3D Micro and Nano Fabrication Techniques for Designing Biologically Inspired, Anisotropic Tissue Constructs for Bone, Cartilage and Osteochondral Tissue Regeneration Open Access
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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 that has thus far proven to be very promising is tissue engineering [1, 2]. Since cartilage matrix is nanocomposite, the goal of the current work is to use nanomaterials and nano/microfabrication 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 were fabricated in this study. In vitro hMSC studies showed that stem cells prefer to attach in the scaffolds with smaller fiber diameter. More importantly, our in vitro differentiation results demonstrated that incorporation of the biomimetic carbon nanotubes and poly L-lysine coating can induce more chondrogenic differentiations of MSCs than controls, which make them promising for cartilage tissue engineering applications. These results were then used to inspire the design and fabrication of 3D printed polymer constructs, which were designed to mimic the osteochondral region of articulate joint, and to have enhanced mechanical characteristics when compared to traditional bi-phasic designs. Fabricated scaffolds were also subject to surface modification, both with a chemically functionalized acetylated collagen coating and through absorption via poly-L-lysine coated carbon nanotubes. In vitro proliferation results demonstrated not only that incorporation of the biomimetic carbon nanotubes and poly L-lysine coating and acetylated collagen can induce more proliferation of MSCs than controls, but that more controlled and biomimetically designed features also enhance proliferation of MSCs.