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Hyaluronic Acid: A Versatile Polysaccharide for Biomedical Applications 2023

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

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 23744

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Special Issue Editor

Dr. Laura Mayol

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Guest Editor

Department of Pharmacy, University of Naples “Federico II”, via Domenico Montesano 49, 80131 Napoli, Italy
Interests: biomaterial science and technology for drug delivery; regenerative medicine; tissue engineering
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Hyaluronic acid (HA), a naturally occurring anionic polysaccharide, has attracted significant research attention in the biomedical field because it possesses well-documented biocompatibility and pharmaceutical acceptability. Due to its strong hydrophilic character and its high molecular weight in biological tissues, it presents important structural and functional roles in the body. Its high molar mass is associated with its unique viscoelastic and rheological properties and predisposes HA to play important physiological roles in living organisms, making it an attractive biomaterial for various medical applications.

HA-based hydrogels have been designed to function as scaffolds for tissue engineering, for soft tissue augmentation, and drug delivery. Due to its multiple functional groups available for chemical conjugation, several HA–drug conjugates can be developed as macromolecular prodrugs. Additionally, amphiphilic HA derivatives can be synthesized by chemically grafting several hydrophobic moieties so as to produce HA-based micellar systems for the release of hydrophobic drugs. Since HA can also specifically bind CD44 and RHAMM receptors, which are overexpressed in many key forms of cancer, it has also been chemically anchored onto manifold drug-loaded micro- and nano-sized polymeric or liposomal particles.

This Special Issue aims to highlight the current progress in the field of HA-based biomaterials, by taking a multidisciplinary approach covering the expertise of the contributing authors in polymer science, pharmaceutical technology, bioconjugate chemistry, biology and medicine.

Dr. Laura Mayol
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
CD44 and RHAMM receptors
viscosupplementation
soft tissue augmentation
scaffolds for tissue engineering
nanoparticles
microparticles
micelles
liposomes
drug delivery systems
biomedicine

Published Papers (6 papers)

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Research

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13 pages, 3465 KiB

Open AccessArticle

Antibacterial Properties of Rose Bengal Conjugated to Hyaluronic Acid

by Melad Atrash, Iryna Hovor, Yanna Gurianov, Margarita Barel, Olga Semenova, Tamara Brider, Marina Nisnevitch and Faina Nakonechny

Int. J. Mol. Sci. 2024, 25(6), 3330; https://doi.org/10.3390/ijms25063330 - 15 Mar 2024

Viewed by 620

Abstract

Dental diseases, including conditions affecting oral structures, have become more common due to unhealthy lifestyle choices. Traditional antibiotic treatments face challenges related to the development of antibiotic resistance in bacteria. Photodynamic antibacterial chemotherapy is emerging as a promising alternative using photosensitizers to generate reactive oxygen species upon exposure to light. This article examines the photosensitizer Rose Bengal (RB) immobilized in hyaluronic acid (HA) for prolonged antibacterial action. The RB-HA conjugate demonstrated a molar ratio of approximately three RB residues to each of the ten units of HA. RB-HA exhibited a high singlet oxygen quantum yield (ΔΦ = 0.90), suggesting its efficacy in photodynamic treatment. A photostability analysis revealed slower photobleaching of RB-HA, which is essential for prolonged application. Under visible light and ultrasonic treatment, RB-HA exhibited effective antibacterial activity against Gram-positive S. aureus and Gram-negative E. coli bacteria for at least 80 days. The gradual release of RB ensured sustained bactericidal concentration. The study establishes RB-HA as a promising candidate for antimicrobial photodynamic and sonodynamic therapy in dental and other medical fields, providing enhanced stability and prolonged antibacterial efficacy. Full article

(This article belongs to the Special Issue Hyaluronic Acid: A Versatile Polysaccharide for Biomedical Applications 2023)

