Search Results (98)

Despite extensive research on fascial mechanobiology, no unified mechanotransduction framework has been established to explain how mechanical forces translate into adaptive cellular responses in fascial tissue. This narrative review synthesizes evidence from mesenchymal cell and fibroblast research to propose the Ca²⁺–Hyaluronan (CHA) axis as a comprehensive mechanotransduction feedback loop for fascia phenomenology. The CHA framework describes how mechanical stress activates Ca²⁺ channels (Piezo1, TRPV4, P2Y2), triggering HAS2-mediated hyaluronan (HA) synthesis. The molecular weight of synthesized HA then determines receptor signaling outcomes: high-molecular-weight HA binds CD44 to promote tissue stability and quiescence, while low-molecular-weight HA fragments activate RHAMM to drive remodeling and repair—a dynamic oscillation termed “Quiet or Riot.” Three key conclusions emerge: First, the CHA framework is well supported by existing literature on mesenchymal cells, providing a testable model for fascial mechanobiology. Second, HA molecular weight dynamics and CD44/RHAMM oscillation have direct implications for optimizing movement, manual therapy, and rehabilitative interventions. Third, while HA-CD44/RHAMM signaling is broadly implicated in tissue remodeling, Ca²⁺-dependent regulatory mechanisms specific to fasciacytes require experimental validation. A critical translational gap remains: the absence of quantitative mechanical thresholds distinguishing beneficial from pathological loading limits clinical application. Future research should employ 3D matrix models, live imaging, receptor manipulation, and omics profiling to establish these thresholds and validate the CHA framework in fasciacytes. Understanding fascial mechanotransduction through the CHA loop may transform approaches to movement prescription, manual therapy, and treatment of fascial dysfunction. Full article

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a small neuropeptide detected first in the hypothalamo–hypophyseal system; recently, it has also been identified in peripheral organs and in tumours. It is well demonstrated that PACAP exerts cell- and tissue-protecting effects in various stressful conditions and helps to maintain tissue homeostasis. In melanoma, the anti-invasive effect of PACAP has been demonstrated; however, there is also existing sporadic data which proves PACAP plays a role in melanoma progression. The major goal of our study was to investigate the signalling targets of PACAP in A2058 and WM35 melanoma cell lines in vitro. Various molecular players of melanocyte differentiation and function responded to PACAP application. SOX9 expression increased while SOX10 expression decreased and CREB signalling did not change. The expression level of TYRP1 decreased, while DCT elevated, and MITF expression showed changes at the mRNA level and in its subcellular localisation. In contrast, the amount of hyaluronan (HA) and expressions of its synthases, as well as RHAMM, increased, indicating the role of PACAP in secretion of an HA-rich matrix. In parallel with these results, we detected elevated hyaluronidase2 (Hyal2) expression in the presence of PACAP. On the other hand, alfaV and beta3 integrin expressions did not alter significantly. Our results demonstrate that exogenous PACAP modulates the expression of multiple target molecules in melanoma cells. Some of the significantly responding molecules take part in hyaluronan homeostasis, suggesting an effect of PACAP on tumour matrix composition, through which it can modulate invasiveness of melanoma cells. Full article

Hyaluronic acid (HA) is a ubiquitous glycosaminoglycan essential for maintaining tissue hydration, structural integrity, and immunological homeostasis in vertebrates. Although traditionally regarded as a host-derived molecule, HA is also produced by a range of microorganisms, most notably Streptococcus spp., through specialized hyaluronan synthases (HAS). Microbial HA and host-derived HA fragments play key roles not only in tissue physiology but also in infection biology, influencing microbial virulence, biofilm formation, and immune evasion. In bacteria, HA-rich capsules promote adhesion, shield pathogens from complement-mediated opsonization and phagocytosis, and facilitate dissemination through host tissues. Conversely, HA-degrading enzymes and reactive oxygen species generate low-molecular-weight HA fragments that amplify inflammation by activating—toll-like receptor 2 (TLR2)/toll-like receptor 4 (TLR4) signaling, contributing to chronic inflammatory states. Furthermore, microbial HA modulates biofilm organization in both bacterial and fungal pathogens, enhancing persistence and antimicrobial tolerance. Clinically, widespread use of HA-based dermal fillers has generated increasing concern over delayed biofilm-associated infections, diagnostic challenges, and complications arising from microbial contamination and host–microbe interactions. Recent advances in HA engineering, including anti-microbial HA conjugates and receptor-targeted biomaterials, offer promising strategies to mitigate infection risk while expanding therapeutic applications. This review synthesizes current knowledge on HA biosynthesis across biological kingdoms, its dualistic role in health and disease, and its emerging relevance at the interface of microbiology, immunology, and biomedical applications. Full article

