Non-sulfated Glycosaminoglycan Research Articles

A Critical Sojourn of Hyaluronic Acid-based Hydrogels in the Wound Healing Process: Current Advances and Future Prospects

Abstract: "Hyaluronic acid (HA), a non-sulfated glycosaminoglycan (GAG), is a significant component of the epidermal extracellular matrix (ECM). It plays multiple roles in the inflammatory response, cell adhesion, migration, proliferation, differentiation, angiogenesis, and tissue regeneration. Due to its inherent characteristics, including non-immunoreactivity, exceptional biocompatibility, biodegradability, native biofunctionality, hydrophilicity, and non-immunoreactivity, HA has found applications in the production of wound dressings. HA's synergistic role in enhancing deeper penetration into chronic wounds and its biofunctional properties in the healing process have been harnessed. HA-based wound dressings, often incorporating biomolecules or drugs to improve the dressing's biochemical performance during wound healing, have been developed. In this review, we explore the current state of knowledge regarding hydrogels based on HA, focusing on their biofunctional properties and delivery mechanisms. We present the latest developments in the research and development of HA-based hydrogels for the treatment of skin wounds."

Elevated RHAMM as a biomarker for predicting diabetic kidney disease in patients with type 2 diabetes.

Diabetic kidney disease (DKD) poses a significant challenge globally as a complication of diabetes. Hyaluronan (HA), a critical non-sulfated glycosaminoglycan in the extracellular matrix, plays a pivotal role in the progression of DKD. This study assesses the predictive significance of HA's corresponding receptor, RHAMM (receptor for HA-mediated motility), in DKD pathogenesis in type 2 diabetes (T2DM) patients. Enzyme-linked immunosorbent assays were utilized to measure plasma and urine levels of HA, CD44 and RHAMM in 99 diabetic patients. Immunohistochemistry staining was employed to examine HA deposition, CD44 and RHAMM expressions from 18 biopsy-proven DKD patients. Spearman correlation analysis, linear regression and receiver operating characteristic (ROC) analysis were conducted to establish associations between plasma HA, CD44 and RHAMM levels, and clinical parameters in DKD patients with T2DM. Elevated plasma and urine HA, CD44 and RHAMM levels were notably observed in the severe renal dysfunction group. Plasma RHAMM exhibited positive correlations with HA (r=0.616, P<.001) and CD44 (r=0.220, P<.001), and a negative correlation with estimated glomerular filtration rate (eGFR) (r=-0.618, P<.001). After adjusting for other potential predictors, plasma RHAMM emerged as an independent predictor of declining eGFR (β=-0.160, P<.05). Increased HA, CD44 and RHAMM levels in kidney biopsies of DKD patients were closely associated with heightened kidney injury. The ROC curve analysis highlighted an area under the curve (AUC) of 0.876 for plasma RHAMM, indicating superior diagnostic efficacy compared to CD44 in predicting DKD pathogenesis. The combined AUC of 0.968 for plasma RHAMM, HA and CD44 also suggested even greater diagnostic potential for DKD pathogenesis. These findings provide initial evidence that elevated RHAMM levels predict DKD pathogenesis in T2DM patients. The formation of a triple complex involving HA, CD44 and RHAMM on the cell surface shows promise as a targetable biomarker for early intervention to mitigate severe renal dysfunctions.

Chemical Modifications in Hyaluronic Acid-Based Electrospun Scaffolds.

Hyaluronic acid (HA) is a natural, non-sulfated glycosaminoglycan (GAG) present in ECM. It is involved in different biological functions with appealing properties in cosmetics and pharmaceutical preparations as well as in tissue engineering. Generally, HA has been electrospun in blends with natural or synthetic polymers to produce fibers having diameters in the order of nano and micro-scale whose pores can host cells able to regenerate damaged tissues. In the last decade, a rich literature on electrospun HA-based materials arose. Chemical modifications were generally introduced in HA scaffolds to favour crosslinking or conjugation with bioactive molecules. Considering the high solubility of HA in water, HA-based electrospun scaffolds are cross-linked to increase the stability in biological fluids. Crosslinking is necessary also to avoid the release of HA from the hybrid scaffold when implanted in-vivo. Furthermore, to endow the HA based scaffolds with new chemical or biological properties, conjugation of bioactive molecules to HA was widely reported. Herein, we review the existing research classifying chemical modifications on HA and HA-based electrospun fibers into three categories: i) in-situ crosslinking of electrospun HA-based scaffolds ii) off-site crosslinking of electrospun HA-based scaffolds; iii) conjugation of biofunctional molecules to HA with focus on peptides.

