What Is Gelsyn-3?
Gelsyn-3 is a hyaluronic acid (HA) injection treatment for knee osteoarthritis. Administered as three weekly injections, it’s produced through bacterial fermentation rather than from animal sources—making it safe for patients with egg or poultry allergies.
Manufactured by Bioventus (the same company that makes Durolane), Gelsyn-3 provides an effective middle-ground option: the proven efficacy of a three-injection series with the safety profile of a non-avian product.
Quick Facts: Gelsyn-3 at a Glance
3 weekly injections (once per week for 3 weeks)
Bacterial fermentation (biofermented) - non-avian
4-6 months of pain relief in clinical studies
$500-$800 full course; $75-$200 with insurance
| Detail | Specification |
|---|---|
| FDA approval | Yes, for knee osteoarthritis |
| Molecular weight | Medium-high (1.0-2.9 million Daltons) |
| Volume per injection | 2 mL |
| Total treatment | 6 mL over 3 weeks |
| Egg allergy safe | Yes |
| Medicare coverage | Yes (when medically necessary) |
| Manufacturer | Bioventus |
Is Gelsyn-3 Right for You?
You May Be a Good Candidate If:
When Gelsyn-3 May Not Be Ideal
How Gelsyn-3 Works
The Science: Restoring Joint Cushioning
Healthy knee joints contain synovial fluid rich in hyaluronic acid—a natural lubricant and shock absorber. In osteoarthritis:
- HA breaks down and becomes less effective
- Cartilage loses cushioning as fluid quality declines
- Bones rub together causing pain and inflammation
- Movement becomes painful and range of motion decreases
Gelsyn-3 works by:
- Replenishing the joint’s natural HA
- Improving lubrication to reduce friction
- Cushioning the joint during weight-bearing activities
- Reducing inflammation and pain signals
Why Biofermented HA?
Unlike older HA products derived from chicken combs, Gelsyn-3 uses bacterial fermentation technology:
Advantages of Biofermented HA:
- No animal proteins - Eliminates allergy concerns
- Consistent molecular structure - More uniform product
- High purity - Fewer contaminants
- Sustainable production - Less environmental impact
- Similar to natural HA - Better biocompatibility
The Three-Visit Treatment Protocol
Week 1: First Injection
What happens:
- Initial consultation and joint assessment
- Knee area cleaned and prepared
- 2 mL Gelsyn-3 injected into knee joint
- Post-injection instructions provided
After first injection:
- Mild soreness for 1-2 days is normal
- Apply ice as needed
- Avoid strenuous activity for 48 hours
- You may not notice relief yet—that’s normal
Week 2: Second Injection
What happens:
- Brief check-in about first injection
- Second 2 mL injection administered
- Continue activity modification
What to expect:
- Some patients start noticing subtle improvements
- Injection site reactions typically milder than first visit
- Continue ice and rest protocol
Week 3: Third Injection
What happens:
- Final 2 mL injection completes treatment course
- Discussion of expected timeline for benefits
- Follow-up appointment scheduled
After completion:
- Full benefits typically develop over 4-8 weeks
- Gradual return to normal activities
- Relief can last 4-6 months or longer
Timeline of Relief
| Timeframe | What to Expect |
|---|---|
| Week 1 | Injection site soreness; no relief yet |
| Weeks 2-3 | Some patients notice early improvement |
| Weeks 4-8 | Progressive pain reduction and improved mobility |
| Months 2-6 | Peak benefit period with maximum relief |
| Beyond 6 months | Benefits may continue; repeat treatment if needed |
Effectiveness: What Research Shows
Clinical Evidence
Multiple studies support the effectiveness of three-injection HA protocols:
Meta-Analysis Findings:
A comprehensive review of hyaluronic acid injections found that three-injection regimens (like Gelsyn-3) demonstrated:
- Significant pain reduction compared to placebo
- Improved function scores on standardized assessments
- 4-6 month duration of meaningful benefit
- Favorable safety profile with low complication rates
Real-World Success Rates
Clinical experience with Gelsyn-3 and similar three-injection products shows:
- 50-70% of patients report meaningful pain relief
- Improved walking distance and stair climbing ability
- Reduced need for pain medications in many patients
- Delayed knee replacement in appropriate candidates
Factors That Improve Outcomes
You’re more likely to benefit if you have:
- Mild-moderate arthritis (Kellgren-Lawrence grades 2-3)
- Good joint alignment without severe deformity
- Reasonable body weight for your height
- Active lifestyle goals you want to maintain
- Realistic expectations about improvement (not cure)
Side Effects and Safety
Common Side Effects
Most side effects are mild and temporary:
| Side Effect | Frequency | What to Do |
|---|---|---|
| Injection site pain | Common | Ice, acetaminophen |
| Mild swelling | Common | Ice, elevation |
| Temporary stiffness | Occasional | Light movement |
| Bruising | Occasional | Apply ice |
| Warmth at site | Occasional | Normal; monitor |
Rare but Serious Reactions
Seek medical attention if you experience:
- Severe pain that worsens after 48 hours
- Significant swelling or joint warmth
- Fever or chills (may indicate infection)
- Inability to bear weight on treated knee
- Red streaking from injection site
These symptoms are rare but require prompt evaluation.
