Hyaluronic acid is a natural linear polysaccharide occurring in the human body. Its molecular weight varies from several thousand to several million Daltons. High-molecular-weight hyaluronic acid (HMW-HA) has excellent moisture-retention and lubrication properties; thus, it can be widely used in cosmetics and medicine. However, recent research has revealed that low-molecular-weight hyaluronic acid (LMW-HA) and oligomeric hyaluronic acid (Oligo-HA), degradation products of HA, possess distinct biological activities compared with HMW-HA and thereby substantially expand the application range of HA.

1.1 Biological Activities of Low-Molecular-Weight and Oligomeric Hyaluronic Acid

The biological effects of LMW-HA and Oligo-HA depend on their molecular weight.

Fig 1. Comparison of Hyaluronic Acids with Different Molecular Weights

• Angiogenesis and Wound Healing: High-Molecular-Weight Hyaluronic Acid (HMW-HA) inhibits blood vessel formation. In contrast, Low-Molecular-Weight Hyaluronic Acid (LMW-HA), especially oligomeric fragments, promotes the proliferation and migration of endothelial cells. Therefore, LMW-HA accelerates angiogenesis. This process supports wound healing and tissue repair.
• Immune Regulation: HMW-HA has anti-inflammatory and immunosuppressive properties. However, LMW-HA acts as an agonist of Toll-like receptors, which activate dendritic cells and macrophages. This activation stimulates the release of pro-inflammatory cytokines and triggers immune responses. Because of this, LMW-HA is a promising candidate for antitumor immunity and vaccine adjuvants.
• Antioxidant Stress: Oligo-HA can scavenge free radicals to protect cells from oxidative damage. This property is generating growing interest in anti-aging and neuroprotection research.
• Promotion of Cell Proliferation and Migration: LMW-HA penetrates the skin barrier more effectively than HMW-HA. It encourages the proliferation of keratinocytes and fibroblasts, which helps in skin repair and regeneration.

1.2 Preparation for Low-Molecular-Weight and Oligomeric Hyaluronic Acid

Preparation of LMW-HA and Oligo-HA mainly relies on scission of intra-glycosidic bonds in the hyaluronic acid backbone. The three major approaches include physical, chemical, and enzymatic degradation. And each possesses different advantages and disadvantages regarding the mechanism of degradation, product molecular weight distribution, cost, and ecological impact.

2. Physical Degradation

Physical methods rely on external energy to disrupt chemical bonds in the HA polymer chain.

2.1 Thermal Degradation

This method relies on the principle of high temperature causing random cleavage of HA chains. The technique is quite simple and inexpensive, since no additional reagents are required. However, the process cannot be precisely controlled, and products obtained often have broad distributions of molecular weight. High temperatures may also lead to some changes in structure, affecting product purity and bioactivity.

2.2 Radiation Degradation

Gamma radiation or electron beams are used on HA solutions to create free radicals that cleave the glycosidic bonds. This method enables one to perform both degradation and sterilization in a very effective and concurrent manner. The main drawbacks of this method are high investment costs of equipment, safety risks, and complicated mechanisms of degradation that are very likely to be followed by side reactions, impairing the reproducibility of the structure of the final product.

2.3 Ultrasonic Degradation

Ultrasound causes cavitation in liquids, leading to the formation of microenvironments with very high temperature and pressure. These shear forces can effectively fragment HA chains. This approach is mild, fast, and environmentally friendly. What’s more, adjusting ultrasound power, duration, and solution concentration enables partial control over the molecular weight of the product. Given these advantages, ultrasonic degradation becomes a common choice for lab-scale and small-scale production.

3. Chemical Degradation

Chemical methods introduce reagents that trigger hydrolysis or redox reactions to break HA chains.

3.1 Acid or Alkaline Degradation

Under strong acid or alkaline conditions, such as HCl and NaOH, respectively, hydrolysis of the glycosidic bond proceeds in HA. Acidic hydrolysis primarily cleaves β-1,4 linkages of glucuronic acid, whereas alkaline hydrolysis predominantly breaks β-1,3 bonds of N-acetylglucosamine. Although this route is cheap and fast, it suffers from being harsh, and the process control is difficult, generally resulting in over-degradation products such as monosaccharides. The subsequent neutralization step and desalination further complicate the process and involve the generation of chemical waste.

3.2 Oxidative Degradation

Oxidation agents, including hydrogen peroxide and sodium periodate, can degrade HA effectively. The Vc/H₂O₂ redox system has attracted widespread interest because of its relatively mild and controllable reaction. The hydroxyl radicals produced in the process may attack the glycosidic bonds. Molecular weight could be reasonably well-controlled by adjusting the ratio, concentration, and reaction time of Vc and H₂O₂. However, it is possible that oxidation not only cleaves the glycosidic bonds but may also change the structure of hydroxyl groups on the HA chain, which may affect the chemical structure and bioactivity of the final product.

4. Enzymatic Degradation

Enzymatic degradation employs highly specific hyaluronidases to catalyze HA breakdown, representing the most promising approach for industrial production.

4.1 What are Hyaluronidases

Hyaluronidases are enzymes that specifically hydrolyze β-N-acetylhexosaminidic bonds in HA. Hyaluronidases are mainly classified by their origin. One type comes from microbes like Streptococci. They act as endoenzymes, which means they cut hyaluronic acid chains at random internal positions. As a result, they break down HA very effectively and are often used in industrial production.

Another type is derived from animals. A common example is testicular hyaluronidase. These animal-derived hyaluronidases are also endoenzymes. They are, however, widely used in scientific research and for making medicines.

Enzymatic degradation offers high specificity, requires milder reaction conditions, and produces fewer by-products. What’s more, by controlling the enzyme amount, reaction time, and temperature, products with narrow molecular weight distributions can be obtained.

4.2 Industrial Enzymatic Production for Low-Molecular-Weight and Oligomeric Hyaluronic Acid

Enzymatic degradation is the preferred method for industrial production of LMW-HA and Oligo-HA. A typical process involves several steps.