Nanotechnological Research for Regenerative Medicine: The Role of Hyaluronic Acid.

Hyaluronic acid (HA) is a linear, anionic, non-sulfated glycosaminoglycan occurring in almost all body tissues and fluids of vertebrates including humans. It is a main component of the extracellular matrix and, thanks to its high water-holding capacity, plays a major role in tissue hydration and osmotic pressure maintenance, but it is also involved in cell proliferation, differentiation and migration, inflammation, immunomodulation, and angiogenesis. Based on multiple physiological effects on tissue repair and reconstruction processes, HA has found extensive application in regenerative medicine. In recent years, nanotechnological research has been applied to HA in order to improve its regenerative potential, developing nanomedical formulations containing HA as the main component of multifunctional hydrogels systems, or as core component or coating/functionalizing element of nanoconstructs. This review offers an overview of the various uses of HA in regenerative medicine aimed at designing innovative nanostructured devices to be applied in various fields such as orthopedics, dermatology, and neurology.

Hyaluronan: Sources, Structure, Features and Applications.

Hyaluronan (HA) is a non-sulfated glycosaminoglycan that is present in a variety of body tissues and organs. Hyaluronan has a wide range of biological activities that are frequently influenced by molar mass; however, they also depend greatly on the source, purity, and kind of impurities in hyaluronan. High-molar-mass HA has anti-inflammatory, immunosuppressive, and antiangiogenic properties, while low-molar-mass HA has opposite properties. A number of chemical modifications have been performed to enhance the stability of HA and its applications in medical practice. Hyaluronan is widely applied in medicine, such as viscosupplementation, ophthalmology, otolaryngology, wound healing, cosmetics, and drug delivery. In this review, we summarized several medical applications of polymers based on the hyaluronan backbone.

Chondroitin sulfate, dermatan sulfate, and hyaluronic acid differentially modify the biophysical properties of collagen-based hydrogels

Fibrillar collagens and glycosaminoglycans (GAGs) are structural biomolecules that are natively abundant to the extracellular matrix (ECM). Prior studies have quantified the effects of GAGs on the bulk mechanical properties of the ECM. However, there remains a lack of experimental studies on how GAGs alter other biophysical properties of the ECM, including ones that operate at the length scales of individual cells such as mass transport efficiency and matrix microstructure. This study focuses on the GAG molecules chondroitin sulfate (CS), dermatan sulfate (DS), and hyaluronic acid (HA). CS and DS are stereoisomers while HA is the only non-sulfated GAG. We characterized and decoupled the effects of these GAG molecules on the stiffness, transport, and matrix microarchitecture properties of type I collagen hydrogels using mechanical indentation testing, microfluidics, and confocal reflectance imaging, respectively. We complement these biophysical measurements with turbidity assays to profile collagen aggregate formation. Surprisingly, only HA enhanced the ECM indentation modulus, while all three GAGs had no effect on hydraulic permeability. Strikingly, we show that CS, DS, and HA differentially regulate the matrix microarchitecture of hydrogels due to their alterations to the kinetics of collagen self-assembly. In addition to providing information on how GAGs define key physical properties of the ECM, this work shows new ways in which stiffness measurements, microfluidics, microscopy, and turbidity kinetics can be used complementarily to reveal details of collagen self-assembly and structure. Statement of SignificanceCollagen and glycosaminoglycans (GAGs) are integral to the structure, function, and bioactivity of the extracellular matrix (ECM). Despite widespread interest in collagen-GAG composite hydrogels, there is a lack of quantitative understanding of how different GAGs alter the biophysical properties of the ECM across tissue, cellular, and subcellular length scales. Here we show using mechanical, microfluidic, microscopy, and analytical methods and measurements that the GAG molecules chondroitin sulfate, dermatan sulfate, and hyaluronic acid differentially regulate the mechanical, transport, and microstructural properties of hydrogels due to their alterations to the kinetics of collagen self-assembly. As such, these results will inform improved design and utilization of collagen-based scaffolds of tailored composition, mechanical properties, molecular availability due to mass transport, and microarchitecture.