What Makes Gelsyn-3 Safe?
- Non-avian source eliminates poultry allergy risk
- High purity through controlled fermentation
- Decades of HA safety data support this class of treatment
- Low infection risk with proper sterile technique
- Repeatable - can be used for multiple treatment cycles
Allergy Safety: Key Advantage of Gelsyn-3
Safe for Bird and Egg Allergies
If you have allergies to eggs, chicken, poultry, or feathers, Gelsyn-3 is a safe option.
Why it matters:
Many older HA products (like Synvisc, Supartz, Orthovisc, Monovisc) are derived from chicken combs and may trigger allergic reactions in sensitive individuals.
Gelsyn-3 is produced through bacterial fermentation and contains no animal proteins, making it suitable for patients who:
- Have confirmed egg allergies
- React to chicken or poultry
- Want to avoid animal-derived products
- Need assurance of no cross-contamination
Other non-avian options include: Euflexxa, Durolane
Insurance Coverage and Cost
Medicare Coverage
Gelsyn-3 is covered by Medicare Part B when medically necessary criteria are met:
Step Therapy Protocols
Gelsyn-3 is often used in step therapy programs, where insurance requires trying certain treatments before authorizing others.
Typical step therapy hierarchy:
- First tier: Conservative treatment (PT, NSAIDs, weight loss)
- Second tier: Lower-cost HA products like Gelsyn-3, Supartz
- Third tier: Premium single-injection products (if step 2 fails)
- Final tier: Surgical options
Why insurers favor Gelsyn-3:
- Lower cost than single-injection alternatives
- Proven efficacy with strong research support
- Good safety profile means fewer complications
- Allows assessment of response before more expensive options
Out-of-Pocket Costs
| Scenario | Typical Cost |
|---|---|
| Without insurance | $500-$800 for full 3-injection course |
| With Medicare | 20% coinsurance after Part B deductible (~$75-$200) |
| With private insurance | Copay per visit × 3 visits (~$60-$150 total) |
| With prior authorization | May reduce or eliminate out-of-pocket cost |
Cost-saving tips:
- Ask about prior authorization to ensure coverage
- Check if your plan covers all three visits or requires separate copays
- Inquire about bundled billing to reduce administrative fees
- Some practices offer payment plans for uninsured patients
Gelsyn-3 vs. Other HA Options
Three-Injection Alternatives
| Brand | Source | Molecular Weight | Key Difference |
|---|---|---|---|
| Gelsyn-3 | Bacterial | Medium-high | Cost-effective, step therapy |
| Euflexxa | Bacterial | Low-medium | Similar non-avian option |
| Supartz FX | Avian | Low | 5 injections; not allergy-safe |
| Hyalgan | Avian | Low | 3-5 injections; older product |
Single-Injection Alternatives
| Brand | Source | Advantage | Trade-off |
|---|---|---|---|
| Durolane | Bacterial (Bioventus) | One visit; same company as Gelsyn-3 | Higher cost |
| Synvisc-One | Avian | Most widely used single shot | Not allergy-safe |
| Monovisc | Avian | High molecular weight | Not allergy-safe |
| Gel-One | Avian | Cross-linked formula | Not allergy-safe |
When to Choose Gelsyn-3
Choose Gelsyn-3 over single-injection products if:
- Your insurance requires step therapy
- Cost is a primary concern
- You prefer gradual delivery of treatment
- You can easily attend three appointments
Choose Gelsyn-3 over other three-injection products if:
- You have egg or poultry allergies
- You want a non-animal source
- Your insurance specifically covers it
- Your provider recommends it based on experience
Frequently Asked Questions
How long does each injection take?