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14 pages, 3144 KiB

Open AccessArticle

Characterization of Hyaluronic Acid-Coated PLGA Nanoparticles by Surface-Enhanced Raman Spectroscopy

by Giuseppe La Verde, Antonio Sasso, Giulia Rusciano, Angela Capaccio, Sabato Fusco, Laura Mayol, Marco Biondi, Teresa Silvestri, Paolo A. Netti, Marco La Commara, Valeria Panzetta and Mariagabriella Pugliese

Int. J. Mol. Sci. 2023, 24(1), 601; https://doi.org/10.3390/ijms24010601 - 29 Dec 2022

Cited by 7 | Viewed by 2924

Abstract

Nanoparticles (NPs) coated with hyaluronic acid (HA) seem to be increasingly promising for targeted therapy due to HA chemical versatility, which allows them to bind drugs of different natures, and their affinity with the transmembrane receptor CD-44, overexpressed in tumor cells. However, an essential aspect for clinical use of NPs is formulation stability over time. For these reasons, analytical techniques capable of characterizing their physico-chemical properties are needed. In this work, poly(lactide-co-glycolide) (PLGA) NPs with an average diameter of 100–150 nm, coated with a few 10 s of nm of HA, were synthesized. For stability characterization, two complementary investigative techniques were used: Dynamic Light Scattering (DLS) and Surface-Enhanced Raman Scattering (SERS) spectroscopy. The first technique provided information on size, polidispersity index, and zeta-potential, and the second provided a deeper insight on the NP surface chemicals, allowing distinguishing of HA-coated NPs from uncoated ones. Furthermore, in order to estimate formulation stability over time, NPs were measured and monitored for two weeks. SERS results showed a progressive decrease in the signal associated with HA, which, however, is not detectable by the DLS measurements. Full article

(This article belongs to the Special Issue Hyaluronic Acid: A Versatile Polysaccharide for Biomedical Applications 2023)

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16 pages, 3077 KiB

Open AccessArticle

Impact of High-Molecular-Weight Hyaluronic Acid on Gene Expression in Rabbit Achilles Tenocytes In Vitro

by Iris Miescher, Petra Wolint, Christine Opelz, Jess G. Snedeker, Pietro Giovanoli, Maurizio Calcagni and Johanna Buschmann

Int. J. Mol. Sci. 2022, 23(14), 7926; https://doi.org/10.3390/ijms23147926 - 18 Jul 2022

Cited by 1 | Viewed by 1991

Abstract

(1) Background: Surgical tendon repair often leads to adhesion formation, leading to joint stiffness and a reduced range of motion. Tubular implants set around sutured tendons might help to reduce peritendinous adhesions. The lubricant hyaluronic acid (HA) is a viable option for optimizing such tubes with the goal of further enhancing the anti-adhesive effect. As the implant degrades over time and diffusion is presumed, the impact of HA on tendon cells is important to know. (2) Methods: A culture medium of rabbit Achilles tenocytes was supplemented with high-molecular-weight (HMW) HA and the growth curves of the cells were assessed. Additionally, after 3, 7 and 14 days, the gene expression of several markers was analyzed for matrix assembly, tendon differentiation, fibrosis, proliferation, matrix remodeling, pro-inflammation and resolution. (3) Results: The addition of HA decreased matrix marker genes, downregulated the fibrosis marker α-SMA for a short time and slightly increased the matrix-remodeling gene MMP-2. Of the pro-inflammatory marker genes, only IL-6 was significantly upregulated. IL-6 has to be kept in check, although IL-6 is also needed for a proper initial inflammation and efficient resolution. (4) Conclusions: The observed effects in vitro support the intended anti-adhesion effect and therefore, the use of HMW HA is promising as a biodegradable implant for tendon repair. Full article

(This article belongs to the Special Issue Hyaluronic Acid: A Versatile Polysaccharide for Biomedical Applications 2023)