Background: Hyaluronan, or hyaluronic acid (HA), is a glycosaminoglycan with structural and signaling functions playing key roles in human skin homeostasis. It ensures hydration and biomechanical properties of this tissue as well as regulates cell adhesion, migration, proliferation, and inflammation. Its biocompatibility, viscoelastic properties, biological functions, and large-scale sustainable bioproduction made this polysaccharide a hero molecule of the cosmetic industry. Methods: A literature search was conducted to discuss the skin and hair benefits of the external use of HA and its derivatives. Four main questions were addressed: What are the different forms of HA in cosmetic formulations? What about their safety? Does HA penetrate human skin and hair? What are the benefits and mode of actions of HA, and its derivatives, in the fields of cosmetic and dermatology? Results: The analysis revealed HA below 100 kDa to penetrate skin, and lower molecular weight being able to reach the dermis. The safety of HA-containing formulations has been evaluated in several clinical trials and is supported by independent reports of commercial ingredients. We described HA molecules having beneficial effects on skin and hair, as well as their mode of action. Conclusions: This review provides comprehensive information on the nature and efficacy of topical HA, and its derivatives, in cosmetic applications, with an emphasis on hair care. New areas of research were highlighted as the vectorization of high-molecular-weight HA. Full article

Background: The binding of glycosaminoglycans (GAG) to Wnt signaling components plays a key regulatory role in bone formation and regeneration. We previously reported de novo designed chemically modified hyaluronan derivatives, named _REGAG (Rationally Engineered GAG), which demonstrated bone-regenerative properties in a mouse calvaria defect model. To gain initial insights into the pharmacological profile of two _REGAG currently under preclinical investigation in mice, we performed a comprehensive in silico investigation of their binding to human and murine serum albumin (HSA and MSA), as it might influence their ADME properties. Furthermore, we evaluated whether _REGAG binding might impact the recognition of well-characterized HSA-binding drugs. Methods: State-of-the-art in silico ADMET tools, docking and molecular dynamics simulations were used to predict and characterize the interaction of _REGAG with HSA and MSA, and to investigate the molecular mechanisms involved at the atomic level. Results: The investigated _REGAG molecules show a consistent binding preference for the FA1 site in both proteins, and an additional preference for the FA7 site in HSA. Their recognition might induce protein conformational changes and alter the functional state. Furthermore, _REGAG’s conformational adaptability is predicted to influence their binding to the FA5/6 and FA8/9 sites of HSA, and to the FA3/4 and FA7 sites of MSA. Conclusions: Our investigations predict the binding of two hyaluronan derivatives to HSA and MSA. The mechanistic insights gained into the molecular recognition of these two _REGAG molecules offer valuable information for their potential clinical application and serve as a rational basis for future molecular design aimed at improving pharmacokinetic properties. Full article

Glycosaminoglycans (GAGs) are essential regulators of numerous biological processes through their interactions with growth factors, chemokines, cytokines, and enzymes. Their structural diversity and heterogeneity, however, limit reproducibility and translational use, as native GAGs are typically obtained from animal-derived sources with notable batch-to-batch variability. To overcome these challenges, a wide range of GAG mimetics has been developed with the aim of replicating or modulating the biological functions of native GAGs while offering improved structural definition, accessibility, and therapeutic potential. Polysaccharide-based GAG mimetics, including derivatives of heparan sulfate, hyaluronan, dextran, and other natural glycans, represent one major strategy, whereas non-saccharide-based mimetics provide alternative scaffolds with enhanced stability and selectivity. Both approaches have yielded compounds that serve as valuable tools for dissecting GAG/protein interactions and as candidates for therapeutic development. Biomedical applications of GAG mimetics span diverse areas such as cancer, cardiovascular and inflammatory diseases, bone and cartilage regeneration, wound healing, and infectious diseases. This mini-review summarizes key developments in the design and synthesis of GAG mimetics, highlights their potential biomedical applications, and discusses current challenges and future perspectives in advancing them toward clinical translation. Full article

This paper proposes hybrid hydrogel insulin carriers based on alginate-hyaluronan (ALG/HA) and hydroxypropyl methylcellulose-hyaluronan (HPMC/HA) for topical application. The inclusion of insulin in a modern dressing can help restore metabolic balance and proper cell signaling in diseased tissue. Preformulation studies of the developed preparations were conducted, including analysis of the in vitro pharmaceutical availability of insulin, rotational and oscillatory rheology tests, and texture profile analysis. It was found that the developed insulin formulations provide an acceptable compromise between rheological and textural properties and ease of application, while ensuring prolonged release of the active substance. The results obtained provide a basis for further preclinical and clinical studies. Full article

