The Difference Between Hyaluronic Acid Powder and Hyaluronic Acid Hydrogel

Hyaluronic acid powder and the hydrogel derived from it are different physical forms of the same substance. You can think of their relationship simply as flour versus dough.

Hyaluronic acid powder is a dry, purified starting material obtained through extraction and purification. It consists essentially of linear polymer chains that dissolve easily in water to form a viscous solution. This solution offers excellent lubrication and moisture retention. However, this structure is temporary and reversible, with low mechanical strength. Moreover, it is rapidly broken down and cleared from the body. Therefore, the powder or solution form is primarily used in moisturizing serums, eye lubricants, or simple injectable fillers (which require pre-crosslinking).

In contrast, the hyaluronic acid hydrogel is a network structure in three dimensions achieved by the physical or chemical cross-linking of dispersed HA molecular chains. This network can trap a large amount of water to form a stable, elastic semi-solid. Unlike in powder form, the cross-linking enhances the HA to a much higher level in mechanical strength, resistance to enzymatic breakdown, and time present within the body. Because hydrogels can mimic the natural ECM more effectively, they are very useful where their sustained support and release are required.

In summary, powders and solution-based systems offer basic hydration functionality, with hydrogels that offer a sustained structural and functionality platform.

2. Methods for Preparing Hyaluronic Acid Hydrogel

Common methods for preparing HA hydrogels include physical crosslinking and chemical crosslinking. Physical crosslinking involves using physical crosslinkers (such as glutaraldehyde or carbodiimides) to react with HA molecular chains and form a network. Chemical crosslinking uses chemical crosslinkers to achieve the same. Here, we will use the chemical crosslinking method as an example.

The core of hydrogel preparation lies in introducing crosslinks. Following is a standard laboratory procedure that utilizes 1,4-butanediol diglycidyl ether (BDDE) cross-linking. It is important to point out that this procedure must be performed in a fume hood.

a. Dissolving Hyaluronic Acid

First, weigh the hyaluronic acid powder carefully and slowly add the powder to a container. The container should hold sterile distilled water or a buffer solution. Use strong mechanical stirring while adding the powder, which prevents the powder from forming lumps. This mixing process can take several hours. The final solution should be uniform and clear, with no bubbles and viscous. The concentration is usually between 1% and 3% weight per volume (w/v).

b. Adjusting pH

Make sure the HA is fully dissolved and keep stirring the solution. Slowly add a dilute sodium hydroxide (NaOH) solution. Monitor the pH while adding. Adjust the pH to between 7.0 and 7.4. The correct pH is very important because it makes the next crosslinking reaction efficient and stable.

c. Adding the Crosslinker

Continue stirring the pH-adjusted solution, and then slowly add a calculated amount of BDDE crosslinker. The amount is typically 0.5% to 2.0% of the dry weight of HA, but the exact amount depends on how crosslinked you want the gel to be. Mix well so the crosslinker spreads evenly. The BDDE contains epoxy groups. These groups react in a ring-opening reaction with hydroxyl groups on the HA chains. It forms strong covalent crosslinks between the HA molecules.

d. Gelation Reaction

Place the well-mixed solution into a constant-temperature water bath or oven. Heat it to between 70°C and 80°C. Use gentle stirring, like with a magnetic stirrer. Keep the heat and stirring for 1 to 2 hours to provide energy for the crosslinking reaction and the three-dimensional network. As the reaction happens, the solution will get much thicker and eventually form a smooth, uniform hydrogel.

e. Cooling and Sterilization

When the reaction is done, take out the gel, and let it cool down naturally to room temperature. Next, the gel needs to be purified and sterilized to remove any leftover crosslinker and by-products. This can be done by soaking or dialysis in water or saline. Sterilization makes the gel safe to use. A common method is autoclaving that uses steam at 121°C for about 15 minutes. Before using autoclaving, check that it does not harm the gel’s structure or properties.

By following these steps, you will get a chemically crosslinked hyaluronic acid hydrogel. The hydrogel can be used in different ways, and it can be cut into shapes and also be freeze-dried. Sometimes, drugs or cells are loaded into it.

In the End

Every step in the preparation process affects the final hydrogel. The molecular weight and concentration of HA matter. The pH and the type and amount of crosslinker also matter. Reaction temperature and time are critical, too. These factors control the hydrogel’s mechanical properties, affect how much it swells, determine how fast it degrades, and influence its biocompatibility. Therefore, you must systematically optimize these parameters based on how you plan to use the hydrogel.