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Review

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24 pages, 2878 KiB

Open AccessReview

Hyaluronic Acid Scaffolds for Loco-Regional Therapy in Nervous System Related Disorders

by Amel Djoudi, Rodolfo Molina-Peña, Natalia Ferreira, Ilaria Ottonelli, Giovanni Tosi, Emmanuel Garcion and Frank Boury

Int. J. Mol. Sci. 2022, 23(20), 12174; https://doi.org/10.3390/ijms232012174 - 12 Oct 2022

Cited by 7 | Viewed by 2345

Abstract

Hyaluronic acid (HA) is a Glycosaminoglycan made of disaccharide units containing N-acetyl-D-glucosamine and glucuronic acid. Its molecular mass can reach 10 MDa and its physiological properties depend on its polymeric property, polyelectrolyte feature and viscous nature. HA is a ubiquitous compound found in almost all biological tissues and fluids. So far, HA grades are produced by biotechnology processes, while in the human organism it is a major component of the extracellular matrix (ECM) in brain tissue, synovial fluid, vitreous humor, cartilage and skin. Indeed, HA is capable of forming hydrogels, polymer crosslinked networks that are very hygroscopic. Based on these considerations, we propose an overview of HA-based scaffolds developed for brain cancer treatment, central and peripheral nervous systems, discuss their relevance and identify the most successful developed systems. Full article

(This article belongs to the Special Issue Hyaluronic Acid: A Versatile Polysaccharide for Biomedical Applications 2023)

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19 pages, 977 KiB

Open AccessReview

The Rheology and Physicochemical Characteristics of Hyaluronic Acid Fillers: Their Clinical Implications

by Salvatore Piero Fundarò, Giovanni Salti, Dennis Malvin Hernandez Malgapo and Silvia Innocenti

Int. J. Mol. Sci. 2022, 23(18), 10518; https://doi.org/10.3390/ijms231810518 - 10 Sep 2022

Cited by 28 | Viewed by 10267

Abstract

Hyaluronic acid (HA) fillers have become the most popular material for facial volume augmentation and wrinkle correction. Several filler brands are currently on the market all around the world and their features are extremely variable; for this reason, most users are unaware of their differences. The study of filler rheology has become a wellspring of knowledge, differentiating HA fillers, although these properties are not described thoroughly by the manufacturers. The authors of this review describe the more useful rheological properties that can help clinicians understand filler characteristics and the likely correlation of these features with clinical outcomes. Full article

(This article belongs to the Special Issue Hyaluronic Acid: A Versatile Polysaccharide for Biomedical Applications 2023)

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20 pages, 2804 KiB

Open AccessReview

A Review on Current Strategies for Extraction and Purification of Hyaluronic Acid

by Carlos Dariel Rodriguez-Marquez, Susana Arteaga-Marin, Andrea Rivas-Sánchez, Renata Autrique-Hernández and Roberto Castro-Muñoz

Int. J. Mol. Sci. 2022, 23(11), 6038; https://doi.org/10.3390/ijms23116038 - 27 May 2022

Cited by 21 | Viewed by 4775

Abstract

Since it is known that hyaluronic acid contributes to soft tissue growth, elasticity, and scar reduction, different strategies of producing HA have been explored in order to satisfy the current demand of HA in pharmaceutical products and formulations. The current interest deals with production via bacterial and yeast fermentation and extraction from animal sources; however, the main challenge is the right extraction technique and strategy since the original sources (e.g., fermentation broth) represent a complex system containing a number of components and solutes, which complicates the achievement of high extraction rates and purity. This review sheds light on the main pathways for the production of HA, advantages, and disadvantages, along with the current efforts in extracting and purifying this high-added-value molecule from different sources. Particular emphasis has been placed on specific case studies attempting production and successful recovery. For such works, full details are given together with their relevant outcomes. Full article

(This article belongs to the Special Issue Hyaluronic Acid: A Versatile Polysaccharide for Biomedical Applications 2023)

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