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TitleAssociation of platelet-rich plasma and auto-crosslinked hyaluronic acid microparticles: approach for orthopedic application
Author(s)Shimojo, Andréa Arruda Martins
Duarte, Adriana da Silva Santos
Duarte Lana, José Fábio Santos
Luzo, Ângela Cristina Malheiros
Fernandes, Ana Rita
Sanchez-Lopez, Elena
Souto, Eliana
Santana, Maria Helena Andrade
Keywordsplatelet-rich plasma
polyelectrolyte complexes
auto-crosslinked hyaluronic acid
cell proliferation
Issue date26-Sep-2019
CitationMartins Shimojo, Andréa Arruda; Santos Duarte, Adriana da Silva; Santos Duarte Lana, José Fábio; Malheiros Luzo, Ângela Cristina; Fernandes, Ana Rita; Sanchez-Lopez, Elena; Souto, Eliana; Andrade Santana, Maria Helena, Association of platelet-rich plasma and auto-crosslinked hyaluronic acid microparticles: approach for orthopedic application. Polymers, 11(10), 1568, 2019
Abstract(s)Platelet-rich plasma (PRP) associated with high molecular weight hyaluronic acid (HA) has been clinically used for tissue regeneration in orthopedics. Despite the recognized beneficial clinical outcomes (e.g., early pain control, improvement of patients functional limitation and longer-term effectiveness compared to PRP and HA alone in mild and moderate osteoarthritis treatments), its use is still challenging and controversial due to lack of standardization of association practical protocols. Moreover, most studies neglect the matrix structure, that generates the ultimate properties of the association among platelets, fibrin network and the microparticles. In the present work, we aimed to analyze the influence of the PRP/HA association with a controlled matrix structure on the stability, rheological behavior, release of growth factors and in vitro proliferation of human adipose-derived mesenchymal cells (h-AdMSCs). The attenuation of the negative charge of HA was also evaluated. Pure PRP (P-PRP) (i.e., plasma enriched with platelets and poor in leukocytes) was prepared by centrifugation and activated with serum and calcium chloride (AP-PRP). Autocrosslinked hyaluronic acid (AHA) was prepared by organocatalyzed auto-esterification and structured in microparticles (MPAHA) by shearing. The attenuation of the negative charge of MPAHA was performed with chitosan (CHT) by polyelectrolyte complexation yielding MPAHA-CHT. The results showed that microparticles (MPs) have viscoelastic properties, extrusion force and swelling ratio appropriate for injectable applications. The association of AP-PRP with the controlled structure of MPAHA and MPAHA-CHT formed a matrix composed of platelets and of a fibrin network with fibers around 160 nm located preferably on the surface of the MPs with an average diameter of 250 m. Moreover, AP-PRP/MPAHA and AP-PRP/MPAHA-CHT associations were non-toxic and supported controlled growth factor (PDGF-AB and TGF-1) release and in vitro proliferation of h-AdMSC with a similar pattern to that of AP-PRP alone. The best h-AdMSC proliferation was obtained with the AP-PRP/MPAHA-CHT75:25 indicating that the charge attenuation improved the cell proliferation. Thus, the association of AP-PRP with the controlled structure of HA can be a valuable approach for orthopedic applications.
Publisher version
AccessOpen access
Appears in Collections:CEB - Publicações em Revistas/Séries Internacionais / Publications in International Journals/Series

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