Effects of a Bioactive SPPEPS Peptide on Chondrogenic Differentiation of Mesenchymal Stem Cells
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Annals of Biomedical Engineering ( 2019) https://doi.org/10.1007/s10439-019-02306-0
Effects of a Bioactive SPPEPS Peptide on Chondrogenic Differentiation of Mesenchymal Stem Cells SALMA MAHZOON,1 JAKOB M. TOWNSEND,2 THI N. LAM,3 VIRGINIE SJOELUND,4 and MICHAEL S. DETAMORE 2 1
School of Aerospace and Mechanical Engineering, University of Oklahoma, Norman, OK, USA; 2Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, OK, USA; 3Department of Microbiology and Plant Biology, University of Oklahoma, Norman, OK, USA; and 4Department of Cell Biology, University of Oklahoma Health Science Center, Oklahoma City, OK, USA (Received 17 August 2018; accepted 8 June 2019) Associate Editor Stefan M Duma oversaw the review of this article.
Abstract—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-b3) 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. Keywords—Chondroinductive peptide, Biomaterial, Hydrogel, Proteomics.
Address correspondence to Michael S. Detamore, Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, OK, USA. Electronic mail: [email protected]
INTRODUCTION Cartilage tissue does not have the ability to regenerate on its own. Minor injury to cartilage tissue may therefore lead to further degeneration and eventually to arthritis, which is the leading cause of disability worldwide. The current surgical treatments for cartilage injury such as autologous chondrocyte implantation (ACI), microfracture, osteochondral transplantation (mosaicplasty), and allograft implants, do not reproducibly lead to tissue with mechanical and structural properties comparable to native articular cartilage.19 The failure of current treatments to reproducibly regenerate a fully integrated and healthy cartilage tissue has motivated the regenerative medicine community to investigate strategies that lead to t
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