For more information on hyaluronic acid, check out Stanford Chemicals Company.

Related articles:

10 Types of Functional Materials Made from Hyaluronic Acid

How is Hyaluronic Acid Powder Made

The post How to Prepare Hyaluronic Acid Hydrogel appeared first on Stanford Chemicals.

Importance of Molecular Weight

The molecular weight range of HA is extremely broad, ranging from several thousand to over two million Daltons. Products with different molecular weights possess distinct physicochemical properties and biological functions:

• High molecular weight hyaluronic acid exhibits strong hydration capacity and can form a highly viscous hydration network. High MW HA offers excellent lubrication, barrier protection, and spatial separation functions. It is mainly used in ophthalmic surgery as a viscoelastic agent, for arthritis injections, and as a film-forming moisturizer in high-end skincare products.
• Medium molecular weight hyaluronic acid combines certain viscoelasticity with tissue permeability. It is commonly used in dermal fillers to increase soft tissue volume and smooth out wrinkles.
• Low molecular weight and oligomeric hyaluronic acid have strong permeability and can be absorbed by the skin or cells. Studies show that specific low MW fragments can influence cell signaling and possess potential bioactivities such as anti-inflammatory, pro-angiogenic, or immunomodulatory effects. Hence, they are used in active skincare products and drug delivery systems.

How to Prepare High‑Molecular‑Weight Hyaluronic Acid

Industrially, high molecular weight HA is predominantly produced on a large scale via microbial fermentation, with the core focus on optimizing the biosynthesis process to maximize polymer chain length.

→ How is Hyaluronic Acid Powder Made

1. Strain Selection and Engineering

High-yield strains such as Streptococcus equi are typically used. Through genetic engineering techniques, the hyaluronic acid synthase gene is overexpressed, while genes encoding endogenous hyaluronidases are knocked out or suppressed, ensuring the synthesis of intact long chains and minimizing degradation from the source.

2. Precise Control of Fermentation Process

• Nutritional Control: Optimize the culture medium composition, particularly the feeding strategy of carbon sources (e.g., glucose), to ensure an adequate and balanced supply of synthesis precursors (UDP glucuronic acid and N acetylglucosamine).
• Environmental Parameter Control: Precisely maintain temperature, pH, and dissolved oxygen levels in the fermenter. Dissolved oxygen concentration is one of the key factors affecting molecular weight; it is usually maintained within an optimal range to support synthase activity while avoiding chain scission caused by oxidative stress.
• Shear Force Control: Fluid shear forces, due to mechanical agitation, may physically cause long chains to break. Thus, for minimum shear effect, optimization of agitation speed and fermenter design is essential to make sure of mixing and mass transfer efficiency.

3. Gentle Downstream Processing

Following fermentation, rapid inactivation, low temperature operations, and purification steps that avoid strong acid, strong base, or high shear forces are adopted, such as gentle membrane filtration or low temperature ethanol precipitation, to protect the integrity of the polymer chains.

How to Prepare Medium‑Molecular‑Weight Hyaluronic Acid

Two pathways generally exist to obtain the medium MW products: one is a direct fermentation control, and the other is controlled degradation of high MW starting material.

1. Fine‑Tuning via Fermentation Pathway

By manipulation of the above-mentioned fermentation parameters, chain extension can be deliberately restricted. For instance, a moderate rise in fermentation temperature, an altered dissolved oxygen strategy, or the addition of specific nutrient limitations at mid to late fermentation will direct the strain to produce hyaluronic acid within a pre-set molecular weight range. This approach indeed calls for profound knowledge regarding the metabolic network of the strain and process control.

2. Controlled Degradation of High‑MW Starting Material

This is the mainstream approach. Using high MW HA as the starting material, controlled degradation reactions are employed to break it down to the target range. Common methods include:

• Thermal Degradation: Heating an HA solution at a specific temperature (e.g., 80–95°C) for a defined period. The extent of molecular weight reduction is positively correlated with temperature and time. By real-time viscosity monitoring or sampling for molecular weight analysis, heating can be terminated when the target value is reached.
• Mild Chemical Degradation: Treatment with dilute acid or alkali solutions under heating conditions. Relatively controllable degradation can be achieved by strictly controlling the pH, concentration, temperature, and time of the reaction system.
• Physical Degradation: Such as ultrasonic degradation. The mechanical forces generated by ultrasonic cavitation are utilized to cleave glycosidic bonds. Degradation extent is controlled by adjusting ultrasonic power, duration, and solution concentration.

