Figure 1.

An autologous liquid-to-gel dynamic scaffold as a carrier of biological mediators in tissue repair. When liquid plasma rich in growth factors (GFs) is applied directly into tissue, the newly formed three-dimensional matrix clot traps many of the released growth factors and cytokines from platelet degranulation and from plasma by binding them to the heparin sulfate proteoglycan domains of fibrin matrix components in a non-diffusible mode (yuxtacrine or matricrine) (A). However, some GFs in a diffusion mode (autocrine and paracrine) will directly reach their cognate cell-surface receptor (D), thereby inducing an immediate cell-biosynthetic and cell-behavior modification (C). The ensuing progressive biodegradation of a fibrin clot is mediated by the serine protease plasmin, which is yielded through both the activation of plasminogen by a tissue plasminogen activator [24] and the immune and mesenchymal cells that migrate into the clot, thereby matching the speed of the ingrowing repair tissue [17,21,22,25,26] (B). GFs act as extracellular ligands by binding to transmembrane receptors arrayed on the surface of target cells, thereby activating intracellular signal transduction pathways that convey the signal to the nucleus to eventually induce a wide range of cell specifications during inflammation and the repair process including cell survival, proliferation, migration, differentiation, and maturation and changes in protein synthesis and metabolism (C). These effects include the synthesis and secretion of GFs and cytokines, which interact with their receptors in a diffusible manner (autocrine and paracrine pathways); the synthesis of extracellular matrix (ECM) components such as collagens, decorin, hyaluronic acid, and glycosaminoglycans; and cell survival, proliferation, differentiation, and migration (C) [17]. Only by understanding the unbreakable link between GFs and fibrin matrix will we grasp the in situ biological function of PRP and the additional pivotal fact that it is not necessary to combine this product with other delivery systems to slowdown the release of GFs.