What to Know About Gel-One (Cross-Linked Hyaluronate)

An Injectable Hyaluronate Gel for Osteoarthritis

Gel-One (cross-linked hyaluronate) is a treatment option for osteoarthritis (OA) of the knee. It is an injection that helps manage the associated pain.

It’s derived from a protein (hyaluronan) extracted from the combs, or crests, of chickens, which the human body naturally produces to lubricate joints. It works by restoring levels of this protein.

First approved by the Food and Drug Administration (FDA) in 2001, Gel-One was only evaluated in a single clinical trial and was shown to be effective for up to 13 weeks in reducing pain scores, but other endpoints, including stiffness and physical function, were not found to be statistically different than placebo.

There is no outright cure for OA. This treatment is typically only given after other means of management, such as taking medications or adjusting lifestyle, have been attempted.

As with any medication, Gel-One injections aren’t without their side effects and risks. If you have OA, it’s important to understand as much as you can about your treatment options.

Older person experiencing pain from knee osteoarthritis

Nattakorn Maneerat / iStock / Getty Images


Gel-One is indicated for OA of the knee, which is characterized by the wearing down of joints, leading to pain. OA is the most common form of arthritis, and while it can affect anyone, it’s most often seen in those over 65.

Primarily, Gel-One will be attempted when other treatments, such as taking nonsteroidal anti-inflammatory drugs (NSAIDs) or physical therapy, aren’t yielding results. Since OA is a progressive and irreversible condition, while surgery may be an option, treating it typically means managing symptoms. This injection represents a solid, additional therapy.

Before Taking

Proper diagnosis of OA is essential before Gel-One injections are considered as treatment. How is this condition assessed? Here’s a quick breakdown:

  • Assessment of symptoms: The first step in diagnosis involves evaluating medical history and discussing the extent of pain, inflammation, stiffness, “locking,” and other symptoms in the affected knee.
  • Imaging: While healthcare providers may often be able to diagnose OA based on the evaluation of symptoms, they may need to employ an X-ray to assess the scope of the condition. Magnetic resonance imaging (MRI) or computed tomography (CT) will be used in rarer cases.
  • Testing: While blood tests and the like aren’t usually necessary, they may be used if conditions like gout or rheumatoid arthritis are suspected.

Precautions and Contraindications

As with any medication, Gel-One isn’t recommended for certain classes of patients, including:

  • Repeat patients: The safety of multiple Gel-One injections or a Gel-One injection alongside another injected treatment in the same knee has not been established.
  • OA in other joints: This treatment is not recommended for those with arthritis in joints other than the knee.
  • Skin infection: This treatment is not recommended if the skin on the knee in question is damaged or there’s an infection that contraindicates use.
  • Other kinds of arthritis: Gel-One is only approved for use against OA.
  • Pregnancy and nursing: Researchers and healthcare providers aren’t sure if this medication is safe for people who are pregnant or nursing.
  • Under 21: It’s not known if it’s safe for children and patients below the age of 21.
  • Certain allergies: Let your practitioner know if you have a known allergy to cinnamon, avian proteins, eggs, or feathers, as these are risks for an allergy to this medication.

Talk to Your Healthcare Provider About What You're Taking

Talk to your healthcare provider about all medications, supplements, and vitamins that you currently take. While some drugs pose minor interaction risks, others may outright contraindicate use or prompt careful consideration of whether the pros of treatment outweigh the cons in your case.

Other Hyaluronic Acids

Derivatives of hyaluronic acids, sold under names including Restylane, Juvéderm, and Perlane, are facial fillers used to smooth wrinkles or perform lip augmentation. As in joints, hyaluronic acid levels decrease as you age, loosening the skin. By injecting these into the face, the skin fills in and becomes tighter.

Also, dentists may use a topical version of hyaluronic acid as part of the treatment regimen for chronic gum inflammation. Alongside other courses of treatment, it will help reduce this inflammation in these areas, helping treat gingivitis, periodontitis, and other issues.