Advances in the pharmacotherapeutic applications of hyaluronic acid: A comprehensive review

Natural non-sulfated glycosaminoglycan hyaluronic acid (HA), a biopolymer, has a variety of functions in controlling different biological processes. However, articular cartilage and synovial fluid contain more HA than other tissues and fluids. Over the past few decades, HA has been employed as a pharmacotherapeutic for a variety of conditions, such as osteoarthritis, cartilage regeneration, and wound healing. HA is used to create scaffold materials appropriate for tissue engineering because of its unique physicochemical characteristics. Recent cutting-edge research has shown that the molecular weight (Mw) of HA affects its efficacy. This paper provided a summary of recent developments in several pharmacotherapeutic applications and recommended research areas in order to improve HA activity.

Advances of Sulfonated Hyaluronic Acid in Biomaterials and Coatings—A Review

Hyaluronic acid (HA) is a non-sulfated glycosaminoglycan (GAG) that is a versatile material whose biological, chemical, and physical characteristics can be deeply tuned to modifications. However, HA is easy to decompose by hyaluronidase in vivo, and this process will reduce its structure and function stability during application. The sulfonation of HA can improve its stability under the action of hyaluronidase. Sulfated hyaluronic acid (S-HA) can be synthesized by many methods, and it shows significantly slower degradation by hyaluronidase compared with HA. In addition, negatively charged S-HA has other advantages such as anti-adhesive activity, anti-inflammatory, macromolecules by electrostatic interactions, stable site absorption of positively charged molecules, and enhancement of growth factor binding ability. It has numerous applications in medical (anti-aging, inflammation, tissue regeneration, cancer therapy, wound healing, and drug delivery) and cosmetics as biomaterials and coatings. In this article, the advances of S-HA for potential application of biomaterials and biomedical coatings will be reviewed and comprehensively discussed.

Evaluation of Non-Cross Linked Xeno-Free Hyaluronic Acid Solutions as Visco Elastic Biomaterials.

Hyaluronic acid (HA) is a naturally occurring biodegradable, high molecular weight, non-sulfated glycosaminoglycan (GAG) polymer known for its excellent biocompatibility. HA-based products are widely used as viscosupplements, dermal fillers, and ophthalmic lubricants in clinical settings. Although animal and bacterial-derived HA are commonly reported, plant-sourced HA is not frequently reported. In this study, we have evaluated various viscoelastic properties of one such plant-based HA solution and propose them as an alternative to existing animal/bacteria-sourced HA. The viscoelastic properties of plant-sourced HA solution of various concentrations (0.1%, 0.5%, 1%, and 2% in PBS) were studied using a rheometer at 37°C. Flow curves, amplitude sweep studies, and frequency sweep studies were performed and compared for all HA solutions. The HA solutions displayed shear-thinning behavior, which is an important characteristic of an injectable biomaterial. The 0.1 and 0.5% HA were found to have viscoelastic properties appropriate for eye lubricants, while 1 and 2% HA solutions showed properties suitable for soft tissue fillers. Frequency sweep studies indicated that all the samples are typically viscoelastic liquids with a loss modulus (G″) higher than the storage modulus (G'). This indicated that the samples needed further processing like crosslinking of HA or using higher molecular weight HA to be suitable as viscosupplements. However, the frequency sweep studies also indicated that these solutions can be used as soft tissue fillers of any type based on the G' and tan δ values. The plant-sourced HA solutions are found to exhibit good shear-thinning properties with viscoelastic properties suitable for eye lubricants and soft tissue fillers. However, to be used as viscosupplements, the viscoelastic properties of HA solutions have to be further modified through non-toxic crosslinking strategies, and hydrophobic derivatives as well as by using high molecular weight HAs.

Downstream process intensification for biotechnologically generated hyaluronic acid: Purification and characterization

Hyaluronic acid (HA), an anionic, non-sulfated glycosaminoglycan, has several clinical applications. This study examines several downstream methods for purifying HA with maximum recovery and purity. Following the fermentation of Streptococcus zooepidemicus MTCC 3523 to produce HA, the broth was thoroughly purified to separate cell debris and insoluble impurities using a filtration procedure and a variety of adsorbents for soluble impurities. Nucleic acids, proteins with high molecular weight, were successfully removed from the broth using activated carbons and XAD-7 resins. In contrast, insoluble and low molecular weight impurities were removed using diafiltration, with HA recovery of 79.16% and purity close to 90%. Different analytical and characterization procedures such as Fourier transform-infrared spectroscopy, X-ray diffraction, nuclear magnetic resonance, and scanning electron microscopy validated the presence, purity, and structure of HA. Microbial HA showed activity in tests for 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) radical-scavenging (4.87 ± 0.45kmolTE/g), total antioxidant capacity (13.32 ± 0.52%), hydroxyl radical-scavenging (32.03 ± 0.12%), and reducing power (24.85 ± 0.45%). The outcomes showed that the precipitation, adsorption, and diafiltration processes are suitable for extracting HA from a fermented broth under the chosen operating conditions. The HA produced was of pharmaceutical grade for non-injectable applications.

