**5. Conclusions**

*Regenerative Medicine*

of homeostasis and in the pathophysiology of joint degeneration [17]. In order to extend the range of action of the PRP and also act on the subchondral bone, Sánchez et al. described the technique of PRP intraosseous infiltrations (**Figure 5**). This method of application combines conventional intra-articular injection of PRP with intraosseous infiltrations into the subchondral bone of the femoral condyle and tibial plateau in severe cases of knee OA [90]. Afterward, this technique was adapted to treat advanced cases of hip OA, combining intra-articular infiltration with intraosseous infiltrations into the femoral head and acetabulum [91]. In both cases, intraosseous administration must be assisted by imaging, ultrasound, or

*Intraosseous administration of PRP. Intraosseous PRP administrations allow the subchondral bone to be reached and its therapeutic effect to be extended. Intraosseous infiltrations are applied in the femoral condyle (A) and tibial plateau (B) in patients with knee OA and in the acetabulum (C) and femoral head (D) in cases of hip OA.*

The first published works carried out using this technique provided promising results. In a pilot study performed with patients who presented knee OA of grades 3 and 4 according to the Ahlbäck scale, pain was significantly reduced, and an increase in joint function was observed at 6 months after receiving the combination of intra-articular and intraosseous PRP injections. In addition, the number of MSCs present in the synovial fluid decreased after this treatment [92]. This finding was not observed in patients treated only with intra-articular infiltrations, suggesting the importance of the subchondral bone in the modulation of cellular response in joint degeneration [74]. Following the same trend, an observational study compared the intra-articular administration of PRP versus the combination of intra-articular and intraosseous injections in patients with severe knee OA. The results of this study showed that although there was no difference between both groups at 2 months after treatment, patients who received the PRP intraosseously showed clinically superior results at 6 and 12 months [93]. Su et al. conducted a

fluoroscopy, to ensure correct delivery in the required area.

**82**

**Figure 5.**

Joint degeneration is a pathology that affects a large part of the population, deteriorating their quality of life being disabling in many cases. It is also related to aging and unhealthy lifestyle habits; thus it is expected that its prevalence will increase in the coming years, assuming a great cost to health systems. Current conventional treatments focus on symptomatic relief without addressing the cause of the disease. Because of this, new treatments based on regenerative medicine are emerging in order to expand the therapeutic arsenal and delay or prevent joint replacement, which is currently the only definitive solution for patients. Moreover, in order to achieve an optimal treatment for joint degeneration, it must be understood that the joint works as a whole organ. All elements of the joint participate in the maintenance of homeostasis, the synovial membrane, cartilage, and subchondral bone being key for biological balance.

This balance could be maintained or restored by means of several biological therapies such as PRP that is a cocktail of plasma and platelet biomolecules, and it is obtained after fractionating small blood volumes by centrifugation. PRP has a great versatility since it allows its use through different types of formulations, being able to be applied both in outpatient infiltrations and surgical interventions. The therapeutic potential of PRP in joint degeneration lies in its ability to modulate inflammation, lubrication, and pain, acting on different cell populations to create a biological environment conducive to tissue repair. However, the variety in the composition of PRP products leads to different biological effects and consequently contradictory clinical results. It is, therefore, necessary to identify and characterize the PRP used in order to advance both research and clinical practice.

The success of the PRP also depends on the method of clinical application. The administration of PRP has to cover the main joint tissues so that the biological effects of PRP act over the cells of in order to reverse the course of the pathology. Although the safety and ease of obtaining PRP have allowed a quick transfer from the laboratory to the hospital, much is still unknown about this therapy, and further basic and clinical research is needed.

*Regenerative Medicine*