Fig 2. Enzymatic degradation [1]

1. First, the substrate is prepared. High-molecular-weight HA raw material is dissolved in a suitable buffer solution, forming a uniform mixture.
2. Next step, the enzymatic reaction takes place. A specific amount of microbial hyaluronidase is added to the HA solution. Stirring the mixture under controlled conditions. The temperature is maintained between 37–50°C, and the pH is kept at an optimal level.
3. During the reaction, the process is monitored. Viscosity changes are tracked in real time. Alternatively, molecular weight changes are followed. This is done using a viscometer or high-performance liquid chromatography.
4. The reaction is stopped when the target molecular weight is reached. Termination is achieved by raising the temperature. For example, heating above 80°C denatures the enzyme. Alternatively, changing the pH can also stop the reaction.
5. Finally, purification and drying are performed. The enzymatic hydrolysate is filtered. It is decolorized using activated carbon. Alcohol precipitation is then carried out. Centrifugation separates the product. The final powder is obtained through spray drying or freeze-drying.

This process can be precisely controlled. Suitable enzyme types are selected, reaction parameters are optimized, and immobilized enzyme technology may be used. Such controls enable reproducible results. Product molecular weight can be regulated from thousands to hundreds of thousands of Daltons to ensure the products meet various application requirements.

5. Conclusion

Low-molecular-weight hyaluronic acid and oligomeric hyaluronic acid have tremendous potential in pharmaceuticals, cosmetics, and functional foods, owing to their unique biological activities. The three major routes presently developed for their production include physical, chemical, and enzymatic degradations. Of these, enzymatic degradation of hyaluronic acid presents the best option for industrial precision production on a large scale because of its high efficiency, high specificity, mild conditions, and excellent controllability.

[1] Enzymatic Production of Low-Molecular-Weight Hyaluronan and Its Oligosaccharides: A Review and Prospects. Bo Pang, Hao Wang, Hao Huang, Lizhi Liao. Journal of Agricultural and Food Chemistry 2022 70 (44), 14129-14139. DOI: 10.1021/acs.jafc.2c05709

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1. What is Rheology?

Rheology is the science that studies the deformation and flow of matter. It bridges the gap between elasticity (like a spring, which can recover its shape) and fluid mechanics (like water, which flows). It answers the question: How will this material respond when I push, pull, or stir it?

2. What is Rheological Properties of Hyaluronic Acid?

Hyaluronic acid solutions are not simple, water-like liquids. They are typical non-Newtonian fluids, and their rheological properties are mainly reflected in the following aspects:

–High Shear-Thinning

This is the most well-known and crucial rheological property of hyaluronic acid.

Phenomenon: At rest or under low shear rates, it is very viscous, even gel-like. However, when subjected to high shear rates (e.g., rapid stirring, application massage, or injection through a fine needle), its viscosity drops dramatically, becoming as fluid as water.

Principle: At rest, the long-chain HA molecules entangle with each other, forming a vast, disordered network structure that creates high resistance to flow. Under high shear, these long chains temporarily align in the direction of flow, disentangling from each other, which significantly reduces flow resistance.

Application Examples:

• Aesthetic Injections:High-concentration Hyaluronic acid fillers are very viscous before injection. The shear-thinning property is key: it allows the viscosity to decrease as it’s pushed through the syringe and needle, making injection feasible. Once inside the tissue, the shear force disappears, and it instantly recovers its high viscosity, providing support and volume.
• Skincare Application:When you rub a serum between your palms, it feels thinner. But after applying it to the face, it recovers its viscosity, allowing it to adhere well to the skin.

–Viscoelasticity

Hyaluronic acid exhibits properties of both a viscous liquid and an elastic solid.

When you rapidly compress or stretch it, it can temporarily resist deformation and partially recover its shape after the force is removed. This property allows it to cushion impacts and protect tissues and cells. For example, in synovial fluid, the elasticity of HA helps cushion the impact between bones during jumping or running.

Conversely, under slow, continuous force, it flows like a liquid and dissipates energy. Thus, in joints, the viscosity of hyaluronic acid provides lubrication for smooth movement.

–Pseudoplasticity and Thixotropy

These properties are related to shear-thinning but have subtle differences.

• Pseudoplasticity: Refers to instantaneous shear-thinning and recovery. It thins immediately when force is applied and thickens immediately when the force is removed.
• Thixotropy: Refers to the viscosity taking some time to recover to its initial value after the shear force is removed. This is like ketchup: you shake it (applying shear) to thin it, and after pouring, it doesn’t thicken back instantly but takes a few seconds to recover.

Why Are Rheological Properties So Important?

These properties directly determine the function and application efficacy of hyaluronic acid in various fields:

In Aesthetic Medicine and Healthcare:

Rheological properties determine a filler’s lifting capacity, molding capability, injection smoothness, and persistence in the body. A well-designed HA filler must have precisely controlled rheological performance. Furthermore, appropriate viscoelasticity can help reduce injection pain and post-procedural swelling. When used as a viscoelastic agent in ophthalmic surgery or injected into joint cavities for arthritis treatment, its rheological properties provide protection and lubrication.

In Skincare:

The shear-thinning property provides a smooth, easy-to-spread experience. Its high viscoelasticity forms a breathable, moisturizing film on the skin’s surface, locking in moisture and providing a tightening effect. Whether an Hyaluronic acid serum feels slippery and non-greasy or sticky and stringy depends entirely on the rheological properties determined by the molecular weight and concentration of the hyaluronic acid used.

In Biological Functions:

In the extracellular matrix and synovial fluid, the rheological properties of hyaluronic acid are crucial for maintaining tissue structural integrity, regulating cell migration, and transmitting mechanical signals.

Summary

The rheological properties of hyaluronic acid are the scientific code describing “how it flows and deforms under force.” It is not a single parameter but a collection of behaviors (like shear-thinning, viscoelasticity). Understanding these properties not only explains why HA has certain sensory characteristics and efficacy in skincare and aesthetic products but is also the core scientific basis for designing and optimizing related products. Stanford Chemicals Company offers sodium hyaluronate powders with varying molecular weights and viscoelastic properties.

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Sodium hyaluronate and potassium hyaluronate—what’s the difference between these two similar ingredients?

Sodium Hyaluronate and Potassium Hyaluronate: Derivatives of Hyaluronic Acid

First, A key concept is that both sodium hyaluronate and potassium hyaluronate are derivatives of hyaluronic acid.

