Platelet-rich plasma and its derivatives as promising bioactive materials for regenerative medicine: basic principles and concepts underlying recent advancesby Tomoyuki Kawase



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Platelet-rich plasma and its derivatives as promising bioactive materials for regenerative medicine: basic principles and concepts underlying recent advances

Tomoyuki Kawase1,2

Received: 23 January 2015 / Accepted: 16 May 2015  The Society of The Nippon Dental University 2015

Abstract Over the past decade, platelet-rich plasma (PRP), a platelet-concentrated plasma fraction, has been widely investigated and applied to regenerative medicine.

The clinical utility of PRP is supported by evidence that

PRP contains high concentrations of platelet-related growth factors and normal concentrations of plasmaderived fibrinogen, both of which contribute synergistically to the regenerative process. Additionally, its superior costefficacy versus conventional therapies is attractive to many clinicians. However, current disadvantages of PRP include a relatively complicated preparation procedure and variable operator-dependent efficacy. An additional disadvantage is the use of bovine thrombin, an animal-derived biological, as a coagulant. Many of these disadvantages are overcome by recent advances in preparation procedures and devices; for example, Joseph Choukroun simplified the platelet-rich fibrin preparation procedure and improved handling efficiency without the aid of animal-derived factors. With advancements in cell processing technology, there has been a general shift in cell therapy from autologous to allogeneic treatment; however, autologous PRP therapy will not easily be replaced by allogeneic treatment in the near future.

Therefore, to provide more predictable regenerative therapy outcomes using autologous PRP, further investigations should address developing a standardized procedure for

PRP preparation to augment its efficacy and potency, independent of donor variability. We would then propose that operators and clinicians prepare PRP according to the standardized protocol and to carefully evaluate the clinical scenario (i.e., recipient factors comprising skeletal defects) to determine which factor(s) should be added to PRP preparations. This careful approach will lead to improved clinical outcomes for patients.

Keywords Platelet-rich plasma  Platelet-rich fibrin 

Quality control  Standardization  Regenerative medicine


Platelet-rich plasma (PRP) is a platelet-concentrated plasma fraction. As demonstrated in previous studies [1–6], growth factors derived from platelets are present and concentrated in PRP preparations (Table 1). By contrast, growth factors derived from other cell lineages, such as colony-stimulating factors and hepatocyte-growth factors, as well as plasma-derived components such as albumin and fibrinogen, are not as concentrated. Recently, PRP has been increasingly used for the regeneration and reconstruction of skeletal and connective tissues in the periodontal and maxillofacial fields [7, 8]. In this review article, we present recent advances in the development and modification of platelet-derived biomaterials and discuss their future use by focusing on a standardized preparation of these plateletderived biomaterials.

Historical background

Advances in platelet-derived biomaterials for regenerative medicine are illustrated in chronological order in Fig. 1. As a biomaterial, PRP was first applied as a ‘‘glue’’ in surgical & Tomoyuki Kawase 1 Division of Oral Bioengineering, Institute of Medicine and

Dentistry, Niigata University, Niigata 951-8514, Japan 2 Advanced Research Center, The Nippon Dental University

School of Life Dentistry at Niigata, Niigata 951-8580, Japan 123


DOI 10.1007/s10266-015-0209-2 operations in the 1970s and is essentially identical to the present-day fibrin glue [9]. Currently, fibrin glue is generally prepared from platelet-poor plasma (PPP) [10]; several different protocols for this preparation now exist; therefore, the end products have been characterized and are distinct from one another. Based on results from earlier reports [9] and its application in surgical fields, fibrin glue is generally considered to have a positive effect on tissue repair and regeneration [11, 12].

From the earliest reports on the efficacy of fibrin glue, almost 30 years elapsed since PRP was identified as a promising reservoir of growth factors, and subsequently, began to be applied in regenerative medicine. Breakthrough studies in the late 1990s and early 2000s found that

PRP facilitated skeletal regeneration [13–15]. Based on the theory that multiple growth factors involved in tissue regeneration are highly concentrated in PRP, Marx et al. tested the feasibility of using PRP in alveolar ridge augmentation and proposed PRP to be effective in the field of oral and maxillofacial surgery [16].

Due to the inherent liquid-form of PRP, preparations are converted to a gel-form prior to clinical use. This conversion was achieved by adding bovine thrombin to PRP preparations to minimize the rapid diffusion of growth factors at the site of application. This procedure continues to be a conventional method for clotting as reported in several review articles [17– 19]. In 2006, Choukroun and co-workers developed a novel technique for the purpose of eliminating xenofactors [20].

Using this technique, liquid PRP clotting was achieved by stimulating only the endogenous coagulation pathway. As a result, this technique has simplified the PRP preparation

Table 1 Major growth factors and cytokines contained in platelet-rich plasma

Category Factor Biological function

Growth factors PDGF Stimulate cellular growth, proliferation, healing, and cellular differentiation through regulation of a variety of cellular processesTGF-b




Angiogenic factors VEGF Exert a fundamental role in the process of blood vessel formation

Pro-inflammatory cytokines

IL-1 Promote systemic inflammation



Other factors Serotonin Influence the biological aspects of wound healing





PDGF platelet-derived growth factor, TGF-b transforming growth factor-b, IGF-I insulin-like growth factor-I, VEGF vascular endothelial growth factor, EGF epithelial growth factor, IL-1 interleukin-1, IL-6 interleukin-6, TNF-a tumor necrosis factor-a