Anti-Inflammatory and Pro-Regenerative Effects of Hyaluronan-Chitlac Mixture in Human Dermal Fibroblasts: A Skin Ageing Perspective

Donato, Alice; Belluzzi, Elisa; Mattiuzzo, Elena; Venerando, Rina; Cadamuro, Massimiliano; Ruggieri, Pietro; Vindigni, Vincenzo; Brun, Paola

doi:10.3390/polym14091817

Cited by 10 publications

(15 citation statements)

References 47 publications

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“…In particular, Gal-3 was recently associated with inflammation and ECM degradation in COPD [ 10 , 41 ]. Moreover, we recently demonstrated that the combination of HA and lactose-modified chitosan can prolong and improve the well-known anti-inflammatory activity of HA, attenuating macrophage-induced inflammation, MMP expression, and ROS production [ 17 , 42 ]. Macrophages are crucial regulatory cells of host defense and macrophage-induced inflammation contributes to the injury of bronchial tissues [ 4 , 10 , 12 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

The Anti-Inflammatory Effect of Lactose-Modified Hyaluronic Acid Molecules on Primary Bronchial Fibroblasts of Smokers

et al. 2023

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The progression of smoking-related diseases is characterized by macrophage-mediated inflammation, which is responsible for an increased expression of proinflammatory cytokines and galectins, molecules that bind specifically to β-galactoside sugars. This study aimed to assess the anti-inflammatory and antioxidant effects of a broad selection of differently lactose-modified hyaluronic acids (HA) named HYLACH®, which are able to bind proinflammatory galectins. The best HYLACH ligands for Gal-3 were selected in silico and their activities were tested in vitro on primary human bronchial fibroblasts obtained from smokers and inflamed with the conditioned medium of activated U937 monocytes. Changes in cell viability, ROS generation, proinflammatory mediators, and MMP expression, at both gene and protein levels, were analyzed. The in silico results show that HYLACH with a percentage of lactosylation of 10–40% are the best ligands for Gal-3. The in vitro study revealed that HYLACH compounds with 10, 20, and 40% lactosylation (HYLACH-1-2-3) administrated to inflamed cell cultures counteracted the oxidative damage and restored gene and protein expression for IL-1β, TNF-α, IL-6, Gal-1, Gal-3, and MMP-3 to near baseline values. The evidence that HYLACH attenuated macrophage-induced inflammation, inhibited MMP expression, and exhibited antioxidative effects provide an initial step toward the development of a therapeutic treatment suitable for smoking-related diseases.

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Section: Discussionmentioning

confidence: 99%

The Anti-Inflammatory Effect of Lactose-Modified Hyaluronic Acid Molecules on Primary Bronchial Fibroblasts of Smokers

et al. 2023

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“…The bioactive properties of CTL and its ability to induce cell aggregation , have been widely reported in the literature, both in vitro and in vivo . ,,,,,− …”

Section: Discussionmentioning

confidence: 99%

“…In this way, the expression of Gal-1-regulated genes is reduced, leading to a decrease in inflammation . Since CTL has been demonstrated to be able to inhibit the expression of galectin proteins both in vivo and in vitro , ,,, there is a growing interest in the use of this polymer for the production of materials to be used in the field of cartilage regeneration. , …”

Section: Introductionmentioning

confidence: 99%

Bioactive Lactose-Modified Chitosan Acts as a Temporary Extracellular Matrix for the Formation of Chondro-Aggregates

Pizzolitto

Scognamiglio

Baldini

et al. 2022

ACS Appl. Polym. Mater.

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Spheroids based on chondrocytes are gaining interest in the treatment of injured cartilage tissue due to their regenerative potential. In this study, chondrocyte-based aggregates were formed by culturing cells on a polymeric coating of a lactose-modified chitosan (CTL) and their evolution was followed for 14 days of culture. Morphological analyses through scanning electron microscopy indicated that these cell aggregates formed by a process of cell aggregation rather than proliferation, resulting in structures with an irregular morphology that were up to 1 mm in size. Chondrocytes interact very closely with CTL. In the early days of cellular aggregation, CTL is distributed among the cells, while in later stages, it is localized in the inner part of the aggregates, forming an amorphous matrix. The initial outer position of the polymer is replaced over time by an increased matrix deposition whose main component is type II collagen. Transmission electron microscopy pointed out that the chondrocytes internalized the polymer during the first days of culture. The presence of CTL does not affect the ability of cells to migrate from chondro-aggregates when transferred to uncoated wells, mimicking the ability of cells to colonize a cartilage defect. Overall, these results suggest that CTL plays a role as a temporary matrix for chondrocytes aggregation during chondro-aggregates formation. This opens up innovative therapeutic approaches for cartilage regeneration without the need to use a scaffold to deliver cells to the damaged site.