How to Prepare Low‑Molecular‑Weight Hyaluronic Acid

Producing low MW and oligomeric HA requires more intense or more specific chain-breaking methods.

1. Chemical Degradation Methods:

• Oxidative Degradation: Using hydrogen peroxide, ascorbic acid/metal ions (e.g., a redox system composed of vitamin C and copper sulfate), etc. This method is efficient. Adjusting oxidant concentration, temperature, and reaction time, low MW products ranging from several thousand to tens of thousands of Daltons can be obtained in a targeted manner.
• Acid/Alkaline Hydrolysis: Hydrolysis with relatively high concentrations of acid/alkali and higher temperatures. The process is more vigorous, and the molecular weight distribution of the resulting polymer may be quite broad. Careful regulation of the hydrolysis endpoint and prompt neutralization is hence necessary to fix the molecular weight of the polymer.

2. Enzymatic Digestion

This is the most accurate method. The method uses hyaluronidase for breakdown. The enzyme hydrolyzes the β1,4-glycosidic bond in HA molecules. The enzyme dose amount, concentration of the substrate, reaction temperature, and reaction time can accurately be controlled so that HA of low MW with narrow MW distribution can be synthesized with defined structures, even in terms of an oligosaccharide of defined degrees of polymerization. The reaction can be accurately terminated by heat inactivating the enzyme when the target molecular weight is achieved.

Risks and Challenges

Although technologies for controlling HA molecular weight are relatively mature, numerous challenges remain in actual production and application.

• Uniformity of Molecular Weight Distribution: Both fermentation and degradation processes yield a mixture of molecules with varying chain lengths. Achieving a narrow molecular weight distribution — a critical requirement for high-end applications such as pharmaceutical injections — demands advanced process monitoring coupled with refined separation and fractionation techniques, including ultrafiltration and chromatography.
• Structure–Activity Relationship: The bioactivity of low‑molecular‑weight HA does not correlate simply with a decrease in molecular weight. Specific molecular‑weight ranges — for instance, hexasaccharide fragments — can exhibit distinct receptor‑binding properties. The targeted production of such specific bioactive fractions remains an active area of research and a persistent challenge for industrial application.
• Precise Control of Degradation Processes: The kinetics of degradation reactions are complex and influenced by multiple variables. Implementing precise control over these processes at an industrial scale typically requires sophisticated analytical instrumentation, such as gel‑permeation chromatography coupled with multi‑angle laser light scattering detection.
• Final Product Safety and Stability: Residual chemical reagents or enzymes from the degradation process must be thoroughly removed to ensure compliance with pharmaceutical and cosmetic safety standards. Furthermore, low‑molecular‑weight HA solutions may demonstrate reduced stability, necessitating stricter controls in packaging and storage.

Summary

The preparation of hyaluronic acid with specific molecular weights is a comprehensive technology that involves microbial fermentation, polymer degradation, process control, and separation/purification.

Stanford Chemicals Company (SCC) has the capability to produce HA with a relatively narrow molecular weight range, which allows us to meet customers’ customized needs and has demonstrated good performance in practical applications.

The post How to Prepare Hyaluronic Acid with Controlled Molecular Weight appeared first on Stanford Chemicals.

Figure 1. Distribution of HA in the Human Body and Its Corresponding Concentrations

The image above shows the distribution of hyaluronic acid in the human body, with approximate concentrations as follows:

• Umbilical Cord: 4100 mg/L
• Synovial Fluid: 1400-3600 mg/L
• Vitreous Humor: 140-338 mg/L
• Skin: 200 mg/L
• Thoracic Lymph: 8.5-18 mg/L
• Ventricular Fluid: 0.053 mg/L
• Saliva: 0.46 mg/L
• Urine: 0.1-0.5 mg/L
• Aqueous Humor: 0.3-2.2 mg/L
• Lumbar Cerebrospinal Fluid: 0.02-0.32 mg/L
• Plasma: 0.03-0.18 mg/L

It is evident that HA concentrations are highest in the umbilical cord, joints, eyes, and skin. Because those areas require hyaluronic acid for its high viscoelasticity, moisture retention, or structural support. In contrast, concentrations are extremely low in areas like the circulatory system and cerebrospinal fluid. Amniotic fluid also contains a small amount of HA, which decreases sharply as pregnancy progresses.

