In vitro differentiation and biocompatibility of mesenchymal stem cells on a novel platelet releasate-containing injectable composite.

Abstract

Underlying changes in subchondral and cancellous bone precede joint degeneration in spinal discs, knees, hips, and other joints. We hypothesize that an early bone remodeling intervention therapy may alleviate or postpone the later manifestation of joint failure. Utilization of a novel biomaterial for injection deliverability to the underlying subchondral and cancellous bone during the onset of osseous changes, before severe cartilaginous damage, is proposed. In this preliminary study, we introduced novel platelet releasate-containing alginate/calcium phosphate composites for this intervention therapy and evaluated them in vitro through mesenchymal stem cell biocompatibility and induction of osteochondral differentiation. DNA quantification and gene expression profiles suggested mesenchymal stem cells were directed along an osteochondral differentiation pathway, more specifically, to the immature nonhypertrophic chondrocyte phenotype. These conclusions were based on reduced mitogenic activity, a rapid upregulation followed by suppression of Runx2 transcription factor mRNA, sustained upregulation of Sox9 transcription factor mRNA and the absence of late marker expressions for both mature articular chondrocytes and osteoblasts over the course of 14 days. Initial findings in regard to the use of these materials for bone remodeling were positive and support the execution of future studies evaluating the inflammatory and angiogenic aspects of the materials. In this study, we have considered one of the many aspects of the endochondral ossification process; neovascularization and resorption of bone with an irregular physiology need to be evaluated.