Hyaluronic acid itself is a large polysaccharide molecule. It has an unstable structure and is difficult to use directly. Turning it into a salt form greatly improves its stability and broadens its applications. So, whether it’s the “sodium” or “potassium” form, the core substance that provides moisturizing and reparative benefits to the skin is still hyaluronic acid. The fundamental difference lies in the cation—sodium ion (Na⁺) or potassium ion (K⁺).

Sodium Hyaluronate and Potassium Hyaluronate: the Difference in Molecular Weight

From a molecular weight perspective, there is no inherent difference between the two. Commercially available sodium and potassium hyaluronate products both cover a full range from low to high molecular weights. Differences in molecular weight do not come from the type of counterion but from the degree of polymerization controlled during manufacturing. Therefore, when discussing molecular weight, the key is to refer to the specific product’s specifications—not to assume one salt type naturally has a higher or lower molecular weight.

That said, the counterion does slightly affect hydration capacity, solution viscosity, and ionic strength. For example, at the same concentration and molecular weight, sodium ions have a smaller ionic radius and higher charge density. This allows them to attract water molecules more strongly, forming a thicker and more stable hydration layer. In comparison, potassium ions have lower charge density, resulting in a thinner and looser hydration layer. However, this difference is usually not decisive in practical applications.

	Sodium Hyaluronate	Potassium Hyaluronate
Core Structure	Long-chain hyaluronic acid polysaccharide
Structure
Molecular Formula	C₂₈H₄₄N₂NaO₂₃⁺	C₂₈H₄₄KN₂O₂₃⁺
Bound ions	Na⁺	K⁺

Sodium Hyaluronate and Potassium Hyaluronate: the Difference in Applications

1. Joint Injections and Medical Aesthetics

In this field, high molecular weight sodium hyaluronate is the dominant choice—especially for joint injections and dermal fillers. Its long-chain molecules form a highly viscoelastic 3D network in tissues. This provides excellent mechanical support and lubrication.

In orthopedics, this viscous supplementation therapy effectively relieves joint pain and improves function. In aesthetic medicine, sodium hyaluronate gels are cross-linked to enhance stability and longevity. They are widely used for wrinkle filling, facial contouring, and soft tissue volume restoration.

Potassium hyaluronate, on the other hand, is used differently in medicine. Its applications are often linked to the physiological role of potassium ions. A typical use is in certain ophthalmic surgeries, like cataract surgery, where it serves as a component of viscoelastic protective agents. Potassium ions are a key component of aqueous humor and are more compatible with ocular tissues. Potassium hyaluronate is also used in some oral supplements.

2. Skincare

In skincare, molecular weight determines penetration and function. Whether it’s the sodium or potassium form, both follow the same rules regarding molecular weight:

• High molecular weight: Cannot penetrate the skin. It forms a breathable hydrating film on the surface, locks in moisture effectively, and acts as a physical barrier.
• Low molecular weight: Can penetrate into deeper skin layers for intensive hydration.

Potassium hyaluronate is quite common in skincare, especially in formulas that focus on soothing and balancing the skin’s microenvironment. Potassium ions act as co-factors in the biosynthesis of skin ceramides. So, in theory, they can indirectly support skin barrier health.

3. Food and Health Supplements

Oral hyaluronic acid is taken to improve skin hydration and relieve joint discomfort. Studies suggest that low molecular weight hyaluronic acid (including both sodium and potassium salts) may be better absorbed in the intestines. In this area, sodium hyaluronate is the most studied and widely used form, with substantial clinical trial evidence in humans. Potassium hyaluronate is also used in some dietary supplements.

Summary

Both sodium hyaluronate and potassium hyaluronate are derivatives of hyaluronic acid. Their core difference lies not in the polysaccharide structure or molecular weight range, but in the counterion they carry—and the subtle physicochemical and biological effects that result. Sodium hyaluronate holds a dominant position due to its well-established use in medicine and extensive supporting research. Potassium hyaluronate, however, offers unique value in specific cases—such as ophthalmic surgery (where potassium ions play a physiological role) and certain skincare products focused on barrier repair.

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Low Molecular Weight Hyaluronic Acid Penetrates Deep into the Epidermis

In skincare, low molecular weight hyaluronic acid has long been considered more effective due to its excellent transdermal absorption, allowing it to penetrate deep into the basal layer of the epidermis. Researchers used Raman imaging to study the penetration of HA of different molecular weights into human skin tissue.[1] They found that among HA with molecular weights of 1000–1400 kDa, 100–300 kDa, and 20–50 kDa:

• 20–50 kDa HA can penetrate deep into the epidermis;
• 100–300 kDa HA can reach the stratum lucidum;
• Large molecular weight HA (1000–1400 kDa) remains only in the stratum corneum (at a depth of 25 μm).

Even smaller oligomeric hyaluronic acid can penetrate further into the dermis. This gives low molecular weight HA greater potential in moisturizing, repairing, and anti-aging.

Fig 1. High molecular weight vs. low molecular weight hyaluronic acid

Does Low Molecular Weight Hyaluronic Acid Cause Skin Inflammation?

It is widely known that hyaluronic acid is naturally present in the human body. In fact, the process of wound repair in the body involves the degradation and regeneration of HA:

1. High molecular weight HA aggregates to clear necrotic tissue and bacteria.
2. During the inflammation stage, high molecular weight HA degrades into low molecular weight HA, inducing cytokine production.
3. Angiogenesis and cell migration occur.
4. Fibroblast proliferation completes the repair process.

Fig 2. Involvement of hyaluronic acid in the wound-healing process[2]

In this process, low molecular weight hyaluronic acid does mediate certain inflammatory responses, such as immune cell aggregation and cytokine expression. However, this is a normal part of the repair mechanism and should not be simply viewed as a negative effect.

Multiple studies have shown that exogenous hyaluronic acid has beneficial effects on wound healing. Topical application of hyaluronic acid has been proven to accelerate skin wound healing in rats and hamsters. Other studies indicate that both high and low molecular weight Hyaluronic acid have anti-inflammatory effects in UVB-induced keratinocyte inflammation.[3]

Although some studies suggest that low molecular weight HA may cause increased inflammatory responses, the mechanism behind this phenomenon remains unclear. Some scholars argue that the inflammation observed in experiments may be due to contaminants in the samples. For example, FDA-related experiments showed that even HA with a molecular weight as low as 4.77 KDa did not cause inflammatory reactions in mouse macrophages.