Hyaluronic Acid in Joints

Hyaluronic acid is a major component of joint cartilage and synovial fluid. It plays a crucial role in maintaining normal joint movement.

• HA’s lubricating effect reduces friction between soft tissues and between cartilage surfaces.
• HA acts as a cushion, absorbing stress on joint cartilage.
• HA can inhibit the invasion of bacteria, toxins, and inflammatory mediators from outside the joint cavity, providing a good protective barrier function.
• HA can also help alleviate joint pain.

Without a doubt, hyaluronic acid is very important for joint health. Unfortunately, however, the amount of hyaluronic acid in the human body begins to decrease from the moment we are born. Furthermore, the body’s ability to synthesize hyaluronic acid gradually declines with age. If the relative HA content in the body at age 20 is set at 100%, it decreases to approximately 65% by age 30, 45% by age 50, and 25% by age 60. These are figures significant enough to warrant our attention.

Consequently, hyaluronic acid injections and oral supplements have become common methods for many people to alleviate joint problems. Sodium hyaluronate, the stable sodium salt form of HA, is a common clinical drug for treating osteoarthritis (OA). Patients with knee osteoarthritis can achieve temporary relief from joint pain through intra-articular injections of sodium hyaluronate medication. Oral intake of sodium hyaluronate can effectively relieve arthritis symptoms and protect joint function. Appropriate intake of HA can reduce the levels of bone resorption markers, pyridinoline and deoxypyridinoline, back to normal levels and increase bone density.

Reading more:

Hyaluronic Acid VS. Glucosamine VS. Chondroitin: Which Is Best for Joints?

Which is Better for Treating Arthritis: Injecting or Orally Taking Sodium Hyaluronate

Is Food-Grade HA Really Useful for Health?

Hyaluronic Acid in Skin

Hyaluronic acid is a naturally occurring moisturizing component in the skin. It is primarily distributed in the dermis, accounting for over 50% of the total HA content in the skin. The adult human body contains approximately 15g of HA, with about one-third of it being metabolized and renewed daily. However, its synthetic capacity gradually declines after the age of 25. By age 40, the HA content in the skin may be only 25% of what it was during infancy.

The most widely known skincare benefit of hyaluronic acid is its water-retaining and moisturizing ability. It is said that a single molecule of HA can hold up to 500 times its weight in water. In addition, thanks to its lubricity and viscoelasticity, it provides crucial structural support to the skin. Hyaluronic acid, together with collagen, helps maintain the elasticity and firmness of the dermis. Similarly, HA can also defend against external irritants and contribute to barrier repair.

Figure 2. Human skin structure: hyaluronic acid, collagen, fibroblasts, and elastin

Therefore, hyaluronic acid is frequently found in high-end skincare products. High Molecular Weight HA forms a protective film well on the skin’s surface, trapping moisture from the surroundings while shielding the skin from external irritants. Low Molecular Weight HA has better permeability. It can penetrate into the dermis, providing deep hydration while also stimulating skin cells to synthesize more natural HA, collagen, and elastin.

Reading more:

Hyaluronic Acid and Collagen: The Perfect Combination for Healthy Skin

Some HA ingredients that may appear in high-end skincare products:

• High Molecular Weight HA
• Low Molecular Weight HA (Oligo HA)
• Micro HA
• Sodium Acetylated Hyaluronate
• Cross-linked HA

Hyaluronic Acid in the Vitreous Humor

Hyaluronic acid was first isolated and identified from the vitreous humor of cow eyes. Well, in the human vitreous humor, hyaluronic acid is a key component for maintaining the normal structure and function of the eyeball.

The vitreous body mainly contains collagen fibrils and HA. And HA is fixed within the collagen network, giving the vitreous its solid gel state. This helps maintain intraocular pressure, preserve the spherical shape and transparency of the eyeball.

However, with age, the interaction between HA and collagen fibers gradually dissociates, leading to vitreous liquefaction and collagen fiber aggregation, which causes floaters. Furthermore, eye diseases such as retinopathy and macular conditions may be related to HA metabolism.

Consequently, sodium hyaluronate viscoelastic agents are widely used in ophthalmic surgeries (such as cataract, glaucoma, and corneal transplant procedures). This design principle is directly derived from the physical properties of HA in the vitreous—providing space maintenance, tissue protection, and lubrication. HA is also commonly used to treat dry eye syndrome. Some commercially available eye drop products that claim to treat dry eye are labeled as containing 0.1% sodium hyaluronate.

