Viscosupplementation is a modern method for treating degenerative joint disease involving intra-articular injection of hyaluronic acid (HA) – a natural component of synovial fluid. At our Centre we use the highest quality HA preparations from bacterial biofermentation: REGENFLEX Bio-Plus, REGENFLEX Starter and SYNOZ Ultra. Each has its specific indications depending on molecular weight and rheological characteristics.

  • REGENFLEX Bio-Plus 75 mg / 3 ml (HMW HA + sodium salt)
  • Regenflex Starter 32 mg / 2 ml (hyaluronic acid)
  • SYNOZ Ultra 75 mg / 3 ml (HMW HA, biofermentation)

Hyaluronic Acid in the Joint – Mechanism of Action

Hyaluronic acid is a natural polysaccharide present at high concentration in healthy synovial fluid, where it acts as a lubricant, shock absorber and carrier of biochemical information. In a degenerated joint, its concentration and molecular weight fall significantly, leading to loss of the lubricating and protective properties of the synovial fluid. Exogenous HA administered intra-articularly acts on multiple levels:

  • MECHANICAL EFFECT – restores the viscoelasticity of synovial fluid, facilitates gliding of articular surfaces, absorbs loads, reduces cartilage friction
  • BIOLOGICAL EFFECT via CD44 RECEPTOR – HA binds to the CD44 receptor on chondrocytes and synoviocytes, inhibiting expression of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) and matrix metalloproteinases (MMP-1, MMP-3, MMP-9, MMP-13) responsible for cartilage degradation
  • CHONDROPROTECTIVE EFFECT – stimulates endogenous synthesis of HA, proteoglycans and type II collagen by chondrocytes (anabolic effect)
  • ANTI-INFLAMMATORY EFFECT – reduces PGE2 and nitric oxide (NO) concentrations in the synovial membrane, decreases cellular infiltration in synovial fluid
  • ANALGESIC EFFECT – coats the pain fibre C-endings in the joint capsule, blocking pain receptors

Key principle: HIGH MOLECULAR WEIGHT = GREATER EFFICACY. High molecular weight HA (HMW HA, >1,500 kDa) has a stronger affinity for the CD44 receptor, remains in the joint longer and better inhibits pro-inflammatory cytokines. Low molecular weight HA (LMW HA, <400 kDa) may actually activate the pro-inflammatory pathway via TLR (Toll-Like Receptors) – hence we prefer high molecular weight preparations.

REGENFLEX Bio-Plus 75 mg/3 ml – High Molecular Weight HA with Sodium Salts

REGENFLEX Bio-Plus is a concentrated preparation containing 75 mg hyaluronic acid in 3 ml (25 mg/ml concentration), produced by bacterial biofermentation (NEAPS – Non-Avian Animal Free Production System), without the allergy risk associated with preparations derived from rooster combs. It is characterised by high molecular weight, long joint residence time and good rheological properties. Indications: degenerative disease of large joints (knee, hip, shoulder), Kellgren-Lawrence grades 2–3. Most commonly used as 1–3 injections at weekly intervals, with an effect lasting 6–12 months.

Regenflex Starter 32 mg/2 ml – for Small Joints and Initial Therapy

Smaller concentration (16 mg/ml) and smaller volume (2 ml) – ideal for small joints (temporomandibular, small hand and foot joints, elbow, wrist) or as initial therapy in patients with less advanced changes. The favourable cost allows comprehensive treatment of multiple joints.

SYNOZ Ultra 75 mg/3 ml – HMW HA from Biofermentation

A high molecular weight preparation produced by biofermentation – safe and effective in treating degenerative disease of large joints. Represents a cost-effective alternative to premium preparations while maintaining the full chondroprotective and anti-inflammatory action profile.

Indications for Viscosupplementation

  • Knee joint degenerative disease (gonarthrosis) – the best-documented indication – ultrasound guidance
  • Coxarthrosis – hip joint degenerative disease (under X-ray or ultrasound guidance)
  • Shoulder joint degenerative disease – ultrasound guidance
  • Degenerative changes of small hand joints (e.g. thumb)
  • Temporomandibular joint (TMJ) dysfunction and degeneration
  • Chronic ankle, elbow and wrist joint pain
  • Patients in whom arthroplasty is to be avoided or deferred
  • Patients with contraindications to long-term NSAID therapy (gastric, renal, cardiovascular problems)
  • Supporting rehabilitation after joint injuries

Procedure Sequence

  • Qualifying consultation with X-ray and/or ultrasound assessment of the joint, establishing indications and selecting the preparation.
  • Patient in a comfortable position, skin disinfection, sterile field.
  • Always under ultrasound guidance – for large joints: knee, shoulder, hip; or small joints – a fine 22–25G needle is introduced precisely into the joint cavity.
  • In case of joint effusion – fluid aspiration (improves HA efficacy).
  • Slow administration of the HA preparation (75 mg in 3 ml or 32 mg in 2 ml).
  • Brief joint massage after injection – even distribution of the preparation.
  • The entire procedure takes 5–10 minutes. After the procedure the patient may return to normal activity (except intense sport for 24–48h).

Treatment Schedule

  • Classic protocol: 1 injection per week for 3 weeks (3 injections total)
  • Modern HMW preparations: often 1 injection is sufficient, repeated every 6–12 months
  • In patients with advanced changes: cycle of 3 injections every 6 months
  • Can be combined with PRP (e.g. Arthrex ACP) or steroid for enhanced effect

Effects

  • First improvement: 2–4 weeks after the first injection
  • Full effect: 6–8 weeks after completing the cycle
  • Duration of effect: 6–12 months (HMW HA), 3–6 months (LMW HA)
  • Pain reduction of 30–60% measured on the WOMAC scale
  • Improvement in joint function, increased range of motion
  • Reduced requirement for NSAIDs and analgesics
  • Possibility of deferring arthroplasty by 2–5 years in well-responding patients
  • Best results when combined with physiotherapy, weight reduction and load modification

Possible Side Effects

  • Transient joint pain and stiffness (24–72h after the procedure) – resolves spontaneously
  • Minor joint swelling
  • Post-injection flare reaction (rare, up to a few days)
  • Very rarely: allergy (especially with rooster comb-derived preparations – in our biofermentation preparations the risk is minimal)
  • Very rarely: joint infection (strict aseptic technique is maintained)

Contraindications

  • Active skin infection near the joint or systemic infection
  • Active joint inflammation of unclear aetiology (requires diagnostic work-up)
  • Advanced degenerative joint disease (K-L grade 4) – arthroplasty is likely more effective
  • Hypersensitivity to hyaluronic acid
  • Pregnancy (insufficient safety data)

FAQ

What is the difference between REGENFLEX Bio-Plus, Starter and SYNOZ Ultra?

REGENFLEX Bio-Plus and SYNOZ Ultra are high molecular weight (HMW) preparations at 25 mg/ml concentration, used for large joints with advanced changes. Regenflex Starter is a smaller volume preparation (2 ml), ideal for small joints or initial therapy. The choice depends on the joint, degree of disease progression and the patient’s budget preference.

Will viscosupplementation replace arthroplasty?

In patients with moderate changes (K-L grade 2–3) it may defer arthroplasty by 2–5 years or longer, especially in combination with physiotherapy and lifestyle modification. In grade 4 (advanced changes, absent cartilage) surgery is usually more effective.

How often can HA injections be repeated?

For HMW HA (REGENFLEX, SYNOZ) – every 6–12 months. There are no strict limits on the number of cycles if each one is effective.