 1175 KiB

Open AccessArticle

Long-Lasting Effect after Single Hyaluronate Injection for Unilateral Vocal Fold Paralysis: Does Concentration Matter?

by Yi-Chieh Lee, Yu-Cheng Pei, Yi-An Lu, Hsiu-Feng Chung, Hsueh-Yu Li, Li-Ang Lee and Tuan-Jen Fang

Biomolecules 2021, 11(11), 1580; https://doi.org/10.3390/biom11111580 - 26 Oct 2021

Cited by 4 | Viewed by 1770

Abstract

Background: Early injection laryngoplasty (EIL) using hyaluronic acid (HA) is an effective treatment for glottic insufficiency in patients with acute unilateral vocal fold paralysis (UVFP). Most patients benefit by showing improvement in voice and quality of life and implied reduced need for permanent laryngoplasty. However, injected HA might resolve within a short period, so its long-term outcomes and the need for secondary procedures need to be clarified. Methods: Patients who underwent EIL with HA for acute UVFP from January 2015 to December 2018 were included. The factors that may associate with the prognosis including voice performance and laryngeal configuration at presentation, the cause of UVFP, and the type of HA for EIL were analyzed. Results: Ninety-four patients were included for analysis, with a mean follow-up period of 25.1 months (95% CI: 22.8–27.4 months). After primary HA injection, 22 patients (23.4%) underwent secondary procedures (rate: 13.1% per person-year), and most (63.6%) of the events occurred after one year from the first injection. The rate of secondary procedures within the first 12 months was 9.0% (14.1% and 4.3% for low-concentrated HA (LHA) and high-concentrated HA (HHA), respectively). The incidence of the secondary procedures was higher in the LHA group (18.2%) (p = 0.026) than in the HHA group (7.5%). Conclusions: The rate of secondary procedures was lower than the prediction based on the resorption time of HA, a finding that could be partly accounted for by both natural nerve recovery and a long-lasting effect of EIL. EIL with HHA had a lower rate of re-treatment than that with LHA, suggesting a better clinical utility for acute UVFP. Full article

(This article belongs to the Special Issue Hyaluronic Acid in Human Medicine)

► Show Figures

Figure 1

7 pages, 248 KiB

Open AccessFeature PaperArticle

Assessment of the Response Profile to Hyaluronic Acid Plus Sorbitol Injection in Patients with Knee Osteoarthritis: Post-Hoc Analysis of a 6-Month Randomized Controlled Trial

by Olivier Bruyère, Germain Honvo, Eduard Vidovic and Bernard Cortet

Biomolecules 2021, 11(10), 1498; https://doi.org/10.3390/biom11101498 - 11 Oct 2021

Cited by 7 | Viewed by 2546

Abstract

In a previous randomized trial, the non-inferiority of two hyaluronic acid injections (Synolis VA versus Synvisc-One) was assessed in patients with knee OA, with a response rate of 79% for Synolis VA. To assess whether a responder profile could be established for this treatment modality, we used the Synolis VA arm of a published 6-month prospective, multicenter, comparative, randomized, double-blinded trial. At baseline and during the study, pain and function were assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire. Ninety-six subjects from the intention-to-treat trial were included in the analysis. The 6-month change of WOMAC Pain with Synolis VA was not associated with any baseline clinical data. However, the change in WOMAC Function was significantly associated with its baseline level, even after adjustment for potential confounding variables (p = 0.028), i.e., a poorer physical function at baseline was associated with a better response. In conclusion, in addition to the high absolute response rate to Synolis VA, the probability of success is even increased if administered in patients with more limited physical function at baseline. Further research with other potential confounding clinical variables is warranted in order to better applicate the concept of personalized medicine. Full article

(This article belongs to the Special Issue Hyaluronic Acid in Human Medicine)

