THE CELLULAR MATRIX® REVOLUTION FOR THE TREATMENT OF GONARTHROSIS: FROM HYALURONIC ACID VISCOSUPPLEMENTATION TO COMBINATION WITH PRP.

Philippe ADAM MD., Marine DELCROS, MD – RegenLab

P. Adam naturally turned to osteoarticular pathologies. He is a radiologist at the Médipôle Garonne clinic in Toulouse, a former reserve lieutenant physician (ENORSSA Libourne) and a former head of clinic at the Toulouse University Hospital. A graduate in Aeronautical and Space Medicine (Toulouse-France), he is also heavily involved in sports medicine (expert for the French National Rugby League).

A member of SIMS (Société d’Imagerie Musculo-Squelettique) and ICRS (International Cartilage Repair Society), and a founding member of GRIIP (Groupe de Recherche International sur les Injections de Plaquequettes), P. Adam currently follows over 7,000 patients with gonarthrosis, and has been interested for several years in intra-articular, ultrasound-guided injectable products and their therapeutic combinations.

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INTRODUCTION

• Intra-articular injection of hyaluronic acid (HA) has been used for years for Kellgren & Lawrence grades I to III of symptomatic gonarthrosis, thanks to the product’s viscoelastic and lubricating properties.

• Platelet-rich plasma (PRP), for its part, has biological analgesic and anti-inflammatory effects, not to mention its main role in the release of growth factors, which enable the activation of chondrocytes and other mesenchymal stem cells.

• HA can also be likened to a biological network, helping growth factors to reach their receptors. It has the ability to retain PRP, thereby prolonging its effects, notably on platelet residence time and cell migration.

• The PRP-HA combination is proposed after failure of other treatments (including HA alone). It reduces cartilage catabolism and the inflammation that accompanies osteoarthritis.

• It also has a synergistic action on chondrogenesis, as described in numerous in vitro studies
[2, 3, 4], suggesting that PRP + HA are more effective than HA or PRP alone.

• It’s not just a question of simple complementarity, but of a definite synergy, a real “add-on effect”.

Indications for Cellular Matrix A-CP HA (Regenlab®) in symptomatic stage II and III gonarthrosis

Thus, the coupled injection of PRP-HA was tested with efficacy and safety on symptomatic stage II and III gonarthrosis patients in 2015.

Injection of 2 mL LP-PRP + 2 mL non-cross-linked HA (Cellular Matrix A-CP HA RegenLab®) shows clinical results superior to intra- articular infiltration of PRP alone (4-5 mL).

HA acts as a matrix, or network, protecting the PRP [1]. It’s more like a “super-PRP” than a “super-hyaluronic acid”.

The effects of the PRP-HA combination are even superior to both PRP or HA alone, in particular Sinovial Forte® 1.6% [5] in terms of pain and functionality, at 3, 6 and 12 months [6, 7, 8, 9]. Moreover, PRP does not alter the viscosupplementation properties of HA [10].

It is important to pay particular attention to PRP and hyaluronic acid combinations performed as separate injections, which in this case are not authorized

EQUIPMENT AND METHOD

The product Cellular Matrix A-CP- HA (Regenlab®)

Cellular Matrix A-CP- HA (RegenLab®) is a non-cross-linked LP-PRP + HA combination (2% concentrated bacterial origin). It is a class III device.

P. ADAM PERFORMED 7,124 CELLULAR MATRIX INTRA-ARTICULAR INFILTRATIONS (80% GONARTHROSIS), BETWEEN THE END OF 2012 AND THE END OF 2023, IN PATIENTS WITH SYMPTOMATIC GONARTHROSIS, BILANTES ON IMAGING (RADIOGRAPHY BEING A MAJOR ELEMENT).

• Cellular Matrix® is particularly adapted for large joints, with smaller joints benefiting from PRP alone.

• For the most part, patients come to us after other therapies have failed, including correction of contributing factors, cortisone infiltration and, above all, visco-supplementation, for which the notion of
«escape phenomenon» must be emphasized.

• This raises the question of whether Cellular Matrix should be indicated as a first-line treatment, in order to avoid such failures and to achieve a faster, more cost-effective long-term result.

• P. Adam recommends maintaining a close relationship with patients, communicating with them by e-mail throughout the follow-up, and standardizing procedures: a follow-up at 6 weeks, then at 3 months, is always combined with rehabilitation advice. Patients are also informed in advance with flyers explaining the products, their effects and the application process.

TECHNICAL

Infiltration is performed after ultrasound examination of a non-congestive knee, using a lateral approach. As head of the Pain Management Group for GRIIP, Adam urges puncture prior to infiltration, in the case of a congestive knee (or the presence of a popliteal cyst).

Based on this experience, he favors a single infiltration of Cellular Matrix®, with a second infiltration at 6 months, 2 or 3 years, depending on results.

Managing rigorous asepsis (masks, cap, gel and sterile gloves), and of course the risk of bleeding, is an inherent part of medical practice, and is explained to the patient in consultation.

DISCUSSION

A HA concentration of less than 1% showed a clear decrease in the mixture’s viscoelastic properties, and no effect on chondrocyte proliferation in vitro [10].

Molecular weight and the type of HA used are therefore very important.
Studies are underway with a combination of LP-PRP + cross-linked HA (RegenMatrix®, RegenLab®), compared with infiltration with Synvisc-One® or placebo (saline solution).

Another promising avenue is the combination of PRP (RegenPRP®) with an autologous thrombin preparation (RegenATS), to form a leukocyte-poor platelet gel with the dual benefit of filling and prolonged growth factor release.

P. Adam also observed astonishing results on rotator cuff and lateral epicondyle tendinopathies for the upper limb, and on posterior tibial, patellar and calcaneal tendinopathies for the lower limb.

CONCLUSION

PRP continues to deliver convincing clinical results.

We must not forget to integrate the evolution of the pathology into the reasoning and prevention of this same evolution: it is essential to treat the precursor factors of gonarthrosis.

In addition, networking is essential: from the technical sales representative to the contrast agent supplier, for example, the benefits for everyone are indisputable.

Finally, it’s important to keep patients informed, to make medical correspondents aware of the undeniable benefits of the combination of platelet-rich plasma and hyaluronic acid, and to pass on the message that good clinical practice must be respected.

REFERENCES

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2. Sundman EA, Cole BJ, Karas V, Della Valle C, Tetreault MW, Mohammed HO, Fortier LA. The anti-inffammatory and matrix restorative mechanisms of platelet-rich plasma in osteoarthritis. The American journal of sports medicine. 2014;42(1):35- 41.
3. Chen WH, Lo WC, Hsu WC, Wei HJ, Liu HY, Lee CH, et al. Synergistic anabolic actions of hyaluronic acid and platelet-rich plasma on cartilage regeneration in osteoarthritis therapy. Biomaterials. 2014;35(36):9599-607.
4. Satin AM, Norelli JB, Sgaglione NA, Grande DA. E ect of Combined Leukocyte-Poor Platelet-Rich Plasma and Hyaluronic Acid on Bone Marrow-Derived Mesenchymal Stem Cell and Chondrocyte Metabolism. Cartilage. 2021;13(2_suppl):267S- 76S.
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9. Renevier JL, Marc JF, Adam P, Sans N, Le Coz J, Prothoy I. “Cellular matrix™ PRP-HA”: A new treatment option with platelet-rich plasma and hyaluronic acid for patients with osteoarthritis having had an unsatisfactory clinical response to hyaluronic acid alone: Results of a pilot, multicenter French study with long-term follow-up. Int J Clin Rheumatol. 2018;13(4):230-8.
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