Hyaluronan (HA), a high-molecular-weight polysaccharide naturally found in vertebrate tissues such as skin, joints, and the vitreous body, plays a critical role in various biological processes. Its functionality is highly dependent on molecular weight, with high-molecular-weight HA exhibiting anti-inflammatory and immunosuppressive effects, while low-molecular-weight HA promotes inflammation, immunostimulation, and angiogenesis. Due to its biocompatibility, biodegradability, and tunable properties, HA has gained increasing attention in biomedical applications. This review summarizes recent advances in the encapsulation of HA with other polymers and therapeutic agents in nanosystems, particularly hydrogels and nanoparticles. HA-based formulations demonstrate improved therapeutic outcomes, including drug release sustained up to 7 days, wound closure rates exceeding 90% in animal models, particle size in the range of 50–300 nm, and enhanced bioavailability of encapsulated drugs by 2–3 fold compared with free drugs. Such properties have shown promise in enhancing therapeutic efficacy and targeted drug delivery in the treatment of skin wound healing, diabetes, osteoarthritis, rheumatoid arthritis, and ophthalmic diseases. The review emphasizes how HA’s modifications and composite systems optimize drug release profiles and biological interactions, thereby contributing to the development of next-generation biomedical therapies. Full article

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

Bassia scoparia (Syn. Kochia scoparia (L.) Schrad.) is a medicinal plant whose fruit, Kochiae Fructus, has been extensively studied for its dermatological applications. This study focused on extracts from the whole plant B. scoparia (WPBS), excluding fruits, to address the research gap regarding the medicinal properties of non-fruit parts. The diverse skin benefits of WPBS, including its anti-photoaging, moisturizing, wound healing, anti-inflammatory, and anti-angiogenic effects, were investigated. The WPBS extract enhanced the viability of keratinocytes (HaCaT) without inducing cytotoxic effects. WPBS significantly reduced matrix metalloproteinase-1 (MMP-1) levels and increased collagen type I alpha 1 (COL1A1) levels (p < 0.01) in fibroblasts exposed to ultraviolet B (UVB) radiation, indicating strong anti-photoaging effects. WPBS upregulated skin hydration markers such as aquaporin-3 (AQP3) and hyaluronan synthase-3 (HAS3) and effectively accelerated fibroblast wound closure compared to the positive control. Furthermore, WPBS substantially downregulated the expression of inflammatory (COX-2 and IL-1β) and angiogenic markers (VEGF). Transcriptome analysis (RNA-seq) confirmed that WPBS suppressed inflammation-related and UV-induced gene expression pathways. Overall, these findings expand the therapeutic scope of B. scoparia beyond its traditional fruit use and suggest that WPBS is a promising botanical ingredient for various skin applications. Full article

This study presents a detailed Raman spectroscopic investigation of hydrogels composed of sodium hyaluronate and two N-terminally blocked dipeptides: N-acetyl-L-alanine-methyl-amide (NAcAlaNHMA) and N-acetyl-L-tyrosine-methyl-amide (NAcTyrNHMA). Vibrational spectra of the dipeptides in both crystalline and aqueous forms were analyzed and supported by density functional theory (DFT) calculations. Spectral features of the hyaluronan component were elucidated by simulating the vibrational modes of its two principal disaccharide building blocks. Gels were prepared with varying dipeptide-to-hyaluronan ratios, and their structural characteristics were examined using Raman spectroscopy and atomic force microscopy. The results showed that while NAcAlaNHMA exhibited no significant interaction with the HA matrix, NAcTyrNHMA demonstrated specific binding behavior, as evidenced by notable shifts in its N–H and C–O–H vibrational bands. These findings indicate that NAcTyrNHMA binds to hyaluronic acid via hydrogen bonding, likely involving carboxyl and hydroxyl functional groups. This study highlights the potential for selective tuning of HA-based hydrogels using dipeptides, with implications for biomedical applications such as drug delivery, antimicrobial gels and biomaterial design. Full article