15 pages, 2739 KiB

Open AccessArticle

Insight into the Lubrication and Adhesion Properties of Hyaluronan for Ocular Drug Delivery

by Mikuláš Černohlávek, Martina Brandejsová, Petr Štěpán, Hana Vagnerová, Martina Hermannová, Kateřina Kopecká, Jaromír Kulhánek, David Nečas, Martin Vrbka, Vladimir Velebný and Gloria Huerta-Angeles

Biomolecules 2021, 11(10), 1431; https://doi.org/10.3390/biom11101431 - 30 Sep 2021

Cited by 11 | Viewed by 3511

Abstract

Hyaluronan (HA) is widely used for eye drops as lubricant to counteract dry eye disease. High and low molecular weight HA are currently used in ophthalmology. However, a large portion of the current literature on friction and lubrication addresses articular (joint) cartilage. Therefore, eye drops compositions based on HA and its derivatized forms are extensively characterized providing data on the tribological and mucoadhesive properties. The physiochemical properties are investigated in buffers used commonly in eye drops formulations. The tribological investigation reveals that amphiphilic HA-C12 decreases the friction coefficient. At the same time, the combination of trehalose/HA or HAC12 enhances up to eighty-fold the mucoadhesiveness. Thus, it is predicted a prolonged residence time on the surface of the eye. The incorporation of trehalose enhances the protection of human keratinocytes (HaCaT) cells, as demonstrated in an in-vitro cell-desiccation model. The presence of trehalose increases the friction coefficient. Medium molecular weight HA shows significantly lower friction coefficient than high molecular weight HA. This research represents a first, wide array of features of diverse HA forms for eye drops contributing to increase the knowledge of these preparations. The results here presented also provide valuable information for the design of highly performing HA-formulations addressing specific needs before preclinic. Full article

(This article belongs to the Special Issue Hyaluronic Acid in Human Medicine)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research, Other

16 pages, 1240 KiB

Open AccessReview

Lung Hyaluronasome: Involvement of Low Molecular Weight Ha (Lmw-Ha) in Innate Immunity

by Antony Hoarau, Myriam Polette and Christelle Coraux

Biomolecules 2022, 12(5), 658; https://doi.org/10.3390/biom12050658 - 30 Apr 2022

Cited by 13 | Viewed by 2983

Abstract

Hyaluronic acid (HA) is a major component of the extracellular matrix. It is synthesized by hyaluronan synthases (HAS) into high-molecular-weight chains (HMW-HA) that exhibit anti-inflammatory and immunomodulatory functions. In damaged, infected, and/or inflamed tissues, HMW-HA are degraded by hyaluronidases (HYAL) or reactive oxygen species (ROS) to give rise to low-molecular-weight HAs (LMW-HAs) that are potent pro-inflammatory molecules. Therefore, the size of HA regulates the balance of anti- or pro-inflammatory functions. The activities of HA depend also on its interactions with hyaladherins. HA synthesis, degradation, and activities through HA/receptors interactions define the hyaluronasome. In this review, a short overview of the role of high and low-molecular-weight HA polymers in the lungs is provided. The involvement of LMW-HA in pulmonary innate immunity via the activation of neutrophils, macrophages, dendritic cells, and epithelial cells is described to highlight LMW-HA as a therapeutic target in inflammatory respiratory diseases. Finally, the possibilities to counter LMW-HA’s deleterious effects in the lungs are discussed. Full article

(This article belongs to the Special Issue Hyaluronic Acid in Human Medicine)

► Show Figures

Figure 1

17 pages, 4441 KiB

Open AccessReview

Endogenously-Produced Hyaluronan and Its Potential to Regulate the Development of Peritoneal Adhesions

by Anna Kocurkova, Kristina Nesporova, Miriam Sandanusova, Michaela Kerberova, Katerina Lehka, Vladimir Velebny, Lukas Kubala and Gabriela Ambrozova