The studies on the pro-inflammatory effects of LMW-HA have only been discussed in the context of injury, with no mention of its implications in daily skincare routines.

What Are the Functions of Low Molecular Weight Hyaluronic Acid?

In skincare, the greatest advantage of low molecular weight HA lies in its ability to be absorbed transdermally, providing deep moisturization. However, beyond moisturizing, low molecular weight HA has many other functions:

1. Promotes Cell Proliferation and Wound Healing

LMW-HA is widely present in the dermis, epidermis, and subcutaneous tissues of human skin, with the highest concentration in the dermis. It helps maintain skin structural stability by regulating moisture, osmotic pressure, and ion flow, and facilitates substance exchange. When tissue is injured, macrophages in the body gather at the wound site and secrete hyaluronidase. This enzyme breaks down endogenous high-molecular-weight hyaluronic acid into low-molecular-weight fragments. These small fragments act like an “alarm signal,” attracting immune cells and endothelial cells to migrate toward and accumulate at the injury site. During this process, endothelial cells proliferate and new blood vessels form, supplying oxygen and nutrients to the damaged tissue, thereby accelerating the repair process.

2. Anti-Photoaging

Skin aging is a complex process, and photoaging caused by ultraviolet (UV) radiation is a significant external factor. Studies show that under UVB exposure, the content of HA in the skin increases, with a notable rise in the proportion of low molecular weight HA. Thus, it can be said that LMW-HA participates in the skin’s anti-photoaging process and helps reduce photodamage.

Conclusion

There is currently insufficient evidence to suggest that low molecular weight HA used in skincare products causes harmful inflammation. On the contrary, it demonstrates significant efficacy in moisturizing, repairing, and anti-aging.

For other questions about HA, you can check our previous articles. If you are looking for sodium hyaluronate powder for use in cosmetics, eye drops, wound dressings, or medical devices, Stanford Chemical Company (SCC) is a good option.

• Is Hyaluronic Acid Antibacterial? Mechanisms and Applications
• How Hyaluronic Acid is Absorbed and Degraded in the Human Body
• What is Hyaluronic Acid Powder? Benefits and Usage
• Why Hyaluronic Acid is an Ideal Material for Wound Healing
• Hyaluronic Acid, Sodium Hyaluronate, Hydrolyzed Sodium Hyaluronate: What Are the Differences
• How is Hyaluronic Acid Powder Made

Reference:

[1] Essendoubi M, Gobinet C, Reynaud R, Angiboust JF, Manfait M, Piot O. Human skin penetration of hyaluronic acid of different molecular weights as probed by Raman spectroscopy. Skin Res Technol. 2016 Feb;22(1):55-62. doi: 10.1111/srt.12228. Epub 2015 Apr 16. PMID: 25877232.

[2] Bibire, Tudor & Yılmaz, Onur & Ghiciuc, Cristina & Bibire, Nela & Dănilă, Radu. (2022). Biopolymers for Surgical Applications. Coatings. 12. 211. 10.3390/coatings12020211.

[3] Liuying Hu, Satoshi Nomura, Yasunari Sato, Kyoko Takagi, Tsuyoshi Ishii, Yoichi Honma, Kenji Watanabe, Yoichi Mizukami, Jun Muto, Anti-inflammatory effects of differential molecular weight Hyaluronic acids on UVB-induced calprotectin-mediated keratinocyte inflammation, Journal of Dermatological Science, Volume 107, Issue 1, 2022, Pages 24-31, ISSN 0923-1811,https://doi.org/10.1016/j.jdermsci.2022.06.001.

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1. What is Hyaluronic Acid Gel?

Hyaluronic acid gel is a gel-like product, like figure 1. Its key ingredient is hyaluronic acid (HA), which naturally found in our skin, joints, and eyes. HA can hold up to 1000 times its weight in water.

Most hyaluronic acid gels available are not 100% pure HA. Instead, HA is the main active ingredient. It is mixed with water, thickeners (like carbomer), preservatives, and other beneficial ingredients. This creates a clear, lightweight gel that is easy to apply. It absorbs quickly and forms a breathable moisturizing layer on the skin.

Fig 1. HA gel

2. How is Hyaluronic Acid Gel Made?

Making hyaluronic acid gel involves biotechnology and precise formulation. The process has two main steps:

Step 1: Making the hyaluronic acid ingredient

Today, most HA is made through microbial fermentation:

• Bacteria like Streptococcus equi are grown in large tanks. They are fed nutrients such as glucose. These bacteria produce and release hyaluronic acid.
• The HA is then separated and purified. Impurities like proteins and nucleic acids are removed.
• The final product is dried and turned into a white powder—sodium hyaluronate. It can be processed into different molecular sizes:
  • High molecular weight: form a film on the skin to lock in moisture.
  • Medium molecular weight: provide moisture to the outer skin layers.
  • Low molecular weight: penetrate deeper into the skin for better hydration.

Step 2: Making the gel

Turning the powder into gel requires careful mixing:

• The powder is slowly added to purified water. It swells and forms a thick liquid.
• Thickeners like carbomer are added. The pH is adjusted to form a stable gel.
• Other ingredients are mixed in, such as moisturizers (e.g., glycerin), preservatives, and active compounds (e.g., vitamin B5 or centella extract).

Key factors for a good gel:

• Mixed molecular weights: better hydration at different skin levels.
• High purity: less likely to irritate, good for sensitive skin.
• Good formulation: affects stability, texture, and effectiveness.

* Stanford Chemicals Company (SCC) offers high-purity hyaluronic acid powder in various molecular weights. It is ideal for making hyaluronic acid gels.

3. Medical Uses of Hyaluronic Acid Gel

Hyaluronic acid gel is widely used in medical settings. For example, after orthopedic surgery, it can be applied to the treated area once nerves and tendons are repaired. It helps prevent tendon adhesions.

Additionally, after abdominal surgery, medical-grade hyaluronic acid can be sprinkled into the abdominal cavity following irrigation. It effectively protects the intestinal surgical site and prevents adhesions that could lead to bowel obstruction. It is also commonly used in gynecology to prevent adhesions.

