PRP & Knee Osteoarthritis: why quality matters more than quantity

Influence of platelet count on the clinical effectiveness of platelet-rich plasma in the treatment of knee osteoarthritis: A systematic review and meta-analysis

For years, platelet-rich plasma (PRP) has become an important option in regenerative medicine, particularly in the management of knee osteoarthritis (gonarthrosis). Yet one persistent belief remains widespread: the more platelets PRP contains, the more effective it will be.

The latest data show the opposite. A systematic review and meta-analysis published in 2025 by Simental-Mendía et al. in Orthopaedics & Traumatology: Surgery & Research analysed 43 randomised controlled clinical trials evaluating PRP in knee osteoarthritis.

3

Key Finding: Moderate Platelet Concentration (≤4×) Is Clinically Superior

 

The authors report that

  • PRP formulations with a moderate platelet concentration factor (≤4× baseline) offer the strongest and most consistent improvements in pain and joint function.

  • Highly concentrated PRP (>4× baseline) does not provide additional clinical benefit and may even dampen the biological response.

In other words, in PRP therapy for knee osteoarthritis, “more” is not automatically “better”. The best results are obtained when platelet concentration respects joint tissue physiology rather than maximising numbers at all costs.

2

Why More Is Not Always Better: The Biological Explanation

The idea that “more platelets = more healing” feels intuitive – but it does not match what we know about tissue biology.

When over-concentration becomes counterproductive

Beyond a certain threshold, excessively high platelet concentration can: 

  • Saturate receptors on target cells, so additional growth factors no longer translate into more activity.

  • Disrupt cytokine balance, tipping the environment towards an unfavourable inflammatory profile.

  • Trigger inhibitory feedback, limiting tissue regeneration and potentially compromising the quality of the repair.

The result:

  • Clinical response is not improved, despite higher platelet counts.

  • The quality and coherence of the regenerative process may be reduced.

The optimal therapeutic window for PRP in knee osteoarthritis therefore sits around a moderate platelet concentration factor ≤4×, where the biological signal remains balanced and compatible with the physiology of joint tissues.

From Controversy to Clarity: Standardisation Is the Real Issue

Much of the debate around PRP does not question the concept of autologous platelet-based therapy itself. It reflects the large variability in PRP preparations:

  • Different blood volumes

  • Very different platelet concentration factors

  • Variable leukocyte content

  • Diverse activation methods and timings

The Simental-Mendía analysis makes this clear: inconsistent results in the literature are mainly linked to heterogeneous preparation protocols, not to PRP as a therapeutic principle.

The key question is not whether PRP works, but how it is prepared.

Why standardisation changes everything

When:

  • Platelet concentration,

  • Leukocyte content, and

  • Activation methods

are controlled and aligned with tissue physiology, PRP:

  • More reliably shows superior clinical outcomes compared with several other treatment options for knee osteoarthritis.

  • Becomes a predictable and reproducible tool in everyday practice, rather than an “artisan” product with variable composition.

|

Confidence in PRP therefore starts with confidence in its preparation.

|

The Biology of Precision: Why a Moderate Platelet Count Is Optimal

The meta-analysis confirms a simple biological principle: regeneration depends on balance, not excess

With a platelet concentration factor ≤4× baseline, PRP releases optimal levels of key growth factors such as PDGF, TGF-β and VEGF, supporting:

  • Anti-inflammatory pathways

  • Tissue repair and matrix synthesis

  • Neo-vascularisation and functional joint recovery

When this threshold is exceeded:

  • Biological signalling can become disorganised.

  • Receptor saturation and excessive cytokine activity may limit regeneration.

  • Clinical response tends to be less consistent and less predictable.

The effectiveness of PRP is therefore not a “race for growth factors”, but the result of a controlled signal, adapted to the sensitivity of joint tissues.

Regen Lab: Standardised PRP Designed to Respect Tissue Physiology

For over two decades, Regen Lab has promoted a clear principle in regenerative medicine: quality matters more than quantity.

A PRP formulation optimised by design – not by chance

Regen Lab medical devices are engineered to produce a standardised, leucocyte-reduced PRP with an optimised formulation, in line with clinical and biological data:

  • Moderate platelet concentration factor (typically ≤4× baseline), in line with evidence from knee osteoarthritis studies.

  • Controlled key parameters (platelets, leukocytes, activation) for consistent PRP quality.