Biomolecules 2022, 12(1), 45; https://doi.org/10.3390/biom12010045 - 29 Dec 2021

Cited by 4 | Viewed by 2371

Abstract

Formation of peritoneal adhesions (PA) is one of the major complications following intra-abdominal surgery. It is primarily caused by activation of the mesothelial layer and underlying tissues in the peritoneal membrane resulting in the transition of mesothelial cells (MCs) and fibroblasts to a pro-fibrotic phenotype. Pro-fibrotic transition of MCs—mesothelial-to-mesenchymal transition (MMT), and fibroblasts activation to myofibroblasts are interconnected to changes in cellular metabolism and culminate in the deposition of extracellular matrix (ECM) in the form of fibrotic tissue between injured sides in the abdominal cavity. However, ECM is not only a mechanical scaffold of the newly synthetized tissue but reciprocally affects fibrosis development. Hyaluronan (HA), an important component of ECM, is a non-sulfated glycosaminoglycan consisting of N-acetyl-D-glucosamine (GlcNAc) and D-glucuronic acid (GlcUA) that can affect the majority of processes involved in PA formation. This review considers the role of endogenously produced HA in the context of different fibrosis-related pathologies and its overlap in the development of PA. Full article

(This article belongs to the Special Issue Hyaluronic Acid in Human Medicine)

► Show Figures

Figure 1

34 pages, 8749 KiB

Open AccessEditor’s ChoiceReview

Hyaluronic Acid: A Key Ingredient in the Therapy of Inflammation

by Andreia Marinho, Cláudia Nunes and Salette Reis

Biomolecules 2021, 11(10), 1518; https://doi.org/10.3390/biom11101518 - 15 Oct 2021

Cited by 115 | Viewed by 10043

Abstract

Hyaluronic acid (HA) is a natural polymer, produced endogenously by the human body, which has unique physicochemical and biological properties, exhibiting desirable biocompatibility and biodegradability. Therefore, it has been widely studied for possible applications in the area of inflammatory diseases. Although exogenous HA has been described as unable to restore or replace the properties and activities of endogenous HA, it can still provide satisfactory pain relief. This review aims to discuss the advances that have been achieved in the treatment of inflammatory diseases using hyaluronic acid as a key ingredient, essentially focusing on studies carried out between the years 2017 and 2021. Full article

(This article belongs to the Special Issue Hyaluronic Acid in Human Medicine)

► Show Figures

Figure 1

Other

Jump to: Editorial, Research, Review

10 pages, 2365 KiB

Open AccessCase Report

Initial Observation of Factors Interfering with the Treatment of Alveolar Osteitis Using Hyaluronic Acid with Octenidine—A Series of Case Reports

by Martin Kapitán, Jan Schmidt, Radovan Mottl and Nela Pilbauerová

Biomolecules 2021, 11(8), 1157; https://doi.org/10.3390/biom11081157 - 4 Aug 2021

Cited by 4 | Viewed by 2332

Abstract

Alveolar osteitis (AO) is a common complication following the extraction of the teeth, particularly the lower third molars. It starts within a few days after the extraction and manifests mainly as pain in the extraction site. Several strategies of treatment are available in order to relieve pain and heal the extraction wound. Recently, a novel medical device combining hyaluronic acid (HA) and octenidine (OCT) was introduced for the treatment of AO. This series of case reports aims to summarize the initial clinical experiences with this new device and to highlight factors possibly interfering with this treatment. The medical documentation of five patients with similar initial situations treated for AO with HA + OCT device was analyzed in detail. Smoking and previous treatment with Alveogyl (Septodont, Saint-Maur-des-Fossés, France) were identified as factors interfering with the AO treatment with the HA + OCT device. In three patients without these risk factors, the treatment led to recovery within two or three days. The patient pretreated with Alveogyl and the smoker required six and seven applications of the HA + OCT device, respectively. According to these initial observations, it seems smoking and previous treatment with Alveogyl prolong the treatment of AO using the HA + OCT device that, in turn, shows a rapid effect if these risk factors are not present. Full article

(This article belongs to the Special Issue Hyaluronic Acid in Human Medicine)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Hyaluronic Acid in Human Medicine

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (12 papers)

Editorial

Research

Review

Other

Further Information

Guidelines

MDPI Initiatives

Follow MDPI