Novel Biologically Inspired Nanostructured Scaffolds for Directing Chondrogenic Differentiation of Mesenchymal Stem Cell
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Novel Biologically Inspired Nanostructured Scaffolds for Directing Chondrogenic Differentiation of Mesenchymal Stem Cells Benjamin Holmes1; Nathan J. Castro1; Jian Li1 and Lijie Grace Zhang1,2 1
Department of Mechanical and Aerospace Engineering and 2Department of Medicine, The George Washington University, Washington, DC 20052.
ABSTRACT Cartilage defects, which are caused by a variety of reasons such as traumatic injuries, osteoarthritis, or osteoporosis, represent common and severe clinical problems. Each year, over 6 million people visit hospitals in the U.S. for various knee, wrist, and ankle problems. As modern medicine advances, new and novel methodologies have been explored and developed in order to solve and improve current medical problems. One of the areas of investigation is tissue engineering [1, 2]. Since cartilage matrix is nanocomposite, the goal of the current work is to use nanomaterials and nanofabrication methods to create novel biologically inspired tissue engineered cartilage scaffolds for facilitating human bone marrow mesenchymal stem cell (MSC) chondrogenesis. For this purpose, through electrospinning techniques, we designed a series of novel 3D biomimetic nanostructured scaffolds based on carbon nanotubes and biocompatible poly(L-lactic acid) (PLLA) polymers. Specifically, a series of electrospun fibrous PLLA scaffolds with controlled fiber dimension and surface nanoporosity were fabricated in this study. In vitro hMSC studies showed that stem cells prefer to attach in the scaffolds with smaller fiber diameter or suitable nanoporous structures. More importantly, our in vitro differentiation results demonstrated that incorporation of the biomimetic carbon nanotubes and poly L-lysine coating can induce GAG and collagen synthesis that is indicative of chondrogenic differentiations of MSCs. Our novel scaffolds also performed better than controls, which make them promising for cartilage tissue engineering applications. INTRODUCTION As modern medicine advances, new and novel methodologies have been explored and developed in order to solve and improve current medical problems. One of the areas of investigation that has great promise is tissue engineering [1-3]. For many years, creating polymer scaffolds as a foundation for tissue growth has been widely investigated [4]. A very common and well established method for creating these scaffolds is a process called electrospinning. Electrospinning has been considered favorable because of the ability of researchers to create polymer scaffolds on the micro and nanoscale that mimic the extracellular matrix (ECM) and create an environment which improves cell proliferation and differentiation [5]. And while the system parameters have been thoroughly investigated, research is also being done into how polymer scaffolds can be further modified to increase their physical and compositional complexities, as well as have a greater impact on cell growth. Electrospinning is also favorable because of the ease of scaffold fabrication, the ability to incorporate nano a
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