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New Insights into Hyaluronan in Human Medicine

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

Deadline for manuscript submissions: 30 January 2026 | Viewed by 1285

Special Issue Editor


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Guest Editor
Institute for Biomedical Research and Innovation-National Research Council (IRIB-CNR), Via Ugo la Malfa 153, 90146 Palermo, Italy
Interests: cellular biology, particularly on understanding the molecular mechanisms involved in cell-cell and cell-matrix interactions, as well as the release of extracellular vesicles; exploring above processes within the context of regenerative medicine, with a specific focus on diabetes

Special Issue Information

Dear Colleagues,

Hyaluronan (HA) plays a multifaceted role in various physiological and pathological processes, including the regulation of cell growth, migration, and survival. The biological activities of HA are influenced by its molecular mass, turnover rate, and interactions with specific receptors, yet the precise mechanisms through which HA orchestrates these functions remain partially unclear. Recent metabolomics studies have uncovered novel roles for HA in cellular metabolism, highlighting its ability to modulate cellular behavior by reprogramming metabolism in response to HA production. Notably, HA overproduction in adipose tissue has been associated with improved glucose metabolism, suggesting the complex roles played by HA in metabolic diseases such as obesity and type 2 diabetes. Additionally, HA degradation has been linked to tumor cell migration and glucose uptake. This Special Issue aims to explore the diverse roles of HA in various diseases, providing new insights into its complex biological functions and potential use of HA in therapeutic applications and clinical practice.

Dr. Monica Salamone
Guest Editor

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Keywords

  • hyaluronan
  • regenerative medicine
  • inflammation
  • cancer therapy
  • metabolomics 
  • hyaluronidases
  • cell–matrix interaction
  • glucose metabolism
  • pathological processes

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Published Papers (2 papers)

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Research

12 pages, 1664 KB  
Article
Dual Effect of 4-Methylumbelliferone on INS1E Cells: Enhancing Migration and Glucose-Stimulated Insulin Secretion
by Giorgia Adamo, Daniele Romancino, Paola Gargano, Marta Sarullo, Aldo Nicosia, Sabrina Picciotto, Giulia Smeraldi, Antonella Bongiovanni and Monica Salamone
Int. J. Mol. Sci. 2025, 26(15), 7637; https://doi.org/10.3390/ijms26157637 - 7 Aug 2025
Viewed by 420
Abstract
Recent studies have demonstrated that the coumarin derivative 4-Methylumbelliferone (4MU) has an antidiabetic effect in rodent models. 4MU is known to decrease the availability of hyaluronan (HA) substrates and inhibit the activity of different HA synthases. Nevertheless, it has been observed that 4MU [...] Read more.
Recent studies have demonstrated that the coumarin derivative 4-Methylumbelliferone (4MU) has an antidiabetic effect in rodent models. 4MU is known to decrease the availability of hyaluronan (HA) substrates and inhibit the activity of different HA synthases. Nevertheless, it has been observed that 4MU may also affect cellular metabolism. In this study, we utilize the rat insulinoma beta cell line (INS-1E) cultured in both two-dimensional (2D) and three-dimensional (3D) experimental settings (pseudo islets), as an in vitro model to study beta cell functionality. For the first time, we observed that treating INS1E cells with 4MU results in improved insulin secretion. Additionally, we discovered that 4MU treatment elicited morphological changes from multilayer to monolayer conditions, along with a varied distribution of insulin granules and cell adhesion properties. Notably, we found that insulin secretion is not correlated with HA production. The same result was observed in co-culture experiments involving INS-1E cells and stromal vascular fraction (SVF) from adipose tissue. These experiments aim to investigate the effects of 4MU on beta cells in the context of its potential use in early-stage type 1 diabetes and in enhancing islet transplantation outcomes. Full article
(This article belongs to the Special Issue New Insights into Hyaluronan in Human Medicine)
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29 pages, 3563 KB  
Article
Assessment of Hydrogels for Intra-Articulate Application, Based on Sodium Hyaluronate Doped with Synthetic Polymers and Incorporated with Diclofenac Sodium
by Dorota Wójcik-Pastuszka, Maja Grabara and Witold Musiał
Int. J. Mol. Sci. 2025, 26(15), 7631; https://doi.org/10.3390/ijms26157631 - 6 Aug 2025
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Abstract
The intra-articular application of drugs has gained considerable interest with regard to formulations for advanced drug delivery systems. It has been identified as a potential route for local drug delivery. A drug agent is usually incorporated into the hydrogel to prolong and control [...] Read more.
The intra-articular application of drugs has gained considerable interest with regard to formulations for advanced drug delivery systems. It has been identified as a potential route for local drug delivery. A drug agent is usually incorporated into the hydrogel to prolong and control the drug release. This study aimed to design and evaluate an intra-articular hydrogel based sodium hyaluronate, which was modified with an additional polymer to enable the sustained release of the incorporated anti-inflammatory agent, diclofenac sodium (NaDic). Viscosity studies, drug release tests and FTIR−ATR measurements, as well as DSC analysis, were carried out to evaluate the obtained formulations. The viscosity measurements were performed using a rotational viscometer. The drug release was carried out by employing the apparatus paddle over the disk. The concentration of the released drug was obtained spectrophotometrically. The results revealed that the addition of the second polymer to the matrix influenced the dynamic viscosity of the hydrogels. The highest viscosity of (25.33 ± 0.55) × 103 cP was observed when polyacrylic acid (PA) was doped in the formulation. This was due to the hydrogen bond formation between both polymers. The FTIR−ATR investigations and DSC study revealed the hydrogen bond formation between the drug and both polymers. The drug was released the slowest from hydrogel doped with PA and 17.2 ± 3.7% of NaDic was transported to the acceptor fluid within 8 h. The hydrogel based on hyaluronan sodium doped with PA and containing NaDic is a promising formulation for the prolonged and controlled intra-articulate drug delivery of anti-inflammatory agents. Full article
(This article belongs to the Special Issue New Insights into Hyaluronan in Human Medicine)
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