Effects of a Bioactive SPPEPS Peptide on Chondrogenic Differentiation of Mesenchymal Stem Cells

A synthetic 'chondroinductive' biomaterial that could induce chondrogenesis without the need for growth factors, extracellular matrix, or pre-seeded cells could revolutionize orthopedic regenerative medicine. The objective of the current study was thus to introduce a synthetic SPPEPS peptide and evaluate its ability to induce chondrogenic differentiation. In the current study, dissolving a synthetic chondroinductive peptide candidate (100 ng/mL SPPEPS) in the culture medium of rat bone marrow-derived mesenchymal stem cells (rBMSCs) elevated collagen type II gene expression compared to the negative control (no growth factor or peptide in the cell culture medium) after 3 days. In addition, proteomic analyses indicated similarities in pathways and protein profiles between the positive control (10 ng/mL TGF-β₃) and peptide group (100 ng/mL SPPEPS), affirming the potential of the peptide for chondroinductivity. Incorporating the SPPEPS peptide in combination with the RGD peptide in pentenoate-functionalized hyaluronic acid (PHA) hydrogels elevated the collagen type II gene expression of the rBMSCs cultured on top of the hydrogels compared to using either peptide alone. The evidence suggests that SPPEPS may be a chondroinductive peptide, which may be enhanced in combination with an adhesion peptide.