In general, HA is categorized into different grades based on the application. Besides the usual cosmetic grade, medical-grade, food-grade, and injectable-grade HA also have extensive market applications. We have already touched on the variations between these types of hyaluronic acid. If you’re curious, click on the following link to learn more: Medical Grade vs. Cosmetic Grade Hyaluronic Acid: What Are the Differences.

HA was first discovered to be added to medicine over 70 years ago. It has continued to be a constantly increasing part of life sciences and medicine through continued research.

Medical Grade Hyaluronic Acid Was First Used in Ophthalmology

Hyaluronic acid is a multi-purpose matrix that occurs widely in the human body. It possesses a good lubricant and biocompatibility. Medically, it is referred to as sodium hyaluronate and is utilized in various ophthalmic surgeries, such as intraocular lens implantation, corneal transplantation, and glaucoma surgery.

Actually, the therapeutic application of HA dates back 70 years. HA was first successfully used in eye surgeries in the 1950s and remains a common practice to this day. Two decades later, HA’s moisturizing property was beautifully utilized by veterinarians when they filled horse joints with HA to improve mobility. Since then, HA has steadily expanded its role in medicine.

Read more: From Surgery to Daily Care: The Versatile Role of Sodium Hyaluronate in Eye Health

The Diverse Benefits of Medical-Grade Hyaluronic Acid

Presently, with more and more research, applications of HA in medicine are growing day by day. Besides its traditional use in ophthalmology, HA has become a major treatment modality for orthopedic conditions. In osteoarthritis and frozen shoulder, joint lubrication is greatly improved by HA injections, and cartilage is protected.

Moreover, HA use now includes gynecology, tendon fixation, and abdominal surgery, wherein it is utilized as a postoperative device. Its bioadhesive nature allows it to form a protective coating over wounds, both as a lubricant and as a mechanical coating to give the optimal environment for healing.[i] Lastly, HA supplementation is now a standard therapy for cystitis and urinary tract infection, significantly alleviating signs and symptoms with its mucosal protective effect.

HA is also pushing vaccine technology forward. By some chemical manipulations, HA holds pioneering promise as an adjuvant. When mixed with antigens, it enhances antigen-presenting efficacy, induces targeted migration to lymph nodes, and prevents inflammation at the injection site[ii]—offering new conceptual paradigms for vaccine design.

The Role of Hyaluronic Acid Depends on Its Molecular Weight

Low-molecular-weight HA (LMW-HA) can penetrate tissues better, possesses fine bioactivity, and is, therefore, good for anti-inflammatory and tissue repair. Medium-molecular-weight HA (MMW-HA) offers a balance between lubrication and structure. High-molecular-weight HA (HMW-HA) excels in viscoelasticity and water retentive properties. Each of the molecular weight forms has something special to offer—no one “best” one, merely the best for a given purpose. Each has a specific molecular weight range suited to a specific medical application and functional requirement.

The next table provides a working comparison of HA’s properties demanded and molecular weight associated for various medical applications:

This structured comparison serves as a reference for clinical decision-making or product development, emphasizing that optimal HA selection depends on specific medical requirements.

[i] Belluco C, Meggiolaro F, Pressato D, Pavesio A, Bigon E, Donà M, Forlin M, Nitti D, Lise M. Prevention of postsurgical adhesions with an autocrosslinked hyaluronan derivative gel. J Surg Res. 2001 Oct;100(2):217-21. doi: 10.1006/jsre.2001.6248. PMID: 11592796.

[ii] Jiang D, Liang J, Noble PW. Hyaluronan as an immune regulator in human diseases. Physiol Rev. 2011 Jan;91(1):221-64. doi: 10.1152/physrev.00052.2009. PMID: 21248167; PMCID: PMC3051404.

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What is Hyaluronic Acid

Hyaluronic Acid (HA) is a polysaccharide naturally found in the connective tissues, skin, joint fluid, and eyes of the human body. It has a unique ability to retain water and is an important structural component in living organisms.

Benefits of Hyaluronic Acid

Due to its biocompatibility and versatility, HA is widely used in medicine, cosmetology, and bioengineering.

1. Joint Health

Hyaluronic acid plays a crucial role in joint health as a major component of synovial fluid, which lubricates and cushions the joints. It helps reduce friction between the joints, alleviating pain and improving mobility. This is particularly beneficial for individuals with osteoarthritis, as HA can help relieve symptoms and slow disease progression.

2. Ophthalmic Applications

In ophthalmology, hyaluronic acid is widely used in eye drops to relieve dry eye symptoms, providing long-lasting lubrication and comfort. During eye surgeries, HA is used to protect and repair corneal tissue, accelerate postoperative recovery, and reduce complications.

3. Tissue Repair and Regeneration

Hyaluronic acid promotes tissue repair and regeneration by stimulating cell proliferation and migration, speeding up the wound-healing process. It is beneficial in treating burns, ulcers, and other skin injuries, helping to reduce scar formation and enhance the quality of skin repair.