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“…25 This allows the formation of an ammonium salt of DMTMM which reacts, by a substitution mechanism, with the carboxylic group of HA to form the active triazine-ester followed by a nucleophilic attack of LAC-NH 2 . 7 To synthesize samples with different DS values in a range considered ideal according to previous biological evaluation, 8 various reaction parameters, such as stoichiometry of the triazine condenser (DMTMM) and LAC-NH 2, and pH, were optimized.…”

Section: Hylach ® Synthesismentioning

confidence: 99%

“…Interaction studies were performed on saccharide ligands and OHA and HYLACH ® (OHY1 and OHY2), obtained by enzymatical hydrolysis. OHY1 and OHY2 were selected due to the similarity of molecular weight and DS with HYLACH 1 and HYLACH 3, respectively, cited by Donato et al 8 ITC results showed that the interactions between Gal-3 and saccharide ligands, OHA and OHY are all energetically favorable binding reactions (ΔG negative) and entropically driven (TΔS > 0), except for OHY2. For small ligands (LAC-NH 2 , galactose, and lactose) the stoichiometry of the interaction (N) is in the order of 1 protein:1 ligand, and the dissociation constant (K D ) is the order of µM, with values similar to data reported for lactose.…”

Section: Isothermal Titration Microcalorimetrymentioning

confidence: 99%

A novel biomimetic probe for galectin‐3 recognition: Chemical synthesis and structural characterization of a β‐galactose branched sodium hyaluronate

Nizzolo,

Esposito,

et al. 2024

Proteoglycan Research

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Sodium hyaluronate (HA), a derivative of hyaluronan, is a natural and biocompatible polysaccharide that interacts with cluster of differentiation‐44 receptor to promote fine‐tuning of inflammation, fibrosis, and tissue remodeling. HA has a smaller molecular weight than hyaluronan and is overall more stable being less prone to oxidation. In this study, we report a novel lactose‐functionalized sodium hyaluronate, named HYLACH®. Functionalization with multiple β‐galactose residues facilitates its interaction with galectin‐3, a β‐galactose binding lectin implicated in various pathological processes including inflammation, host defense, and fibrosis, especially critical in idiopathic pulmonary fibrosis (IPF). Our strategy was to modify HA, to varying extents, at carboxyl sites with 1‐amino‐1‐deoxy‐lactitol, in the presence of 4‐(4,6‐dimethoxy‐1,3,5‐triazin‐2‐yl)‐4‐methyl morpholinium chloride in aqueous media. We characterized the chemical structure, molecular weight, and degree of substitution of HYLACH® using NMR spectroscopy and size exclusion chromatography. We further determined several key parameters including its stability toward enzymatic degradation and the binding affinity and conformational changes of galectin‐3 interaction with HYLACH®. Collectively, the generation of a novel functionalized HA with an ability to bind and suppress galectin‐3 function, in combination with safety and biocompatibility, offers the opportunity to test this compound in therapeutic trials of devastating fibrotic diseases such as IPF.

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Anti-Inflammatory and Pro-Regenerative Effects of Hyaluronan-Chitlac Mixture in Human Dermal Fibroblasts: A Skin Ageing Perspective

Cited by 10 publications

References 47 publications

The Anti-Inflammatory Effect of Lactose-Modified Hyaluronic Acid Molecules on Primary Bronchial Fibroblasts of Smokers

The Anti-Inflammatory Effect of Lactose-Modified Hyaluronic Acid Molecules on Primary Bronchial Fibroblasts of Smokers

Bioactive Lactose-Modified Chitosan Acts as a Temporary Extracellular Matrix for the Formation of Chondro-Aggregates

A novel biomimetic probe for galectin‐3 recognition: Chemical synthesis and structural characterization of a β‐galactose branched sodium hyaluronate

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