**6. Challenges ahead**

As PRP is eminently a translational technology, challenges must be addressed through three interlinked angles: scientific, clinical and socioeconomic.

From the scientific aspect, evidence continues to build for the mechanisms of PRP in tissue repair regulating the behavior of different cell types. At present we have a more complete picture on how PRP influences healing mechanisms however, we do not know enough to design formulations for specific medical problems. Difficulties to advance are attributed to the lack of characterization of the host tissue. In fact, the host response to PRP administration will drive the healing mechanisms. The host response invariably starts with activation of the immune innate system as a result of PRP administration. Moreover, considering the local pH, O2 levels, and cellular conditions of the host (i.e. number of dying cells apoptotic or necrotic) is important not only in terms of GFs and cytokine stability but also to have information about the main mechanism affected.

Clinical challenges: PRP research may eventually lead to superior therapies. The translational imperative is making PRP formulation effective in defined indications. The challenge is to customize PRP formulations. Essentially a single formulation cannot fulfill every need, from treating a degenerative knee to repairing a pseudo-arthritic condition.

The modest benefits achieved with clinical trials addressing PRP efficacy should not reduce our motivation, instead we need to understand better the underlying mechanisms so that the most appropriate indications can be found and appropriate trials conducted to test the specific indications. Novel approaches to clinical trial design shall recognize that the efficacy of these therapies will be dependent upon delivery protocol as well as the PRP product itself.

Socioeconomic challenges: we should consider carefully the potential of PRPs to reduce costs in chronic diseases. This could be achieved by the creation of proper registries and economic models considering the costs generated in pre-treatment run-in periods. In patients with recalcitrant pathologies, candidates to surgical interventions, economical algorithms will help to estimate savings attributable to surgical and post-surgical costs relative to the conservative management.


\*\*\* Broadly used, that is RCTs, several clinical evidences and different levels of evidence

\*\* Moderate use, case series and at least one controlled study

\* Anecdotic use, case series or an isolated prospective cohort

**Table 3.** Miscellaneous applications of PRPs in open surgery


**Eye disease**

In a prospective controlled study in acute ocular chemical injury PRP eyedrops as adjunct to standard care was superior to artificial tears, autologous platelet lysate was also effective for

Some anecdotic uses of PRP in urology for fistula repair [84], in the management of infantile extravasation injury [85], and in gynecology for vaginal prolapse [86-87] have been published.

As PRP is eminently a translational technology, challenges must be addressed through three

From the scientific aspect, evidence continues to build for the mechanisms of PRP in tissue repair regulating the behavior of different cell types. At present we have a more complete picture on how PRP influences healing mechanisms however, we do not know enough to design formulations for specific medical problems. Difficulties to advance are attributed to the lack of characterization of the host tissue. In fact, the host response to PRP administration will drive the healing mechanisms. The host response invariably starts with activation of the immune innate system as a result of PRP administration. Moreover, considering the local pH, O2 levels, and cellular conditions of the host (i.e. number of dying cells apoptotic or necrotic) is important not only in terms of GFs and cytokine stability but also to have information about

Clinical challenges: PRP research may eventually lead to superior therapies. The translational imperative is making PRP formulation effective in defined indications. The challenge is to customize PRP formulations. Essentially a single formulation cannot fulfill every need, from

The modest benefits achieved with clinical trials addressing PRP efficacy should not reduce our motivation, instead we need to understand better the underlying mechanisms so that the most appropriate indications can be found and appropriate trials conducted to test the specific indications. Novel approaches to clinical trial design shall recognize that the efficacy of these

Socioeconomic challenges: we should consider carefully the potential of PRPs to reduce costs in chronic diseases. This could be achieved by the creation of proper registries and economic models considering the costs generated in pre-treatment run-in periods. In patients with recalcitrant pathologies, candidates to surgical interventions, economical algorithms will help to estimate savings attributable to surgical and post-surgical costs relative to the conservative

therapies will be dependent upon delivery protocol as well as the PRP product itself.

treating a degenerative knee to repairing a pseudo-arthritic condition.

the treatment of refractory ocular GVDH in unresponsive patients [83].

interlinked angles: scientific, clinical and socioeconomic.

*5.5.4. Other therapeutic applications*

**6. Challenges ahead**

22 Biotechnology

the main mechanism affected.

management.


**Table 4.** Conservative clinical applications of PRP therapies