Moreover, it can be used as an irrigation fluid during orthopedic surgeries. This helps reduce excessive inflammatory responses in the surgical area, minimizing scar formation. It may also serve other specific medical purposes.

4. Benefits of Hyaluronic Acid Gel for the Skin

Hyaluronic acid gel is a natural transparent polysaccharide. It was initially used mainly for moisturizing. Now, it is also used in wrinkle reduction and cosmetic procedures. It plumps the skin, smooths wrinkles, and enhances facial contours.

HA gel naturally exists in a gel-like form in the dermis of human skin. It helps store water and increases skin volume. However, its levels decrease with age. This causes the skin to lose moisture, leading to dullness, aging, and wrinkle formation.

Therefore, hyaluronic acid gel is primarily used in both medical and cosmetic fields.

5. Can Hyaluronic Acid Gel Remove Scars?

It does not significantly remove existing scars. Scars are a type of tissue that forms naturally as part of the skin’s healing process after injury. Applying hyaluronic acid gel has little effect on already formed scar tissue. Scars are a type of tissue that forms naturally as part of the skin’s healing process after injury. Applying hyaluronic acid gel has little effect on already formed scar tissue.

But if the gel is applied just after skin damage occurs, it can reduce inflammation and support skin repair. HA is a high-molecular-weight polysaccharide. It is widely distributed throughout the human body, especially in the skin. It is a normal component of the dermis and belongs to the connective tissue. Therefore, HA gel has anti-inflammatory effects and can be absorbed directly by the skin.

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Antibacterial Properties of Hyaluronic Acid

The antibacterial mechanism of hyaluronic acid is the result of both its physicochemical and biological properties. Unlike traditional antibiotics that directly kill bacteria, the unique molecular structure provides HA with a range of indirect yet essential antibacterial functions.

Fig 1. Structure and properties of hyaluronic acid and its application in antibacterial agents

• Anti-Adhesive Effect: This is the most direct and fundamental antibacterial mechanism. Hyaluronic acid molecules enable binding to a large amount of water, forming a highly hydrated, viscoelastic film on the skin or mucosal surface. This film effectively blocks pathogens from contacting epithelial cells, preventing initial bacterial colonization. Since bacterial biofilm formation begins with adhesion, HA stops infection at its source.
• Reduced Bacterial Tissue Permeability: Hyaluronic acid is a major component of the extracellular matrix. However, some pathogens, such as certain streptococci and staphylococci, secrete hyaluronidase, which breaks down HA in tissues. As a result, the extracellular matrix is ​​destroyed and infection is promoted. In response, exogenous HA supplementation can serve as a preventive measure. An excess of hyaluronic acid saturates the hyaluronidase produced by bacteria, preventing it from breaking down the extracellular matrix. This ultimately helps restrict bacterial penetration and spread.
• Immune Regulation and Synergy: High-molecular-weight HA has anti-inflammatory effects. It binds to CD44 receptors on immune cells, triggering cytoskeleton reorganization. This enhances the phagocytic ability of immune cells, helping to prevent excessive inflammation. On the other hand, low-molecular-weight HA acts as a signal released during inflammation, alerting the immune system to respond and clear pathogens.

Applications of Hyaluronic Acid in Antibacterial Formulations

While hyaluronic acid itself is not a potent bactericide, it serves as an excellent antibacterial enhancer and infection preventive agent.

1. Targeted Drug Delivery Systems

By virtue of HA’s specific binding ability to CD44 receptors, targeted drug delivery systems can be created for infection sites. Evidence shows that the combination of antibiotics like levofloxacin with HA maximizes drug concentration at the infection site significantly, promoting antibacterial activity and reducing systemic toxicity.

2. Smart Responsive Formulations

Based on the elevated hyaluronidase activity at infection sites due to bacteria, enzyme-sensitive drug delivery systems can be formulated. These formulations will remain stable in healthy tissue but will break down upon reaching infection sites due to bacterial hyaluronidase activity, delivering the drug specifically. This increases therapeutic response and reduces side effects.

3. Wound Dressings and Tissue Engineering

HA-based hydrogel dressings not only possess excellent water retention and gas permeability but also enable the sustained release of antibacterial medicines, creating a microenvironment for wound healing. New materials like silver nanoparticle-HA composite dressings have exhibited remarkable dual properties: antibacterial activity and promotion of tissue regeneration.

Reading more: Why Hyaluronic Acid is an Ideal Material for Wound Healing

4. Drug Delivery Carriers

Hyaluronic acid may improve the solubility and stability of many antibacterial drugs and improve their bioavailability by chemical modification or physical encapsulation. It acts as a carrier to reduce drug cytotoxicity and promote more effective therapy for intracellular infections.

Reference: Sodium Hyaluronate Coating for Drug Delivery

Challenges

Although HA shows great potential in antibacterial applications, several challenges remain:

• Endogenous hyaluronidase may prematurely break down exogenous HA.
• Different molecular weights of HA can lead to vastly different biological effects.
• The safety of large-scale clinical applications still requires further validation.

Future research should focus on:

• Developing novel hyaluronic acid derivatives resistant to enzymatic degradation.
• Optimizing the molecular weight distribution of HA-based formulations.
• Exploring synergistic effects between hyaluronic acid and other antibacterial agents.

As a natural biomaterial, HA’s unique antibacterial mechanisms offer broad application value. For more information on the properties and applications of hyaluronic acid, feel free to consult Stanford Chemicals Company (SCC). SCC offers various grades of safe, customizable sodium hyaluronate powder.

People Also Ask

Q: Is hyaluronic acid a disinfectant?

A: No, it’s not a disinfectant. It doesn’t directly kill germs but prevents infection by forming barriers and supporting the immune response.

Q: Does hyaluronic acid heal?

A: Yes, it heals wounds by suppressing inflammation, keeping the wound moist, and supporting tissue regeneration.

Q: Is hyaluronic acid safe? Can you put it on open wounds?

A: Yes, hyaluronic acid is safe and is used in wound care products to enhance faster wound healing and to create a moist environment.

Q: Is hyaluronic acid antibacterial?

A: Indirectly. It does not kill bacteria but inhibits bacterial adhesion and promotes natural defense mechanisms.