Nanogels are polymer-based, crosslinked hydrogel particles on the nanometer scale. Nanogels developed from synthetic and natural polymers have gathered a great deal of attention in industry and scientific society due to having an increased surface area, softness, flexibility, absorption, and drug loading ability, as well as their mimicking the environment of a tissue. Nanogels having biocompatibility, nontoxic and biodegradable properties with exceptional design, fabrication, and coating facilities may be used for a variety of different biomedical applications, such as drug delivery and therapy, tissue engineering, and bioimaging. Nanogels fabricated by chemical crosslinking and physical self-assembly displayed the ability to encapsulate therapeutics, including hydrophobic, hydrophilic, and small molecules, proteins, peptides, RNA and DNA sequences, and even ultrasmall nanoparticles within their three-dimensional polymer networks. One of the many drug delivery methods being investigated as a practical option for targeted delivery of drugs for cancer treatment is nanogels. The delivery of DNA and anticancer drugs like doxorubicin, epirubicin, and paclitaxel has been eased by polymeric nanogels. Stimuli-responsive PEGylated nanogels have been reported as smart nanomedicines for cancer diagnostics and therapy. Another promising biomedical application of nanogels is wound healing. Wounds are injuries to living tissue caused by a cut, blow, or other impact. There are numerous nanogels having different polymer compositions that have been reported to enhance the wound healing process, such as hyaluronan, poly-L-lysine, and berberine. When antimicrobial resistance is present, wound healing becomes a complicated process. Researchers are looking for novel alternative approaches, as foreign microorganisms in wounds are becoming resistant to antibiotics. Silver nanogels have been reported as a popular antimicrobial choice, as silver has been used as an antimicrobial throughout a prolonged period. Lignin-incorporated nanogels and lidocaine nanogels have also been reported as an antioxidant wound-dressing material that can aid in wound healing. In this review, we will summarize recent progress in biomedical applications for various nanogels, with a prime focus on cancer and wound healing. Full article

Hyaluronic acid (or hyaluronan) is a polysaccharide with therapeutic applications in dentistry due to its lubricating, anti-inflammatory, and antibacterial properties. This study evaluates the diffusion, conductivity, and viscosity of the sodium salt of HyH (that is, NaHy) with different molecular weights (124 kDa, 245 kDa, and 1800 kDa) in artificial saliva at pH 2.3, 4, 5, 6.8, and 8. Using the Taylor dispersion technique at 298.15 K, diffusion coefficients were determined and analyzed based on Fick’s second law equation. Results showed that NaHy diffusion was higher at acidic pH, particularly at pH 2.3, and decreased at pH 8, likely due to structural compaction in acidic conditions and expansion in alkaline media. The higher molecular weight of this polysaccharide exhibited greater diffusion and conductivity, suggesting an extended conformation that enhances mobility. These findings indicate that both pH and molecular weight significantly influence NaHy transport properties. Optimizing these parameters may enhance HA’s bioavailability and effectiveness in topical oral applications, improving its therapeutic potential in treating periodontal and oral conditions. Full article

Jatrorrhizine is one of the major bioactive compounds found in Phellodendron amurense. Previous studies have reported various health benefits of jatrorrhizine, but little is known about its effect on skin health. In this study, jatrorrhizine isolated from Phellodendron amurense was used to determine the impact on collagen homeostasis in CCD-986sk human dermal fibroblast cells. Jatrorrhizine did not show toxicity of up to 10 μM in CCD-986sk cells. Jatrorrhizine induced procollagen and hyaluronic acid synthesis by increasing the gene expression of collagen type I alpha 2, TIMP metallopeptidase inhibitor 1, transforming growth factor beta 1, and hyaluronan synthase 2. In addition, jatrorrhizine treatment inhibited the gene expression of matrix metallopeptidase 1 and matrix metallopeptidase 9 by increasing tissue inhibitors of metalloproteinase. Our results suggest that jatrorrhizine has the potential for application in therapeutic and cosmetic products to improve collagen homeostasis and prevent wrinkle formation. Full article

Hyaluronan (HA) levels are dynamically regulated homeostatically through biosynthesis and degradation. HA homeostasis is often perturbed under disease conditions. HA degradation products are thought to contribute to disease pathology. The hyaluronidase CEMIP requires the presence of living cells for its HA depolymerizing activity. CEMIP is overexpressed in a variety of pathological conditions, and the inhibition of its hyaluronidase activity therefore has therapeutic potential. To identify novel inhibitors of the CEMIP hyaluronidase activity, we established here a cell-compatible, medium-throughput assay for CEMIP-dependent HA depolymerization. The assay employs ultrafiltration plates to separate low- from high-molecular-weight HA, followed by quantification of HA fragments using an HA ELISA-like assay. Using this assay, we tested a range of compounds that have been reported to inhibit other hyaluronidases. Thereby, we identified several sulfated hydrocarbon polymers that inhibit CEMIP more potently than other hyaluronidases. One of these is heparin, a sulfated glycosaminoglycan produced by mast cells that constitutes the first described physiological CEMIP inhibitor. The most potent inhibitor (IC₅₀ of 1.8 nM) is dextran sulfate, a synthetic sulfated polysaccharide. Heparin and dextran sulfate are used in numerous established and experimental biomedical applications. Their ability to inhibit CEMIP needs to be taken into account in these contexts. Full article