Hyaluronic Acid in Other Tissues

In embryonic development and the reproductive system, hyaluronic acid concentrations are extremely high in the umbilical cord, amniotic fluid, and placenta. Here, HA’s primary function is to construct a water-rich three-dimensional scaffold, providing a foundational environment for fetal cell growth, migration, and differentiation. It plays an important mechanical buffering and protective role.

Within the circulatory system, hyaluronic acid is a component of the extracellular matrix of blood vessel walls. It participates in regulating vascular permeability and compliance.

HA is also present in lymph fluid, assisting in tissue fluid balance and immune regulation.

On the surface of the oral mucosa, hyaluronic acid contributes to saliva lubrication and mucosal protection.

This widespread and precise distribution collectively illustrates the irreplaceable biological role of hyaluronic acid in maintaining the structural integrity of the human body, tissue homeostasis, and the process of life development.

FAQ: Hyaluronic Acid (HA)

1. What is hyaluronic acid, and where is it found in the body?

Hyaluronic acid is a naturally occurring compound found in the human body with high water-holding capacity, lubrication, viscoelasticity, biodegradability, and biocompatibility. It occurs throughout the body in many regions, like the vitreous bodies in the eye, joints, and umbilical

2. Does the amount of HA in the body change?

Yes. The levels of HA are highest at the time of birth, and then they start decreasing from there onwards. The body’s ability to produce HA decreases with age as well.

3. Why is HA important for joints?

HA is an important component of joint fluid and cartilage. It has lubricating effects and acts to prevent pain and inflammation of joints.

4. Can HA supplements help with joint problems?

Yes. Clinically, sodium hyaluronate (a stable form of HA) is used. Injections into the joint can provide temporary pain relief, and oral supplements may help ease symptoms and protect joint function.

5. What does HA do for the skin?

HA is an effective moisturizer that retains much water. This compound is responsible for providing support and skin elasticity through the collagen deposited on the skin surface that protects the skin barrier.

6. Are there different types of HA in skincare?

Yes. High Molecular Weight HA forms a protective layer on the skin’s surface. Low Molecular Weight HA can penetrate deeper to hydrate and stimulate the skin’s own HA and collagen production.

7. What role does HA play in the eyes?

The vitreous humor has a high concentration of hyaluronic acid, which helps to maintain the intraocular pressure, the shape, and the optical clarity of the eye. It is applied in eye surgery and dry eye treatments in the form of eye drops.

8. Where else in the body is HA important?

HA is crucial in the umbilical cord and amniotic fluid for fetal development. It’s also found in blood vessels, lymph, and saliva, where it aids in structure, balance, and lubrication.

The post Distribution of Hyaluronic Acid in the Human Body appeared first on Stanford Chemicals.

1. Injectable Hydrogels

Hyaluronic acid can form injectable hydrogels through physical or chemical crosslinking. These gels solidify inside the body under normal conditions or in response to stimuli like temperature or pH. Because they hold a lot of water and mimic natural tissue structure, they are often used in minimally invasive surgery, tissue repair, and slow-release drug delivery. For instance, HA hydrogels can be injected into joints to relieve osteoarthritis—they lubricate the joint and support cartilage healing.

Figure 1. Hyaluronic acid hydrogels

Cross-linked Hyaluronic Acid​ Gel HA Powder

2. Nano Drug Carriers

Hyaluronic acid can be turned into nanoparticles or micelles using methods like self-assembly or emulsification. These tiny carriers help deliver drugs precisely to targets. Since HA naturally binds to CD44 receptors—which are overexpressed on many cancer cells—it’s useful for delivering chemotherapy drugs, nucleic acids, or proteins directly to tumors. This targeted approach helps reduce side effects.

Figure 2. Formulations of hyaluronic acid (HA)-based nanomaterials.[1]

3. Electrospun Fiber Mats

By mixing hyaluronic acid with other polymers like collagen or polycaprolactone and electrospinning them, we can create nanofiber mats. These mats have a large surface area and a structure similar to natural fibers. They work well as wound dressings, vascular grafts, or nerve guides, helping cells attach, grow, and repair tissue.