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Molecular Properties of Hyaluronic Acid

HA is a macromolecular polysaccharide. It is composed of D-glucuronic acid and N-acetyl-D-glucosamine repeating disaccharide units. Its molecular weight differs widely between a few thousand to a few million Daltons. This is the reason for its diverse functions.

Fig 1. Hyaluronic Acid Structure

In the periodontal environment, HA exhibits the following key properties:

• Excellent biocompatibility: It can be utilized safely in inflammatory tissue milieus.
• High viscoelasticity: It can be employed as a biological barrier and space-maintaining material.
• Hydrophilic and moisturizing: It keeps a wet state for wound healing.

Mechanism of Action of Hyaluronic Acid in Periodontal Treatment

The advantages of hyaluronic acid applied in periodontal therapy are predominantly because of its regenerative and anti-inflammatory properties. These properties are particularly helpful in patients with severe periodontal pathology. Inflammation is one of the principal reasons for the advancement of periodontal disease. Chronic inflammation continuously damages periodontal tissues. HA helps to reduce inflammatory responses and inhibit the destruction of periodontal tissues. At the same time, it may contribute to tissue repair, promote gingival healing, and facilitate periodontal regeneration.

Evidence-Based Basis for Clinical Application

As a biomaterial with certain antibacterial activity, hyaluronic acid exerts inhibitory activity against many periodontopathogens. Because of this, it is beneficial as an adjuvant therapy for gingivitis and periodontitis. Pirnazar et al.[1] demonstrated that 1300 kDa molecular weight hyaluronic acid in a concentration of 1 mg/ml significantly inhibits Propionibacterium acnes, Staphylococcus aureus, Prevotella oralis, and Aggregatibacter actinomycetemcomitans. Rodrigues et al.[2] also compared the antibacterial activity of an HA-containing mouthwash with chlorhexidine mouthwash. They observed that hyaluronic acid also suppresses Aggregatibacter actinomycetemcomitans and Prevotella intermedia but not Porphyromonas gingivalis.

Fig 2. HA antibacterial effects

In addition to antibacterial action, hyaluronic acid also promotes healing of periodontal tissue through multiple mechanisms, such as anti-inflammatory, anti-edema, pro-angiogenic, and osteoinduction processes. It is noteworthy that its biological functions are closely related to molecular weight. High molecular weight HA can inhibit the release of inflammatory factors, suppress immune responses, and promote wound healing. On the other hand, low and medium-molecular-weight HA can cause the expression of inflammatory factors at certain times. It helps in balancing inflammation and healing.

In non-surgical therapy, topical application of hyaluronic acid can contribute to subgingival debridement. It significantly enhances probing depth, clinical attachment level, and bleeding on probing. In surgical therapy, hyaluronic acid is applied as a regenerative adjunct. It enhances the repair of soft and hard tissues.

It is particularly noteworthy that hyaluronic acid has promising potential in correcting “black triangles” in the anterior region. A papilla deficiency of more than 2 mm can form a visual black triangle, which affects aesthetics. By giving intermittent, micro-volume injections (each <0.2 ml) 2–3 mm apical to the papilla tip, hyaluronic acid can restore the shape and vertical dimension of the gingival papilla. This effectively removes the black triangle and enhances smile aesthetics.

Frequently Asked Questions (FAQ) on the Application of Hyaluronic Acid in Periodontal Disease Treatment

Q: What is hyaluronic acid (HA)?

A: Hyaluronic acid is a naturally occurring glycosaminoglycan present everywhere in human tissues. It performs several biological functions such as moisturizing, repairing, and regulating inflammation.

Q: How does hyaluronic acid benefit the treatment of periodontal disease?

It assists in the healing of periodontal health by inhibiting periodontal pathogens, reducing inflammatory reactions, and promoting tissue regeneration and repair.

Q: Do hyaluronic acids of different molecular weights have different effects?

A: Yes. High molecular weight HA (>1000 kDa) is targeted against anti-inflammatory and barrier functions, and medium and low molecular weight HA can, in some circumstances, modulate inflammation and repair.

Q: Against which periodontal pathogens is hyaluronic acid effective?

A: Studies have demonstrated that it is capable of inhibiting bacteria such as Aggregatibacter actinomycetemcomitans and Prevotella intermedia, but is not very effective against Porphyromonas gingivalis.

Q: Can HA be used as a substitute for conventional periodontal therapies?

A: No. It is generally used as an adjunctive method, along with conventional treatments such as subgingival debridement and surgery for optimum effectiveness.

Q: How is hyaluronic acid applied in non-surgical treatment?

A: It is often given in gel form or by local injection into periodontal pockets to help decrease probing depth, bleeding, and promote attachment regeneration.

Q: Is it used for periodontal surgical treatment?

A: Yes. It is particularly useful in regenerative and mucogingival surgeries, augmenting the outcomes of soft and hard tissue repair.

Q: Can “black triangle” issues be treated with hyaluronic acid?

A: Yes. Through micro-injections in the gingival papilla, it can restore height and shape, and improve aesthetics in the anterior tooth area.

Q: Does the usage of hyaluronic acid have side effects or risks?

A: Due to its high biocompatibility, side effects are very rare. It may cause temporary local discomfort in a few patients, but it is generally safe.

Q: Are there hyaluronic acid products that patients can use?

A: Some HA-containing mouthwashes or gels are available for daily use by the patients, but for therapeutic purposes, they should be under dental supervision.

About The Hyaluronic Acid Powder Supplier: Stanford Chemical Company

Stanford Chemical Company (SCC) is a trusted supplier of sodium hyaluronate powder, offering a comprehensive range of high, medium, and low molecular weight pure hyaluronic acid powders. SCC’s HA products are safe and reliable, backed by the following certifications:

• ISO 9001 (Quality Management System)
• ISO 14001 (Environmental Management System)
• ISO 22000 (Food Safety Management System)

[1] Pirnazar P, Wolinsky L, Nachnani S, et al. Bacteriostatic effects of hyaluronic acid [J]. J Periodontol, 1999, 70 (4):370- 374

[2] Rodrigues S V, Acharya A B, Bhadbhade S, et al. Hyaluronan-containing mouthwash as an adjunctive plaque- control agent[J]. Oral Health Prev Dent, 2010, 8(4): 389- 394

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HA exists in various forms, including powder, liquid, and gel. Among, powder being the most stable and commonly used. If you’re considering to buy hyaluronic acid, you should understand its benefits, categories, and sources.