Hyaluronan and Reactive Oxygen Species Signaling-Novel Cues from the Matrix?

Hyaluronan (HA) is a naturally occurring non-sulfated glycosaminoglycan (GAG) localized to the cell surface and the tissue extracellular matrix (ECM). It is composed of disaccharides containing glucuronic acid and N-acetylglucosamine, is synthesized by the HA synthase (HAS) enzymes and is degraded by hyaluronidase (HYAL) or reactive oxygen and nitrogen species (ROS/RNS) actions. HA is deposited as a high molecular weight (HMW) polymer and degraded to low molecular weight (LMW) fragments and oligosaccharides. HA affects biological functions by interacting with HA-binding proteins (hyaladherins). HMW HA is anti-inflammatory, immunosuppressive, and antiangiogenic, whereas LMW HA has pro-inflammatory, pro-angiogenetic, and oncogenic effects. ROS/RNS naturally degrade HMW HA, albeit at enhanced levels during tissue injury and inflammatory processes. Thus, the degradation of endothelial glycocalyx HA by increased ROS challenges vascular integrity and can initiate several disease progressions. Conversely, HA exerts a vital role in wound healing through ROS-mediated HA modifications, which affect the innate immune system. The normal turnover of HA protects against matrix rigidification. Insufficient turnover leads to increased tissue rigidity, leading to tissue dysfunction. Both endogenous and exogenous HMW HA have a scavenging capacity against ROS. The interactions of ROS/RNS with HA are more complex than presently perceived and present an important research topic.

Microbial Hyaluronic Acid Production: A Review

Microbial production of hyaluronic acid (HA) is an area of research that has been gaining attention in recent years due to the increasing demand for this biopolymer for several industrial applications. Hyaluronic acid is a linear, non-sulfated glycosaminoglycan that is widely distributed in nature and is mainly composed of repeating units of N-acetylglucosamine and glucuronic acid. It has a wide and unique range of properties such as viscoelasticity, lubrication, and hydration, which makes it an attractive material for several industrial applications such as cosmetics, pharmaceuticals, and medical devices. This review presents and discusses the available fermentation strategies to produce hyaluronic acid.

Chitosan and hyaluronic-based hydrogels could promote the infected wound healing

The most important function of skin is to prevent biological dehydration and protect internal structures from the environment. When a wound becomes infected, the bacteria cause a sustained inflammatory response at the infected site, further delaying the healing process. Therefore, the search for better antibacterial strategies has become a topic of great concern. Therefore, the development of multifunctional hydrogels with antibacterial properties, ROS removal, and hemostasis is urgently required for promoting wound healing process. Chitosan is the only cationic natural polysaccharide with good biocompatibility, antibacterial and hemostatic ability. It is a candidate material to prepare hydrogel wound dressing. Hyaluronic acid (HA) is a natural biological macromolecule that belongs to a group of heteropolysaccharides known as non-sulfated glycosaminoglycans. It is a major component of the skin extracellular matrix (ECM) and is involved in inflammation, angiogenesis, and tissue regeneration. Here, the hydrogel was designed with the natural macromolecular of the gallic acid-grafted quaternized chitosan (GA-QCS) and oxidized hyaluronic acid (OHA) via Schiff base and/or Michael addition reaction. It was found that the GA-QCS/OHA hydrogel exhibited multifunctional capabilities with injectable, hemostasis, degradation, and release of medicines. In addiation, GA-QCS/OHA hydrogels exhibited remarkable antioxidant and migration promoting effects in vitro. And the mupirocin-loaded GA-QCS/OHA hydrogels had inhibitory effects on E. coli (Gram-negative bacterium) and S. aureus (Gram-positive bacterium) in vitro. A full-thickness skin of S. aureus infection mouse wound model was used to test the bioactive effect of the hydrogels and the accelerated wound healing was obtained due to the inhibiting the proinflammatory factor TNF-α and upregulating the vascularization factor CD31. This study proposed an effective strategy based on antioxidant, antibacterial, self-healing multifunctional hydrogel for wound healing under various infectious complications. This natural macromolecular hydrogel could act as an effective reactive oxygen species scavenger to promote the wound healing in the future.

