Enhanced Osteogenic Differentiation of Human Mesenchymal Stem Cells with Synthetic Coral Matrix in the Presence or Absence of Growth Factors from the Platelet Rich-rich Plasma

Abstract

To solve problems in using natural sea corals with high biocompatibility, good osteoconductivity, and ideal degradability, a synthetic three-dimensional coral matrix was fabricated and observed for its capability to enhance osteogenic differentiation of human mesenchymal stem cells (h-MSCs), in the presence or absence of growth factors (GFs) supplied from platelet-rich plasma (PRP). Expressions of runx, osterix, and osteocalcin were investigated, following cell attachment, and proliferation analysis. Ectopic bone formation in nonosseous tissues of Sprague-Dawley rats at predetermined time intervals was investigated, including mineralized tissue growth in vivo. The 3D synthetic coral matrix (SCM) can interact with the GF cocktail in the PRP and MSCs to generate and secret bone extracellular matrix (ECM) both in vitro and in vivo. The matrix supplied with GF cocktail from the PRP provided an ideal microenvironment for MSCs to attach, proliferate, and differentiate into osteoblast faster, as indicated by the expression levels of runx2, osterix, and osteocalcin. The high capability of SCMs to enhance bone formation has been proven by the formation of ectopic bones in the nonosseous environment. The incorporated PRP provided blood proteins such as fibrin to slow down matrix degradation, whereas GF supplied by the PRP stimulated h-MSCs to attach and proliferate onto the matrix. Moreover, the GF supplied by the PRP enhanced osteogenic differentiation and mineralization, accelerating bone regeneration. Valorization phases are needed to apply the SCM for bone tissue engineering in clinics. HIGHLIGHTS A synthetic coral matrix (SCM) with ideal macro- and microstructural appearance and physical and chemical properties, with tunable platelet-rich plasma (PRP)-loading capacity and release manner, was successfully fabricated The matrix provided an ideal microenvironment for human mesenchymal stem cells (h-MSCs) to attach, proliferate, and differentiate into osteoblasts indicated by high expression levels of bone regeneration markers The high capability of SCM to enhance bone regeneration has been validated by the formation of ectopic bones in the nonosseous environment of subcutaneous rat dorsal tissues The incorporation of a growth factor cocktail from the PRP did not alter the results in the matrix without growth factors, which act as signaling molecules The SCM was found to degrade faster in the group without h-MSCs, indicating that the system with cells promoted faster bone formation GRAPHICAL ABSTRACT