Association of Platelet-Rich Plasma and Auto-Crosslinked Hyaluronic Acid Microparticles: Approach for Orthopedic Application

Abstract

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 μm. Moreover, AP-PRP/MPAHA and AP-PRP/MPAHA-CHT associations were non-toxic and supported controlled growth factor (PDGF-AB and TGF-β1) 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.

Combined Platelet-Rich Plasma and Hyaluronic Acid can Reduce Pain in Patients Undergoing Arthrocentesis for Temporomandibular Joint Osteoarthritis

“…Similar studies in the orthopedic field also corroborate the findings of our study (the advantage of PRP+HA injection). 10,26,32 Studies concerning osteoarthritis of the knee have also recognized that simultaneous PRP and HA injections are safe and beneficial methods. Combining these 2 medications has been advocated for obtaining highly satisfactory clinical outcomes.…”

“…Combining these 2 medications has been advocated for obtaining highly satisfactory clinical outcomes. 10,26,32 Satuverithan et al also employed intrajoint HA+PRP injection for treating knee OA. This method was proven to be highly effective for pain alleviation and functional improvement until 6 months post-treatment.…”

“…Martins Shimojo et al also consider intraarticular PRP+HA injection to be a useful, effective, and safe clinical approach for treating osteoarthritic joints, which is in accordance with the findings of the present study. 32…”

The Potential Role of Polyelectrolyte Complex Nanoparticles Based on Cashew Gum, Tripolyphosphate and Chitosan for the Loading of Insulin

“…Such interest is attributed to their degradability, biocompatibility and non-toxic profile. Besides this, when combined with other polymers, a range of structures, such as gels, layer-by-layer films, excipients and/or even nanometric scale drug delivery systems, can be obtained with improved properties when compared to synthetic polymers [2][3][4][5].…”

“…However, due to the physicochemical features of the molecule and biopharmaceutical characteristics, the subcutaneous route still constitutes the main form of treatment [22]. A possible alternative to overcome the limitations of this drug is the use of polyelectrolytic complexes [1,4]. Therefore, the present study aims to produce polyelectrolytic complexes through the interaction between GC and CH, intermediated by the use of the reticulating agent sodium tripolyphosphate (TPP).…”