Proteoglycans: A Tool for Detecting Hyaluronan by ELISA-Like Methods.

Hyaluronan is a non-sulfated glycosaminoglycan synthesized on the plasma membrane of almost all mammalian cells, which can interact with different proteoglycans of the extracellular matrix. Aggrecan, versican, neurocan, and brevican are proteoglycans whose structures present a specific protein domain called "link module," which allows hyaluronan binding. Therefore, they can be helpful for assays that detect hyaluronan. For example, ELISA-like methods developed to measure hyaluronan amounts in solution are based on specific interactions between this molecule and the link module present in aggrecan or other hyaluronan-binding proteins (hyaladherins).

Enzymatic Production of Low-Molecular-Weight Hyaluronan and Its Oligosaccharides: A Review and Prospects.

Hyaluronic acid (HA) is a nonsulfated linear glycosaminoglycan with a negative charge. Different from the high-molecular-weight HAs, the low-molecular-weight HAs (LMW-HAs, 4-120 kDa) and hyaluronan oligosaccharides (O-HAs, <4 kDa) exhibit certain unique biological properties, owing to which these have a wide range of applications in the field of medicine. However, the chemical synthesis of high-purity LMW-HAs and O-HAs requires complex procedures, which renders this process difficult to achieve. The degradation of HA is achieved under the catalysis of hyaluronidases. In recent years, various hyaluronidase genes have been identified, and their enzymatic properties have been analyzed. In this context, the present review summarizes the hyaluronidases from different sources, which have been characterized. The review focuses on the crystal structure and the catalytic mechanism underlying the biological properties of hyaluronidases. In addition, the molecular weight distributions and the preparation approaches of the enzymatic products LMW-HAs and O-HAs are described. The general orientation of the research on hyaluronidases was speculated based on the existing literature. Accordingly, the efficient large-scale production of LMW-HAs and O-HAs using the green enzymatic approach was anticipated.

Editorial of Special Issue “Hyaluronic Acid in Human Medicine”

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 [...].

Heparanase 2 (Hpa2) attenuates the growth of human sarcoma

The pro-tumorigenic properties of heparanase are well documented and established. In contrast, the role of heparanase 2 (Hpa2), a close homolog of heparanase, in cancer is not entirely clear. In carcinomas, Hpa2 is thought to attenuate tumor growth, possibly by inhibiting heparanase enzymatic activity. Here, we examine the role of Hpa2 in sarcoma, a group of rare tumors of mesenchymal origin, accounting for approximately 1% of all malignant tumors. Consistently, we found that overexpression of Hpa2 attenuates tumor growth while Hpa2 gene silencing results in bigger tumors. Mechanistically, attenuation of tumor growth by Hpa2 was associated with increased tumor stress conditions, involving ER stress, hypoxia, and JNK phosphorylation, leading to increased apoptotic cell death. In addition, overexpression of Hpa2 induces the expression of the p53 family member, p63 which, in sarcoma, functions to attenuate tumor growth. Moreover, we show that Hpa2 profoundly reduces stem cell characteristics of the sarcoma cells (stemness), most evident by failure of Hpa2 cells to grow as spheroids typical of cancer stem cells. Likewise, expression of CD44, a well-established cancer stem cell marker, was prominently decreased in Hpa2 cells. CD44 is also a cell surface receptor for hyaluronic acid (HA), a nonsulfated glycosaminoglycan that is enriched in connective tissues. Reduced expression of CD44 by Hpa2 may thus represent impaired cross-talk between Hpa2 and the extracellular matrix. Clinically, we found that Hpa2 is expressed by leiomyosarcoma tumor biopsies. Interestingly, nuclear localization of Hpa2 was associated with low-stage tumors. This finding opens a new direction in Hpa2 research.