What Is Hyaluronic Acid?

This glycosaminoglycan acts as nature’s moisturizer. It is capable of holding up to 1,000 times its weight in water. Found abundantly in skin, joints, and eyes, it provides lubrication, hydration, and structural support. The natural hyaluronic acid in our bodies diminishes with age. It is why supplementation through skincare or oral products has become increasingly popular.

What Does Hyaluronic Acid Do?

1. Skin Hydration and Anti-Aging

Why is hyaluronic acid considered good for the skin? Because it enables hydration, holding 1000x its weight in water to plump fine lines and boost elasticity. It strengthens the skin barrier, soothes irritation, and works for all skin types without clogging pores. It’s the ability to retain moisture and support collagen.

2. Joint Lubrication

HA injections and oral supplements help lubricate joints, reducing pain and stiffness in osteoarthritis patients.

3. Wound Healing and Tissue Repair

Medical-grade HA accelerates tissue regeneration, making it useful in post-surgical recovery and chronic wound care.

4. Eye Health

Hyaluronic acid is a key ingredient in eye drops for dry eye syndrome, providing long-lasting lubrication.

Reading more: What is Sodium hyaluronate Powder? Benefits and Usage

Categories of Hyaluronic Acid by Application

Hyaluronic acid is segregated into different grades based on molecular weight and purity, each with a specific use.

1. Cosmetic-Grade Sodium hyaluronate

Used in skincare products like serums, creams, and masks, cosmetic-grade HA comes in various molecular weights:

• High Molecular Weight (HMW) HA: Forms a hydrating film on the skin’s surface, reducing trans-epidermal water loss.
• Low Molecular Weight (LMW) HA: Penetrates deeper into the skin for long-lasting hydration and collagen stimulation.

2. Medical-Grade Sodium hyaluronate

This grade is used in wound healing, eye drops (for dry eye treatment), and post-surgical recovery products. It has higher purity standards than cosmetic-grade HA.

Reference: Medical-Grade vs. Injectable-Grade Sodium Hyaluronate: Which Has Stricter Requirements

3. Injection-Grade Sodium hyaluronate

Injectable HA is highly purified and sterilized for use in:

• Dermal Fillers: To reduce wrinkles and add volume.
• Joint Injections: For osteoarthritis treatment (e.g., viscosupplementation).

This form requires stringent regulatory approval (e.g., FDA, CE) to ensure safety.

4. Food-Grade Sodium hyaluronate

In powder or capsule form, food-grade HA is applied to enhance joint well-being, skin moisturizing, and digestive health.

How is Hyaluronic Acid Produced?

Hyaluronic acid is naturally present in the human body, especially in the skin, joints and eyes, to lubricate and moisturize. Still, for commercial and industrial applications, have two main ways produced.

1. Animal Extraction

Previously, HA powder was obtained from animal tissue such as rooster combs and bovine vitreous humor. While it is functional, the method included a certain risk of allergic reaction and potential pollution. Furthermore, animal-derived HA is not vegan-compatible, leading to a shift towards microbial fermentation.

2. Bacterial Fermentation (Vegan Hyaluronic Acid)

Today, most commercial hyaluronic acid is produced by the streptococci or bacterial fermentation with other non-rational bacteria. This process causes high purity, reduces the incidence of animal-borne impurities, and is compliant with vegetarian and cruelty. Biofermented HA is now the product of choice for cosmetic, medical, and food-grade applications. Most good-quality HA sold today, including Stanford Chemicals Company, is produced by microbial fermentation.

Read more: How is Hyaluronic Acid Powder Made

Conclusion

Hyaluronic acid is a versatile compound ranging from skin care to medical treatment. Thanks to the progress of biofination, high-quality, vegetarian hyaluronic acid is now widely available. Whether you need sodium hyaluronate powder for supplements, injected for joint therapy, or cosmetic serum for glowing skin, understanding the different forms ensures the best option for your needs.

For premium-quality sodium hyaluronate powder tailored to various industries, please get in touch with Stanford Chemicals Company (SCC).

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Why is Sodium Hyaluronate Used in Drug Delivery

This is mainly attributed to its distinctive physicochemical and biological properties.

Sodium hyaluronate is a linear polysaccharide containing repeating disaccharide units, which contains lots of carboxyl groups (-COOH) and hydroxyl groups (-OH). Its structure renders it highly hydrophilic. It is water-soluble and can make very viscous solutions, which suits hydrophilic drug loading. Besides, its carboxyl groups and hydroxyl groups can be chemically modified to conjugate drug molecules or functional groups to construct intelligent delivery systems. The common modification methods involve esterification, amidation, and crosslinking.

Fig 1. The structures of sodium hyaluronate and its acetylated derivatives modified by esterification[1]

The structure of sodium hyaluronate provides the basis for drug delivery, while its biological properties are the key to the choice.

Hyaluronic acid is a natural ligand for CD44 receptor, which is highly expressed on most tumor cells, inflammatory tissues, and stem cells. HA-modified drug delivery systems are able to actively target these diseased tissues, enhancing local drug concentrations. CD44 is like a signal beacon, guiding HA to the locations of disease. Once the HA-coated drug reaches the target, it must be released in order to function. This is where the next key player enters: hyaluronidase. This enzyme degrades HA and, conveniently, is highly active in tumor or inflamed tissue. In the presence of hyaluronidase, the HA carrier degrades, releasing the therapeutic payload.

Hyaluronic Acid or Sodium Hyaluronate?

In the application of drug delivery systems, sodium hyaluronate is utilized instead of hyaluronic acid. Because the sodium salt form is more stable and more soluble in water at neutral or alkaline pH.

What Value Does Sodium Hyaluronate Coating Offer for Drug Delivery

1. Targeted Delivery

Shell drug carriers with HA enable selective binding to such receptors, enabling targeted delivery of the drugs to the disease cells or tissues. For example, HA-coated nanoparticles can deliver chemotherapy drugs specifically to tumor cells with less damage to healthy tissues and fewer side effects.

