Carbon nanotubes as electrophysiological building blocks for a bioactive cell scaffold through biological assembly to induce osteogenesis

Bio-functional cell scaffolds have great potential in the field of tissue regenerative medicine. In this work, a carbon nanotube (CNT) gel scaffold <i>via</i> specific pairing of functionalized nucleobases was developed for specifically targeted drug delivery and <i>in vitro</i> osteogenesis. The CNT gel scaffold with nano-fibrous architectures was established by Watson-Crick base pairing between thymine and adenine of low molecular weight heparin, respectively. As scaffold precursors, adenine and thymine functionalized heparin derivatives could additionally bind cell growth factors by the affinity interaction. The resulting nano-fibrous gel scaffolds showed excellent mechanical integrity and advanced electro-physiological functions. Potential application of the electrophysiological CNT gel scaffold in bone tissue engineering was confirmed by encapsulation of human adipose-derived stem cells (ASCs). Our results indicate that the electrically conductive networks formed by CNTs within the nano-fibrous framework are the key characteristics of cell scaffolds leading to improved ASC organization and differentiation by an extra electrical stimulus (ES). Specifically, ASCs cultured in bio-electrical gel scaffolds showed ∼4 times higher spontaneous osteogenesis in combination with bone morphogenetic protein 2 (BMP-2), compared to those cultured on pristine hydrogels. This electrophysiological CNT gel scaffold containing BMP-2 exhibited beneficial effects on ASC activity and osteogenetic differentiation, which suggested a promising future for local treatment of bone regeneration.