HA-ADT suppresses esophageal squamous cell carcinoma progression via apoptosis promotion and autophagy inhibition

Esophageal squamous cell carcinoma (ESCC) is a major cause of cancer-related deaths. We have previously connected a non-sulfated glycosaminoglycan, hyaluronic acid (HA), with a common hydrogen sulfide (H2S) donor, 5-(4-hydroxyphenyl)-3H-1,2-dithiol-3-thione (ADT-OH), to reconstruct a novel conjugate, HA-ADT. In this study, we determined the effect of HA-ADT on the growth of ESCC. Our data suggested that HA-ADT exerted more potent effects than sodium hydrosulfide (NaHS, a fast H2S-releasing donor) and morpholin-4-ium (4-methoxyphenyl)-morpholin-4-ylsulfanylidenesulfido-λ5-phosphane (GYY4137, a slow H2S-releasing donor) on inhibiting the viability, proliferation, migration, and invasion of human ESCC cells. HA-ADT increased apoptosis by suppressing the protein expressions of phospho (p)-Ser473-protein kinase B (PKB/AKT), p-Tyr199/Tyr458-phosphatidylinositol 3-kinase (PI3K), and p-Ser2448-mammalian target of rapamycin (mTOR), but suppressed autophagy through the inhibition of the protein levels of p-Ser552-β‐catenin, p‐Ser9-glycogen synthase kinase‐3β (GSK-3β), and Wnt3a in human ESCC cells. In addition, HA-ADT was more effective in terms of the growth inhibition of human ESCC xenograft tumor than NaHS and GYY4137. In conclusion, HA-ADT can suppress ESCC progression via apoptosis promotion and autophagy inhibition. HA-ADT might be efficacious for the treatment of cancer.

Phytochemical screening and in vitro radical scavenging activities of “Gola” guava fruit and leaf extracts

This study aimed to investigate the chemical and antioxidant characteristics of 50% and 70% hydroethanolic Gola guava fruit (GF) and guava leaf (GL) extracts by high-performance liquid chromatography (HPLC) and Fourier-transform infrared spectroscopy (FTIR). Total phenolic content (TPC) was determined by Folin–Ciocalteu reagent. The ability to scavenge free radicals was evaluated using DPPH (2,2-diphenyl-1-picrylhydrazyl), H2O2 (hydrogen peroxide), and ABTS+ (2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)) in vitro assay. Fours hydroethanolic Gola GF and GL extracts (GF50%, GF70%, GL50%, and GL70%): 50% hydroethanolic leaves extract showed the highest TPC (299.06 ± 2.69 mg GAE/g dry extract) and TFC (31.05 ± 1.67 mg CE/g). GL50% (299.06 ± 2.69 mg GAE/g dry extract) showed high TPC than GL70%. While GL50% and GL70%’s antioxidant potential was higher than GF extracts. TPC showed a highly positive correlation with DPPH, H2O2, and a moderately positive correlation with ABTS·+. HPLC analysis indicated the presence of flavonoid compounds including quercetin and kaempferol as well as phenolic acids like gallic, syringic, m-coumaric, p-coumaric, vanillic, ferulic, benzoic, caffeic, chlorogenic, cinnamic, sinapic, and ascorbic acids. A high number of phenolic compounds was identified in GL50% followed by GF50% through HPLC. The extraction of bioactive compounds was more efficient with 50% hydroethanolic solvent. The FTIR spectrograms showed changes in the chemical groups and determined the extracts' functional groups. In conclusion, findings support the use of phenolic compounds extracted from GF and GL, not only for their antioxidant activity, but also provide an important basis for potential use of phenolic compounds as crosslinking agents of sulfated and non-sulfated glycosaminoglycan. Novelty impact statement This study manifests the best extraction solvent for optimized recovery of all antioxidant compounds of Gola GF and GL at maximum potential and provides an insight into the chemical profile of extracts. The chemical characterization by HPLC and FTIR pave the way for the possible natural antioxidant's formulation and development of functional food with a specific investigation to elucidate the action of mechanism at the cellular and organism level to evaluate the pharmacological potential of extracts.

Advances in Hyaluronic Acid for Biomedical Applications.

Hyaluronic acid (HA) is a large non-sulfated glycosaminoglycan that is the main component of the extracellular matrix (ECM). Because of its strong and diversified functions applied in broad fields, HA has been widely studied and reported previously. The molecular properties of HA and its derivatives, including a wide range of molecular weights but distinct effects on cells, moisture retention and anti-aging, and CD44 targeting, promised its role as a popular participant in tissue engineering, wound healing, cancer treatment, ophthalmology, and cosmetics. In recent years, HA and its derivatives have played an increasingly important role in the aforementioned biomedical fields in the formulation of coatings, nanoparticles, and hydrogels. This article highlights recent efforts in converting HA to smart formulation, such as multifunctional coatings, targeted nanoparticles, or injectable hydrogels, which are used in advanced biomedical application.