  • Reproducible PRP composition, ideal for evidence-based protocols and multi-centre use.

This approach aims to:

  • Reduce inter-patient and inter-operator variability.

  • Improve the reliability of clinical results.

  • Support high-quality practice in orthopaedics and regenerative medicine.

An international reference in autologous regenerative therapies

  • Over 20 years of research and development

  • Validated, CE-marked medical devices

  • International regulatory compliance

Regen Lab contributes to defining the standard for standardised PRP, bringing together science, safety and day-to-day clinical practicality.

What This Changes in Everyday Clinical Practice

PRP, platelet concentration and knee osteoarthritis

For healthcare professionals treating knee osteoarthritis, these findings have very practical implications: regenlab.fr+1

1. Rethink the target platelet concentration
  • Prioritise PRP systems delivering a moderate platelet concentration factor (≤4×).

  • Avoid the temptation of “over-concentration”, which does not improve outcomes and can compromise tissue regeneration.

2. Demand standardisation
  • Choose devices that guarantee a reproducible composition (platelet concentration, leukocyte reduction, activation).

  • Reduce the impact of preparation variability on clinical outcomes.

  • Align your practice with evidence-based regenerative medicine.

3. Strengthen trust with patients
  • Explain that PRP is not an improvised product, but a therapy that must be prepared according to precise standards.

  • Support patient discussions with high-level publications, such as the 2025 Simental-Mendía meta-analysis on PRP and knee osteoarthritis.

FAQ

PRP, Platelet Concentration and Knee Osteoarthritis

Is a more concentrated PRP always more effective?

No. Data from the meta-analysis show that highly concentrated PRP (>4× baseline) does not improve clinical outcomes and may attenuate the biological response. The best results for pain and function are associated with moderate platelet concentration (≤4×).

Why is PRP standardisation so important?

Because PRP outcomes depend directly on the quality and consistency of the preparation. Non-standardised formulations are a major cause of inconsistent results across certain trials. Standardised PRP reduces variability and makes results more predictable in daily practice.

What exactly did the Simental-Mendía et al. (2025) study show?

This systematic review and meta-analysis of 43 randomised controlled trials on PRP in knee osteoarthritis concluded that:

  • Moderate platelet concentration (≤4× baseline) is associated with the best clinical outcomes.

  • Higher platelet concentrations do not provide additional benefit and may be biologically counterproductive.

3

The Bottom Line: Trust in PRP Begins with Trust in Its Science

About Us

Since 2003, Regen Lab SA has specialized in designing and manufacturing high-quality medical devices for cell therapies and the preparation of autologous platelet-rich plasma (PRP) from the patient's own blood for bedside procedures.

Milestones

2003 - Foundation
2010 - RegenKit first approval in bone graft
2013 - A new state-of-theart laboratory in Lausanne
2014 - Cellular Matrix first approval
2015 - Launch of Cellular Matrix in Europe

Vision

Founded in 2003, Regen Lab has become a global reference thanks to its commitment to innovation, quality, and the effectiveness of its therapeutic solutions. Here’s how we have transformed the medical landscape over the past two decades.

RegenPRP™

RegenPRP™ is a medical treatment that uses platelet-rich plasma from the patient's own blood to enhance and tissue regeneration.

RegenPRP™ - HA

RegenPRP™ - HA combination is an innovative treatment combining platelet-rich plasma (PRP) and hyaluronic acid to improve tissue regeneration and healing.

RegenPRP™ - ATS

RegenPRP™ combined with ATS (Autologous Thrombin Serum) is an advanced approach to tissue regeneration that uses autologous thrombin-enriched platelet-rich plasma (PRP) to maximise healing effects.

RegenExtracell®

RegenExtracell is an innovative tissue regeneration treatment using an extracellular matrix enriched with platelet-rich plasma (PRP).

Hyaluronic Acid

Coming Soon

Regulatory

Manufacturers of medical devices based outside the EU must designate an Authorized Representative (EU-REP) established within the EU in order to meet the CE requirements for placing medical devices on the EU market.

Quality Management

Regen Lab Quality System Management ensures the consistency of our products quality in total GMP compliance.

Our production facility rooms atmosphere is monitored to satisfy non-pyrogenic medical devices manufacturing.

Patents

As a leader in the PRP&HA regenerative field and as an innovation-driven company, Regen Lab SA has devoted important resources since 2004 to put on the market pioneering and diversified products constituting a complete set of tools/technologies for the medical community.