The injection itself takes just a few minutes. With preparation, cleaning, and post-injection instructions, expect 15-20 minutes per appointment.
Can I drive myself to and from appointments?
Yes, most patients can drive themselves. Your knee may feel slightly stiff or sore, but it shouldn’t prevent driving.
Do the injections hurt?
Most patients describe mild-to-moderate discomfort during injection—similar to a flu shot. Your doctor may use numbing spray or local anesthetic to minimize discomfort.
What if I miss one of the three appointments?
Try to complete the series within the recommended weekly schedule. If you miss an appointment, contact your provider—they may adjust the schedule, but significant gaps may reduce effectiveness.
Can I get both knees treated at once?
It depends on your provider’s protocol. Some doctors treat both knees on the same day; others prefer to stagger treatment to monitor response and minimize temporary mobility limitation.
How soon can I return to exercise?
Light activity (walking) is encouraged within 24 hours. Moderate exercise (cycling, swimming) can typically resume within 1 week. High-impact activities (running, tennis) should wait 2-4 weeks or until symptoms improve significantly.
Will my insurance require prior authorization?
Many insurance plans do require prior authorization for HA injections. Your provider’s office typically handles this process, but it can take 3-7 days, so plan ahead.
Can I combine Gelsyn-3 with other treatments?
Yes, Gelsyn-3 can be part of a comprehensive approach including:
- Physical therapy
- Weight management programs
- Appropriate pain medications
- Activity modification
- Assistive devices (braces, orthotics)
How often can I repeat treatment?
If Gelsyn-3 provides relief that wears off after several months, you can typically repeat the treatment every 6-12 months as needed. There’s no limit to the number of courses you can receive.
Is Gelsyn-3 the same as Durolane?
Both are made by Bioventus and are non-avian HA products, but:
- Gelsyn-3 = 3 weekly injections, lower cost
- Durolane = 1 injection, higher cost, higher molecular weight
They’re both good options depending on your preference and insurance coverage.
Next Steps: Getting Gelsyn-3 Treatment
1. Confirm You’re a Candidate
Talk to your doctor about whether Gelsyn-3 is appropriate for your level of arthritis and overall health.
2. Verify Insurance Coverage
Contact your insurance provider to:
- Check if prior authorization is needed
- Understand your copay or coinsurance
- Confirm Gelsyn-3 is on your plan’s formulary
3. Schedule Your Appointments
Block out three consecutive weeks for your injection series. Try to schedule at the same time/day each week for consistency.
4. Prepare for Treatment
- Wear comfortable, loose-fitting pants or shorts
- Bring your insurance card and any authorization paperwork
- List all current medications
- Plan for light activity after each injection
5. Follow Post-Treatment Guidelines
- Apply ice as directed
- Avoid high-impact activity for 48 hours after each injection
- Attend all three appointments
- Report any concerning symptoms to your provider
Find Gelsyn-3 Providers
Locate knee specialists who offer Gelsyn-3 and can determine if this treatment is right for you.
Your information is secure. See our Privacy Policy and Terms of Service.
Thank You!
We've received your request. A provider specialist will contact you within 1-2 business days to help you find the right care.
What happens next?
- 1 We'll verify your insurance coverage
- 2 Match you with quality providers in your area
- 3 Contact you to discuss your options
Questions? Browse our guides:
How to Choose a ProviderThe Bottom Line
Gelsyn-3: Effective, Safe, Affordable
Gelsyn-3 offers a proven three-injection approach for knee osteoarthritis with several key advantages:
If you’re looking for a non-surgical treatment to manage knee pain and delay joint replacement, Gelsyn-3 deserves consideration—especially if you have allergies, need step therapy coverage, or prefer a gradual treatment approach.
Stay Informed About Knee OA Treatments
Get expert guidance on managing knee osteoarthritis with evidence-based treatment information.
Join 10,000+ readers. No spam.
Disclaimer
This information is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always consult your physician or qualified healthcare provider about any questions you may have regarding a medical condition or treatment options. Gelsyn-3 is a prescription product—discuss with your doctor whether it’s appropriate for you.
Last medically reviewed: January 15, 2025