Bio-functional cell scaffolds have great potential in the field of tissue regenerative medicine. In this work, a carbon nanotube (CNT) gel scaffold via specific pairing of functionalized nucleobases was developed for specifically targeted drug delivery and in vitro 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.
For practical adipose regeneration, the challenge is to dynamically deliver the key adipogenic insulin-like growth factors in hydrogels to induce adipogenesis. In order to achieve dynamic release, smart hydrogels to sense the change in the blood glucose concentration is required when glucose concentration increases. In this study, a heparin-based hydrogel has been developed for use in dynamic delivery of heparin nanospheres containing insulin-like growth factor. The gel scaffold was facilely prepared in physiological conditions by the formation of boronate-maltose ester cross-links between boronate and maltose groups of heparin derivatives. Due to its intrinsic glucose-sensitivity, the exposure of gel scaffold to glucose induces maltose functionalized nanospheres dissociation off hydrogel network and thereby could dynamically move into the microenvironment. The potential of the hydrogel as a cell scaffold was demonstrated by encapsulation of human adipose-derived stem cells (ASCs) within the gel matrix in vitro. Cell culture showed that this dynamic hydrogel could support survival and proliferation of ASCs. This biocompatible coupling chemistry has the advantage that it introduces no potentially cytotoxic groups into injectable gel scaffolds formed and can create a more biomimetic microenvironment for drug and cell delivery, rendering them more suitable for potential in vivo biomedical applications. All these results indicate that this biocompatible gel scaffold can render the formulation of a therapeutically effective platform for diabetes treatment and adipose regeneration.
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