Hyaluronic acid is a naturally found chemical in the skin, joints, and other connective tissues of the body. It is a gel-like substance that plays a role in maintaining the hydration of the skin and tissues. It moisturizes skin, rejuvenates skin cells, and reduces the appearance of wrinkles and fine lines. 

Besides its application in cosmetics and skincare, there are many other important advantages of hyaluronic acid. It relieves joint pain and stiffness and helps in faster wound healing. In the form of eye drops, it is used to treat dry eyes.

It is a popular product in the cosmetic industry due to its unique ability to retain large amounts of water. Many of us want to know more about hyaluronic acid, its uses, and how we can reap its benefits. Hyaluronic acid creams are available that hydrate your skin and retain skin moisture. People can take hyaluronic acid as a supplement, or they can apply it topically as a cream. 

Hyaluronic acid is also used as an injectable dermal filler. The special properties of hyaluronic acid make it a suitable agent for dermal fillers. As part of the aging process, collagen, hyaluronic acid, and elasticity in the skin decrease causing wrinkles and saggy skin of the face. For removing wrinkles and plumping up the skin, dermal fillers are the solution. 

What is the difference between cross-linked and non-cross-linked Hyaluronic acid?

Differences between non-cross-linked and cross-linked hyaluronic acid

The molecular structure of hyaluronic acid is responsible for holding large amounts of water, thus helping to maintain skin hydration and firmness. In this article, we will discuss the two forms of hyaluronic acid and its benefits.

Depending on the composition of the acid, two types can be found: non-cross-linked hyaluronic acid and cross-linked hyaluronic acid. The naturally occurring hyaluronic acid in connective tissues of the body is linear or non-cross-linked. The physical properties, permeability, and degradation rate of cross-linked and non-cross-linked hyaluronic acid were studied in detail. In order to first understand the cross-linked and non-cross-linked hyaluronic acids, we need to understand their physical properties and clinical performance. 

Crosslinked hyaluronic acid-based gels have been widely used in the cosmetic industry as injectable dermal fillers. Cross-links are intermolecular bonds that enhance the stability and durability of clinical implants. 

Disintegration rate

Hyaluronic acid, in its natural form, is non-cross-linked and breaks down at a faster rate. Therefore it is chemically modified to create cross-linked HA which is a thicker gel. While cross-linked hyaluronic is far more stable and durable compared to its natural state. The process of cross-linking makes the product thicker and more difficult for the body’s enzymes to break down and disintegrate. 

This structure makes hyaluronic acid capable of retaining large amounts of water and providing hydration to the human body’s connective tissues for longer periods of time. The process of cross-linking makes the hyaluronic acid resistant to enzymatic breakdown and thereby it is able to remain in the body for months after filling. 

Longer-lasting effect

Cross-linked hyaluronic acid is longer-lasting and more stable compared to non-cross-linked or natural hyaluronic acid. So it is a better option for dermal fillers. When used for filling, its effect can last up to 12 months.  Because crosslinked hyaluronic acid is less susceptible to enzymatic degradation, it stays longer on the skin surface and so its anti-wrinkle effect is prolonged. 

What is the difference between cross-linked and non-cross-linked Hyaluronic acid?Diffusion and penetration

Some studies demonstrated that the formation of smaller particles of hyaluronic acid by means of cross-linking resulted in better diffusion and penetration through the human epidermis and animal skin as compared with linear or non-cross-linked hyaluronic acid. 






Elasticity and viscosity

From a physics point of view, elasticity is the property of an object which causes it to be restored to its original shape after distortion. Elastic and viscous properties of hyaluronic acid depend mainly on the concentration and cross-linking of hyaluronic acid. Cross-linked hyaluronic acid shows more elasticity and is more viscous than non-cross-linked or linear forms.

Skin penetration property

The size and molecular weight of a molecule inversely affect its skin penetration property. Hence a molecule with a higher molecular weight penetrates less deeply than one with a low molecular weight. Cross-linked hyaluronic acid has a greater size and higher molecular weight, hence it penetrates less. The cross-linked products stay in the site of filling for longer periods of time rather than getting diffused in deeper layers of skin. 

Adverse effects

The process of cross-linking involves the addition of certain chemicals to natural hyaluronic acid to increase its clinical performance and efficacy. However, this can lead to some potential adverse skin reactions. The common side effects associated with hyaluronic acid (HA) injection are local reactions such as swelling, pain, and itching. But in some cases, it may precipitate immunologic reactions and granulomas. It’s worth knowing, injection of hyaluronic acid into an artery or vein may result in embolization, with skin necrosis.

Blog about aesthetic medicine | Top Dermal


  1. Bingöl AÖ, Dogan A, Physical Properties of Hyaluronic Acid Fillers and their Relevance for Clinical Performance, Magazin für ästhetische Chirurgie, 2012, 2, 6-12. 
  2. Comparative Physical Properties of Hyaluronic Acid Dermal Fillers, Jeffrey Kablik 
  3. Cosmetic Injectables: Beyond the surface, Supplement to practical dermatology, June 2013 
  4. Weidmann MJ, New Hyaluronic acid filler for sub-dermal and long-lasting volume restoration of the face, European Dermatology, 2009, 1: 65-68. 
  5. Alsoufi A, New and innovative developments in hyaluronic acid fillers for lip enhancement and contouring, European Dermatology, 2010, 5: 50-53.
  6. Coleman S and the Plastic Surgery Educational Foundation DATA Committee, Cross-linked hyaluronic acid fillers, Plast Reconstr Surg, 2006, 117(2), 661-665. 
  7. Tezel A, Fredrickson GH, The science of hyaluronic acid dermal fillers, Journal of Cosmetic and Laser Therapy, 2008, 10: 35-42. 
  8. Duranti F, Salti G, Bovani B, Calandra M, Rosati ML, Injectable hyaluronic acid gel for soft tissue augmentation: A clinical and histological study; Dermatol Surg 1998