2. Enhanced Stability and Controlled Release

Sodium hyaluronate coatings protect encapsulated drugs from premature degradation and stabilize delivery systems. The viscoelastic formation of solutions by HA and the mucoadhesive properties enable sustained, controlled drug delivery with extended preservation of therapeutic levels at target sites. For instance, HA has been used to prepare sustained-release protein and peptide formulations, where traditional carriers like PLGA can cause inflammation and protein denaturation.

3. Versatility and Adaptability

Sodium hyaluronate coatings are biocompatible with multiple drug carriers, ranging from nanoparticles and liposomes to micelles. It is chemically tunable and may be conjugated with various therapeutic molecules such as small-molecule drugs, proteins, and nucleic acids. HA coatings may also be made responsive towards specific stimulants (e.g., pH or temperature stimuli), enabling controlled drug release at targeted locations.

4. Reduced Immunogenicity

As a naturally occurring substance in the human body, HA is biocompatible. It is less likely to trigger immune responses than synthetic materials. Sodium hyaluronate-coated nanoparticles are least familiar and recognized by the immune system, enhancing their shelf life and stability in the blood circulation for better target delivery.

Applications of Sodium Hyaluronate Coating in Drug Delivery

• Cancer treatment: Targeted drug delivery of chemotherapy drugs to cancer cells while minimizing systemic toxicity.
• Ocular drug delivery: Increasing the residence time and bioavailability of drugs in the eye for conditions such as glaucoma and dry eyes.
• Wound healing: Encouraging tissue repair and regeneration by delivering growth factors and other biomacromolecules to the injured area.
• Inflammatory arthritis treatment: Inflamed joint delivery of anti-inflammatory agents to alleviate inflammation and pain.
• Gene therapy: Enhancing the delivery efficiency and stability of gene vectors for targeted gene expression or silencing.
• Transdermal drug delivery: Enabling drug penetration through the skin for local and systemic delivery.

Conclusion

Sodium hyaluronate coatings are a powerful instrument in modern drug delivery that combines natural targeting functions with designed specificity. Employing HA’s inherent physicochemical properties and biological interactions, researchers can design systems to maximize therapeutic benefit while minimizing side effects. For more information, please check Stanford Chemicals Company (SCC).

[1] Chen, Fan & Guo, Xueping & Wu, Yue. (2023). Skin antiaging effects of a multiple mechanisms hyaluronan complex. Skin Research and Technology. 29. 10.1111/srt.13350.

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1. What Is Salicylic Acid?

Salicylic acid is a beta-hydroxy acid (BHA) derived from willow bark. It is oil-soluble, meaning it can penetrate deep into pores to dissolve excess sebum and dead skin cells.

Key Benefits of Salicylic Acid:

• Exfoliates the skin: Helps unclog pores and remove dead skin cells.
• Destroys acne: Deflates blackheads, whiteheads, and pimples by dissolving excess oil.
• Anti-inflammatory: Cools redness and inflammation of the acne.
• Enhances skin texture: Smooths out roughness and reduces the appearance of large pores.

Best For:

• Acne and oily skin
• Whiteheads and blackheads sufferers
• People with mild to moderate acne

Possible Side Effects:

• Can lead to dryness or irritation, particularly on sensitive skin
• Can make skin more sensitive to the sun, always use sunscreen.

The structure, origin, nature, and use of salicylic acid have been discussed in great detail in the preceding article, so we will not discuss them here. Interested readers can visit:

Salicin vs Salicylic Acid: Relationship, Difference & Uses

2. What Is Hyaluronic Acid?

Hyaluronic acid (HA) is a humectant, a water-absorbing molecule. It occurs naturally in the skin and provides hydration by holding up to 1,000 times its weight in water.

Major Advantages of Hyaluronic Acid:

• Deep hydration: Moisturizes and fills the skin, leaving it less dry.
• Improves skin elasticity: Makes the skin look youthful and soft.
• Soothes irritation: Gently calms sensitive or dry skin.
• All skin types may use light hydration, even oily skin.

Best For:

• dry, dehydrated skin
• Aging skin (keeps the skin from forming fine lines and wrinkles)
• sensitive or inflamed skin
• All skin types, even oily, as it is non-comedogenic.

Possible Side Effects:

• Seldom irritates, one of the gentlest skincare ingredients.
• Will take moisture out of the skin in extremely dry conditions if not sealed with a moisturizer.

For details on the properties, applications, benefits, and characteristics of hyaluronic acid, please refer to these articles:

Top 10 Benefits of Hyaluronic Acid

What is Hyaluronic Acid Powder? Benefits and Usage

Why Is Hyaluronic Acid Important?

High VS. Low Molecular Weight Hyaluronic Acid

3. Salicylic Acid vs. Hyaluronic Acid

Key Differences

Can You Use Them Together

The answer is yes. These two ingredients actually work very well in combination. Salicylic acid helps clean out your pores and stops breakouts from forming. In the meantime, hyaluronic acid restores moisture that might be stripped away while exfoliating. This creates a well-rounded skincare routine that treats acne without dehydrating the skin.

Which One Should You Choose

The best ingredient for you will be based on your skin type and concerns. For oily, spot-prone skin or pores that easily clog, salicylic acid is best. For skin that’s likely to be dry or dehydrated, hyaluronic acid is better suited. For most people, they find they need both – salicylic acid for spots and hyaluronic acid for staving off dryness. The combination approach enables you to reap the benefits of acne treatment while still having healthy, hydrated skin.

Final Verdict

Salicylic acid and hyaluronic acid serve totally different purposes but can beautifully complement one another. Salicylic acid is your go-to for breakout clearing, and hyaluronic acid helps to keep your skin hydrated and plump.

If you’re dealing with acne, incorporate salicylic acid carefully, and always follow up with hyaluronic acid to prevent dryness. For those with dry or aging skin, hyaluronic acid alone can provide a major hydration boost.

About Stanford Chemicals Company (SCC)

Stanford Chemicals Company (SCC) supports businesses and research communities with such critical compounds as sodium hyaluronate, salicin, salicylic acid, dihydromyricetin, and chondroitin sulfate.

If you need quality substances, we’d be delighted to help. Feel free to contact us for more details.

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