Introduction: Managing Knee Osteoarthritis with Hyaluronic Acid Injections

Knee osteoarthritis is a common and often painful condition affecting millions worldwide. As this wear-and-tear disease progresses, patients typically experience stiffness, swelling, and difficulty moving. While surgery can be an option, many seek less invasive treatments to ease their symptoms. Among these, injections of hyaluronic acid-based gels have become a popular choice. These gels aim to supplement the joint’s natural fluid, providing cushioning and lubrication to reduce pain and improve movement. In this article, we compare five widely used knee gel injection brands—Synvisc, Euflexxa, GELSYN-3, Hyalgan, and Gel-One—looking at how they are administered, how long the relief lasts, and what real-world performance reveals, helping you better understand what each offers.

Types of Knee Gel Injections and How They Work

Hyaluronic acid (HA) is a naturally occurring substance found in the fluid inside our joints, acting like a lubricant and shock absorber. Knee gel injections typically contain HA that helps replenish this fluid, easing pain and improving function. However, not all HA injections are the same. Some use cross-linked HA, which means the molecules are chemically bonded to increase their size and durability, allowing the gel to stay longer in the joint. Others use non-cross-linked HA, which may be absorbed more quickly. Furthermore, some products source HA from animal tissue, while others use synthetic or biofermentation processes, which can affect allergy risks and overall safety.

Introducing Arthrosamid: A New Polyacrylamide Hydrogel

A newcomer to the scene is Arthrosamid, a gel based on polyacrylamide (PAAG), recently introduced in the UK. Unlike traditional HA gels, Arthrosamid works by "adhering to and bulking up the synovial membrane," effectively providing a scaffold that supports the joint lining (synovium). This novel approach offers an alternative way to relieve pain and improve joint function in knee osteoarthritis.

Injection Protocols: How Often and How Much?

Different gel brands require varying numbers of injections and volumes, which can affect convenience and patient comfort. Synvisc typically involves three injections spaced one week apart, whereas Synvisc-One delivers its full dose in just one session of 6 mL. Euflexxa and GELSYN-3 also commonly follow a three-injection, one-per-week schedule with 2 mL per dose. Hyalgan requires the most injections, with five weekly doses of 2 mL each. Gel-One is more convenient with a single 3 mL injection, aided by its cross-linked composition that helps it last longer. The number and frequency of injections influence the overall treatment experience, so patients and doctors often weigh effectiveness against ease when making their choices.

How Long Does the Pain Relief Last?

The duration of relief from these injections varies and depends largely on their composition and dosing schedules. Synvisc and Euflexxa often provide relief lasting up to six months, sometimes even longer. GELSYN-3 and Hyalgan tend to offer pain reduction from three to six months. Gel-One, thanks to its single, cross-linked injection, generally provides similar relief length to Synvisc-One, about six months. Direct comparisons, for example between Synvisc and Euflexxa, find both effective in easing pain and improving joint mobility. Differences like those between GELSYN-3 and Hyalgan usually come down to injection frequency and HA concentration. Overall, while these gels are broadly helpful, individual responses may vary.

What About Arthrosamid?

When it comes to Arthrosamid, recent clinical studies suggest promising results. One report highlights that this PAAG hydrogel shows "efficacy at one year post injection," with some studies demonstrating benefits extending up to two years. In fact, a clinical trial found Arthrosamid’s pain relief effects "approached superiority" to those of Synvisc-One after 52 weeks. It even showed statistically significant better outcomes for younger patients, those with a normal body mass index (BMI), and individuals with moderate osteoarthritis (KL grade 2–3). These findings suggest Arthrosamid can be a valuable alternative, especially for these groups.

What Makes Each Brand Unique?

Each knee gel injection brand has particular features that might influence your choice:

• Synvisc contains animal-derived, cross-linked HA with a high molecular weight, which may help it stay in the joint longer.
• Euflexxa is made from non-animal, biofermentation-derived HA, which lowers the risk of allergic reactions and is non-cross-linked.
• GELSYN-3 uses moderately cross-linked HA aiming to balance duration and absorption.
• Hyalgan has a lower molecular weight and non-cross-linked, animal-derived HA, requiring more frequent dosing.
• Gel-One is a single-injection, cross-linked synthetic HA designed for prolonged effect and patient convenience.

For Arthrosamid, the polyacrylamide hydrogel is unique in its ability to "bulk up the synovial membrane" and has been shown to be safe with "no long-lasting adverse events reported." Though long-term superiority over HA is still under investigation, it offers an intriguing alternative for pain relief in knee osteoarthritis.

Choosing the Right Injection: What Patients and Doctors Consider

Selecting the best knee gel injection depends on various factors beyond pure effectiveness. Ease of use, such as preferring fewer injections, plays a big role for many patients. Cost and insurance coverage also influence decisions, as some brands may be more affordable or better reimbursed than others. Doctors will consider your history, such as any allergies to animal products, your overall health, and severity of arthritis. While some may favour the convenience of single injections like Synvisc-One or Gel-One, others might opt for multiple injections if evidence suggests better relief. Arthrosamid's demonstrated tolerance and intermediate-term benefits may make it appealing for patients considering alternatives to traditional HA injections.

What Do Patients Say?

Patient feedback generally aligns with the scientific findings. Synvisc and Euflexxa are often praised for pain relief and improved movement, although some people find multiple injections uncomfortable. Hyalgan's safety record is well regarded, but the longer injection schedule can be less convenient. GELSYN-3 balances injection frequency and effectiveness well, leading to good patient adherence. Gel-One scores high on convenience thanks to a single injection, but doctors sometimes call for more long-term data. Importantly, polyacrylamide hydrogel such as Arthrosamid has shown the highest patient satisfaction rates reported in certain studies — with up to 72% of patients happy with their symptoms at 3 months, maintaining decent satisfaction at 6 and 12 months.

Conclusion: Finding the Best Fit for Your Knee Osteoarthritis

In summary, Synvisc, Euflexxa, GELSYN-3, Hyalgan, and Gel-One are all effective hyaluronic acid-based injections providing significant relief for knee osteoarthritis. The best choice varies depending on your individual preferences, medical history, and how you value convenience versus treatment protocol. Emerging options like Arthrosamid, with its longer-lasting scaffold-like action and favourable safety profile, add to the treatment possibilities. Ultimately, discussing your options with your healthcare provider will help ensure an informed decision tailored to your needs. As research in this area continues, patients can look forward to ever more personalised and effective approaches to managing knee osteoarthritis.

References

Cole, A., Maulana, R. K., Whitehead, J. P., & Lee, P. Y. F. (2022). A systematic review of the novel compound Arthrosamid polyacrylamide (PAAG) hydrogel for treatment of knee osteoarthritis. Medical Research Archives, 10(8). https://doi.org/10.18103/mra.v10i8.2950
Bliddal, H., Beier, J., Hartkopp, A., Conaghan, P. G., & Henriksen, M. (2023). Polyacrylamide hydrogel versus hyaluronic acid in knee osteoarthritis: A subgroup analysis of a randomized study. Orthopaedic Proceedings, 105-B(SUPP_13), 81–81. https://doi.org/10.1302/1358-992x.2023.13.081
Aykaç, B., Dinç, M., Nar, Ö. O., Karasu, R., & Bayrak, H. Ç. (2025). Comparative efficacy of polyacrylamide hydrogel versus hyaluronic acid and corticosteroids in knee osteoarthritis: A retrospective cohort study. Medicine, 104(38), e44655. https://doi.org/10.1097/md.0000000000044655