**1. Introduction**

A two-decade long research has expedited knowledge about tissue repair mechanisms, and the field of Regenerative Medicine is gaining ground stimulated by novel insights and the development of therapeutic biotechnologies, intending to restore tissue architecture and functionality. Regenerative Medicine technologies concern not only traumatic tissue injuries but also involve the biological manipulation of pathological conditions aiming to drive tissue circumstances to normal, i.e. the recovery of tissue homeostasis.

Recent advances in biology and the new understanding of mechanisms such as angiogenesis, inflammation and main cell activities including proliferation, differentiation and metabolism have prompted researchers to seek how to manipulate these aspects of tissue and cell biology. Translation of this knowledge into the development of regenerative medicine technologies is imperative in order to address the current health care demand markedly boosted by demo‐ graphic changes. Indeed the dramatic increase in the economic and social burden of chronic and degenerative diseases urges the development of novel therapies.

Biological interventions in Regenerative Medicine fall into four main categories including gene therapy, tissue engineering, cell-based therapies, and platelet rich plasma (PRP) therapies, with different success in clinical translation. For example, tissue engineering approaches, i.e. cells loaded within scaffolds, are in development but still several limitations of 3D tissue constructs are unresolved; these questions include biocompatibility, improvements in mechanical properties and/or the size of the 3D constructs [1]. Similarly, the efficacy of different categories of cell therapies, including mesenchymal stem cells, embryonic stem cells or induced pluri‐ potent stem cells (iPSC), is being tested [2]. However, while registration of new clinical trials using MSCs derived from the bone marrow or from adipose tissue is growing rapidly supported by both public and private investments, the iPSC therapies are advancing at a slower

© 2015 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and eproduction in any medium, provided the original work is properly cited.

pace because reprogramming raises serious concerns about safety because of their genetic instability and potential to form tumors.

PRP, an autologous plasma fraction of peripheral blood, is the simplest regenerative medicine intervention that is rapidly extending to multiple medical fields mainly due to the easy use and biosafety that facilitates translation in humans. In fact, regulatory requirements for cell therapy involve multiple preclinical experiments to demonstrate their safety and nonteratogen effects in addition to GLP compliance in the preparation, and the use of adequate expensive installations [3]. In contrast, PRP therapies involve minimal manipulation, and in general, regulatory requirements are easy to comply thereby facilitating the widespread clinical use and commercial success of PRP kits and devices. In fact, PRP can be prepared by using any of the commercial systems available. PRPs can also be prepared by in house procedures, providing that basic rules of quality are implemented.

While regenerative medicine with cells is directed to inherent non-healing problems and a wide range of pathological conditions, PRP embrace normal healing conditions such as tissue repair during surgical invasion or traumatic injuries seeking to enhance and accelerate physiological repair. Alternatively, PRPs as occurs with cell therapies, seek to direct nonhealing conditions, e.g. chronic conditions such as osteoarthritis (OA) or tendinopathy, towards healing and restoration of tissue homeostasis.

Due to the biosafety of these products, i.e. advantageous balance risk-benefit, clinical appli‐ cations have preceded the basic research. Actually, in its very beginnings PRPs have been used with a vague idea of the biological mechanisms they were influencing. Thereafter, most studies were directed to examining clinical outcomes rather than identifying the precise biochemical mechanisms underlying PRP effects, which remain to be elucidated in the most part. In fact, PRP widespread use was not driven by the principles of the scientific methods instead patient demand has been boosted by sports news and propaganda reporting that outstanding elite athletes had been successfully treated with PRP. The need is clear, to investigate and describe main PRP targets and action mechanisms underlying their clinical effects. In fact, translational medicine addresses both, the biological and the clinical aspect of the novel biotechnologies.

In this book chapter, first, we will discuss recent progress on understanding the tissue regeneration process with a particular focus on the healing stages, and the role of PRP released signaling proteins in targeting different cells and inducing paracrine actions. Current biolog‐ ical interventions aiming tissue regeneration stem from two concepts, namely cells responsible for tissue homeostasis, and the signaling cytokines that control cell fate. Several cell pheno‐ types are involved in tissue repair and some processes such as inflammation and angiogenesis are commonly involved in the repair process in several conditions. Hence, several notions of tissue repair mechanisms are compatible with the biological hallmarks of regeneration in different tissues. Common mechanisms involved in healing can be modulated using PRP. This is the basic knowledge to drive clinical applications.

Second, from a practical point of view on PRP biotechnology we will discuss the main formulations, and summarize commercial systems to prepare PRP. Regulatory requirements will be briefly exposed.

Lastly, we will focus on translational uses, that is to say current PRP interventions from the clinical investigation perspective. We will summarize PRP applications in surgery with special emphasis in novel developments, the current use of PRP in ulcers, ophthalmology and dermatology, as well as foremost conservative treatments in orthopedics and sports medicine.

We will discuss main obstacles for the advancement of PRP science and future perspectives.