Gel-One injections are only ever administered by healthcare providers in the hospital setting, and, as mentioned, more than one such treatment per knee isn’t recommended. It comes in a pre-filled glass syringe containing 3 milliliters (mL) of the solution, which has 30 milligrams (mg) of hyaluronic acid.

The Seigaku Corporation, which manufactures Gel-One, and the FDA emphasize that multiple doses or alterations to the prescription are not recommended. Still, if you’re unsure, be sure to talk to your practitioner about the right dosage for you.

How to Take and Store

Though administration and storage are up to your healthcare provider, it’s important to understand what this should look like. Proper Gel-One use looks like this:

  • Storage: Syringes of the solution should be kept in a cool environment below 71 F but above freezing. Any unused portions should be discarded, and the injection should be thrown out and not used if the packaging has been opened.
  • Administration: Before injection, your practitioner will ensure that the surface of the affected knee is thoroughly cleaned off to prevent infection.
  • Afterward: If you’ve been given a Gel-One shot, you’ll need to avoid strenuous activities (as in most sports, heavy exercises, etc.) for at least 48 hours.

Side Effects


The more common side effects of Gel-One injection tend to resolve; however, you should let your healthcare provider know if these persist or become problematic. They include:

  • Joint swelling
  • Fluid in the knee
  • Pain at the injection site
  • Affected walking
  • Hand or feet swelling
  • Headache, dizziness
  • Aches of the back, other joints, or muscles
  • Sore throat, runny nose, and sneezing

After treatment, be mindful of how you’re feeling. Don’t hesitate to seek help if you think you need it.


Severe reactions to Gel-One are rare, with most arising from allergic reactions to the medication. If you experience any of the following, get help immediately:

  • Swelling in the face, lips, tongue, throat, or mouth
  • Paleness
  • Low blood pressure
  • Breathing difficulties
  • Hives
  • Itchiness
  • Cold sweats
  • Heavy pain and swelling in the knee following treatment 

Warnings and Interactions

What makes Gel-One generally very tolerable is that this medication is administered by a healthcare provider, thus reducing the chance of overdose. Since it’s also typically not administered multiple times (at least in the same knee), the chances of a poor interaction between this drug and others you’re taking are very low.

Significantly, though, you should not undergo Gel-One injection if your skin has been cleaned with disinfections made with quaternary ammonium salts. There is a chance that the medication may react to this type of solution.

Frequently Asked Questions

  • Is a Gel-One injection safe?

    The Food and Drug Administration (FDA) considers the Gel-One injection to be reasonably safe. In a study conducted on different groups of participants, there were no serious adverse effects reported by either group. However, it is always a good idea to have a conversation with your healthcare provider about whether the Gel-One injection is right for you. In addition, the Gel-One injection hasn't been studied in people younger than 21 or pregnant women, so people belonging to these groups should have a conversation with their doctor first.

  • Is Gel-One effective?

    Gel-One is considered an effective long-term treatment for osteoarthritis. However, it may not be as effective in the short-term; an analysis on corticosteroid injections versus hyaluronic acid injections found that the corticosteroids were more effective in the short-term period, while hyaluronic injections had longer-lasting effectiveness but were more slow in their effectiveness.

6 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Food and Drug Administration (FDA). Package Insert: Gel-One (Cross-Linked Hyaluronate).

  2. Food and Drug Administration (FDA). Summary of Safety and Effectiveness Data: Hyaluronic Acid.

  3. Sinusis K. Osteoarthritis: Diagnosis and treatment. Am Fam Physician. 2012;85(1):49-56.

  4. Seigaku Corporation. Patient Information: Gel One.

  5. Casale M, Moffa A, Vella P, et al. Hyaluronic acid: Perspectives in dentistry. A systematic review. Int J Immunopathol Pharmacol. 2016;29(4):572-582.

  6. Sinusas K. Osteoarthritis: diagnosis and treatment. Erratum in: Am Fam Physician. 2012;86(10):893. PMID:22230308

By Mark Gurarie
Mark Gurarie is a freelance writer, editor, and adjunct lecturer of writing composition at George Washington University.