4. Anti-inflammatory and Immune Regulation

Hyaluronic acid exhibits significant anti-inflammatory and immune-regulating properties. It can reduce the release of inflammatory mediators, lowering inflammation and minimizing tissue damage. Additionally, HA can modulate the immune system, enhancing the body’s defense mechanisms and helping to alleviate chronic inflammatory conditions.

5. Beauty and Skincare

In the field of beauty and skincare, hyaluronic acid is highly prized for its exceptional moisturizing capabilities. It can deeply hydrate the skin, increasing its water content, making it soft, and smooth, and reducing the appearance of fine lines and wrinkles. HA also promotes collagen production, enhancing skin elasticity and firmness, thus improving overall skin quality.

What is Molecular Weight

Molecular weight (MW), also known as relative molecular mass, is the sum of the masses of all the atoms in a molecule. It is used to measure the size of a molecule and is typically expressed in Daltons (Da) or atomic mass units (AMU).

Calculating the MW of hyaluronic acid is complex because it is a high-molecular-weight polysaccharide made up of repeating disaccharide units (glucuronic acid and N-acetylglucosamine). The molecular weight depends on the chain length, i.e., the number of disaccharide units.

Fig 1. Hyaluronic acid chemical structure

In practice, the molecular weight of HA is usually expressed as a range. Low molecular weight HA is less than 200 kDa, medium molecular weight HA ranges from 200 to 1800 kDa, and high molecular weight HA is greater than 1800 kDa. These ranges represent the average number of disaccharide units in HA molecules, not precise single values.

How Molecular Weight Affects Hyaluronic Acid’s Efficacy

The molecular weight of HA significantly influences its biological activity and efficacy.

1. Differences in Viscoelasticity and Lubricity

High molecular weight HA (typically over 1800 kDa) is widely used to treat arthritis due to its excellent viscoelastic and lubricating properties. It enhances the viscosity of joint fluid, reducing friction, pain, and inflammation. This type of HA is usually injected directly into the joint cavity for maximum effect. On the other hand, Medium molecular weight HA (200-1800 kDa) is also used for joint health, often found in oral or injectable supplements. It provides lubrication and cushioning within the joint cavity, improving joint mobility and flexibility.

In ophthalmic surgery, high molecular weight HA is commonly used, such as in cataract surgery and corneal transplants. Its high viscosity and viscoelasticity protect eye tissues, reducing mechanical damage during surgery. Conversely, low molecular weight HA (usually less than 200 kDa) is often used in eye drops. It effectively keeps the eyes moist, alleviating dry eye symptoms and improving eye comfort.

Fig 2. Low molecular weight hyaluronic acid eye drops

2. Different Effects on Wound Healing

Tissue Repair and Regeneration: In tissue engineering and regenerative medicine, high molecular weight HA is often used as a critical component of biomaterials and tissue engineering. Its structure can mimic the natural extracellular matrix, providing support and signals for cells, promoting cell migration, and tissue regeneration. Low molecular weight HA, due to its smaller molecular size, can better penetrate tissues, promoting wound healing and skin repair by activating fibroblasts and keratinocytes, accelerating the tissue regeneration process.

Fig 3. In the process of wound healing, different molecular weight hyaluronic acid has different effects

3. Variations in Anti-inflammatory and Immunomodulatory Effects

Anti-inflammatory and Immune Regulation: The role of HA in anti-inflammatory and immune regulation is also influenced by its molecular weight. Medium molecular weight HA shows certain advantages in anti-inflammatory and immune regulation. It can bind to cell surface receptors, regulating immune responses, and reducing inflammation, and is used to treat inflammatory diseases such as ulcerative colitis and Crohn’s disease. Low molecular weight HA has shown potential in some studies to regulate the immune system and promote antigen presentation, and immune responses, making it promising in vaccine development.

4. Varied Moisturizing Effects

Beauty and Skincare: In beauty and skincare, high molecular weight HA is mainly used for surface hydration in skincare products, forming a protective layer, reducing water loss, and enhancing skin smoothness. In contrast, low molecular weight HA can penetrate deeper into the skin, promoting hydration in the dermis layer, enhancing skin elasticity, and reducing fine lines and wrinkles, providing deeper skincare effects.

Fig 4. Varied Moisturizing Effects of High VS. Low Hyaluronic Acid

Conclusion

In summary, the molecular weight of HA significantly impacts its efficacy in different fields. High molecular weight HA is mainly used in applications requiring viscoelasticity and lubrication, such as joint health and ophthalmic surgery. In contrast, low molecular weight HA, due to its good permeability and biological activity, is more suitable for tissue repair, anti-inflammatory, immune regulation, and deep skin care. Choosing the appropriate molecular weight of HA can maximize its efficacy and meet the needs of different applications.

Stanford Chemical Company (SCC) is a pioneer in the development of hyaluronic acid. In addition to providing customers with food-grade, medical-grade, cosmetic-grade, and injectable-grade hyaluronic acid, we can also provide users with sodium hyaluronate powder with different molecular weights. For more information or specific applications, please visit our homepage.

Related reading:

Comparative Analysis of Hyaluronic Acid with Different Molecular Weights

High VS. Low Molecular Weight Hyaluronic Acid

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