New Possibilities for Cartilage Repair

Cartilage Treatment
Hyaline cartilage is known for its specific characteristics and combines a smooth surface and the ability to withstand extreme amounts of pressure. It is extremely important to reconstruct a perfect surface that will withstand heavy loads; unfortunately articular cartilage lesions, with their inherent limited healing potential, remains a challenging problem for orthopaedic surgeons.

In the last two decades, the trend has been to replace the articular surface when articular lesions become osteoarthritis; however, recent studies with the use of new orthobiological techniques in cartilage lesions have been used with increasing frequency and effectiveness as a way to regenerate neo-cartilage and retard progression of arthritis. Growth factors and mesenchymal stem cells have been used successfully in many medical fields such as maxillofacial, cosmetic, spine, orthopaedic and general wound healing applications. Gene therapy is also now being utilised to enhance the type of cartilage repair tissue.

Conservative Treatment
Non-surgical treatment of cartilage lesions, such as diet, intra-articular injections and rehabilitation, leads to pain control and activity modifications only. Focht et al.¹ analysed 316 obese adults and concluded that exercise and dietary weight loss resulted in improved mobility-related self-efficacy and pain reduction when compared with the healthy lifestyle control intervention.

Recent studies on pulsed electromagnetic fields (PEMFs) and platelet-rich plasma (PRP) injections have shown that these modalities have the capacity to assist cartilage tissue healing and hopefully retard osteoarthritis. In an animal study, Ciombor et al.² showed that PEMFs preserved the morphology of articular cartilage and slowed the development of osteoarthritic lesions in Hartley guinea pigs compared to a control group. They noted that electric and electromagnetic fields increase gene expression and the synthesis of growth factors. This may amplify field effects through autocrine and paracrine signalling. Electric and electromagnetic fields can produce a sustained up-regulation of growth factors, which enhance but do not disorganise endochondral bone formation. The authors concluded that PEMFs appear to be disease modifying in these populations.³

This was supported by Massari et al.,⁴ who summarised the results of the translational research of the Cartilage Repair and Electromagnetic Stimulation study group on the use of specific PEMFs, including I-ONE therapy, to control local joint inflammation and ultimately have a chondroprotective effect on articular cartilage (see Figure 1). Their study showed that in patients who underwent chondral coblation, three years later the number of patients who had completely recovered was higher in the group treated with I-ONE therapy compared to the control group. Clinical results show that I-ONE therapy is an effective chondroprotective treatment for patients immediately after arthroscopic surgery and does not have any negative side effects. It has a short-term effect in reducing the functional recovery time of patients.

Preventive Biological Solution
Recently the idea of a ‘biological solution for biological problems’ has led to the development of less invasive procedures and accelerated treatments that in general reduce morbidity while enhancing functional recovery. ⁵ One interesting therapy is PRP, which was first introduced by Ferrari et al. in 1987 in open heart surgery.⁶ Later this therapy enjoyed a great increase in popularity because of the versatility, biocompatibility and low costs of this approach. These factors have stimulated its therapeutic use in many medical fields.

Scientific research and technology has provided new insight in understanding the biological potential of platelets in wound-healing processes.^5,7 It is well known that platelets have many functions beyond simple hemostasis: platelets contain many important bioactive proteins and growth factors, such as platelet-derived growth factor, insulin-like growth factor, transforming growth factor (TGF-β), epidermal growth factor, fibroblast growth factor, vascular endothelial growth factor and others. These factors, when secreted, regulate key processes involved in tissue repair, including cell proliferation, chemotaxis, migration, cellular differentiation and extracellular matrix synthesis.^8,9

The rationale for topical use of platelet-enriched preparations is to stimulate the natural healing cascade and tissue regeneration by a ‘supra-physiological’ release of platelet-derived factors directly in the site of treatment. Several systems are available that prepare the PRP and the platelet gel: through these systems a two- to six-fold enrichment of platelet concentration is obtained, assuming a comparable growth factor enrichment (see Figure 2 and 3 ). The amount of growth factor available for tissue healing depends on the growth factors actually stored in platelets and the kinetics of the adsorption of the platelet gel. ¹⁰

Moreover, evidence is mounting to show that the crucial factors in the effectiveness of this treatment are the number of platelets used – at least 1.2–2.0 x 109/mL in PRP – and the way in which they are processed. This is because the growth factor content of the gel is highly sensitive to these two variables. ^7,11–14

Recent studies have documented the effectiveness of growth factors in chondrogenesis and prevention of degeneration of the joints.

Kon et al. ¹⁵ studied a group of 30 patients with symptomatic degenerative disease of the knee joints treated with three PRP intraarticular injections weekly. The follow-up at six months showed positive effects on function and symptoms, with an 85% improvement in scores for patients with a median age <60 years, while in patients >60 years improvement was only 30%.