Figure 3. Electrospun Fiber Membranes^[2]

4. 3D Printing Bioinks

Hyaluronic acid is often used in 3D bioprinting because of its flow properties and bioactivity. When modified—for example, with methacrylate groups—it can be cured with light to print detailed tissue scaffolds. These are used to engineer cartilage, skin, blood vessels, and more.

Figure 4. Hyaluronic acid for 3D bioprinting tissue engineering applications.[3]

5. Films & Coatings

Hyaluronic acid can be applied as a thin film or coating onto implants like artificial joints or heart stents. Techniques like spin-coating or grafting help create these layers. The coating improves compatibility with the body, reduces inflammation and scarring, and helps prevent bacterial growth.

6. Dissolving Microneedles

Hyaluronic acid can be made into small dissolving microneedles that carry active ingredients like vitamins, vaccines, or medicines. These microneedles painlessly pierce the top layer of skin and then dissolve, releasing what they carry. They’re used in skincare, vaccination, and managing chronic conditions.

Figure 5. Dissolvable hyaluronic acid microneedles (MNs)[4]

7. Tissue Glues & Sealants

Chemically modified HA—for example, with aldehyde or dopamine groups—can act as a strong biological adhesive, even on wet surfaces. It’s used in surgery to seal tissues, stop bleeding, or close leaks (like in spinal fluid), often replacing stitches and supporting faster healing.

8. Stimuli-Responsive Smart Materials

By tweaking its structure, hyaluronic acid can be designed to respond to specific body signals such as pH, enzymes, or redox changes. For example, an HA-based nanogel can break down quickly in the acidic, enzyme-rich tumor environment to release drugs right where they’re needed.

9. Composite Scaffolds

Combining HA with materials like hydroxyapatite, bioglass, or synthetic polymers produces strong, porous scaffolds. These are especially useful in bone repair—they provide mechanical support while encouraging bone cell growth and integration.

10. Eye Care Products

Hyaluronic acid is used in eye drops, gels, and corneal repair films because it retains moisture and lubricates well. It helps treat dry eyes, assists during cataract surgery, and aids in healing surface injuries. It can also extend how long a drug stays on the eye surface.

Summary

From the discussion of the ten materials above, it may be gleaned that research and current applications of HA have focused mainly on three aspects: (1) preparation of various derivatives and hydrogels using functional groups such as hydroxyls, carboxyls, and acetamido groups in HA molecules; (2) taking advantage of the interaction between HA molecules and receptors on the surface of cancer cells by using HA and its derivatives as drug carriers for targeted cancer treatment; and (3) developing further applications of HA hydrogels in fields like tissue engineering based on its close relationship with human physiological activities.

For more information on hyaluronic acid applications, check out Stanford Chemicals Company.

[1] Kim, J. H., Moon, M. J., Kim, D. Y., Heo, S. H., & Jeong, Y. Y. (2018). Hyaluronic Acid-Based Nanomaterials for Cancer Therapy. Polymers, 10(10), 1133. https://doi.org/10.3390/polym10101133

[2] Gruppuso, M., Iorio, F., Turco, G., Marsich, E., & Porrelli, D. (2022). Hyaluronic acid/lactose-modified chitosan electrospun wound dressings – Crosslinking and stability criticalities. Carbohydrate Polymers, 288, 119375. https://doi.org/10.1016/j.carbpol.2022.119375

[3] Ding, Y., Zhang, X., Mi, C., Qi, X., Zhou, J., & Wei, D. (2022). Recent advances in hyaluronic acid-based hydrogels for 3D bioprinting in tissue engineering applications. Smart Materials in Medicine, 4, 59-68. https://doi.org/10.1016/j.smaim.2022.07.003

[4] Fonseca, D. F., Vilela, C., Pinto, R. J., Bastos, V., Oliveira, H., Catarino, J., Faísca, P., Rosado, C., Silvestre, A. J., & Freire, C. S. (2020). Bacterial nanocellulose-hyaluronic acid microneedle patches for skin applications: In vitro and in vivo evaluation. Materials Science and Engineering: C, 118, 111350. https://doi.org/10.1016/j.msec.2020.111350

The post 10 Types of Functional Materials Made from Hyaluronic Acid appeared first on Stanford Chemicals.

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.

The post Does Low Molecular Weight Hyaluronic Acid Cause Inflammatory Reactions? appeared first on Stanford Chemicals.

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.

The post What Does Hyaluronic Acid Gel Do? appeared first on Stanford Chemicals.

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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