Our results indicate that nanocomposites, where carbon nanotubes have been added to hydrogel substrates, in combination with electrical stimulation provided improved conditions for neural growth and regeneration.
Owing to their exceptional physical, chemical, and mechanical properties, carbon nanotubes (CNTs) have been extensively studied for their effect on cellular behaviors. However, little is known about the process by which cells attach and spread on CNTs and the process for cell attachment and spreading on individual single-walled CNTs has not been studied. Cell adhesion and spreading is essential for cell communication and regulation and the mechanical interaction between cells and the underlying substrate can influence and control cell behavior and function. A limited number of studies have described different adhesion mechanisms, such as cellular process entanglements with multi-walled CNT aggregates or adhesion due to adsorption of serum proteins onto the nanotubes. Here, we hypothesized that cell attachment and spreading to both individual single-walled CNTs and multi-walled CNT aggregates is governed by the same mechanism. Specifically, we suggest that cell attachment and spreading on nanotubes is integrin-dependent and is facilitated by the adsorption of serum and cell-secreted adhesive proteins to the nanotubes.
Macroporous cell-laden
hydrogels have recently gained recognition
for a wide range of biomedical and bioengineering applications. There
are various approaches to create porosity in hydrogels, including
lyophilization or foam formation. However, many do not allow a precise
control over pore size or are not compatible with in situ cell encapsulation. Here, we developed novel templated macroporous
hydrogels by encapsulating uniform degradable hydrogel microspheres
produced via microfluidics into a hydrogel slab. The microspheres
degraded completely leaving macropores behind. Microsphere degradation
was dependent on the incubation medium, microsphere size, microsphere
confinement in the hydrogel as well as cell encapsulation. Uniquely,
the degradable microspheres were biocompatible and when laden with
cells, the cells were deposited in the macropores upon microsphere
degradation and formed multicellular aggregates. The hydrogel-encapsulated
cell aggregates were used in a small drug screen to demonstrate the
relevance of cell–matrix interactions for multicellular spheroid
drug responsiveness. Hydrogel-grown spheroid cultures are increasingly
important in applications such as in vitro tumor,
hepatocellular, and neurosphere cultures and drug screening; hence,
the templated cell aggregate-laden hydrogels described here would
find utility in various applications.
Carbon nanotube (CNT)-hydrogel nanocomposites are beneficial for various biomedical applications, such as nerve regeneration, tissue engineering, sensing, or implant coatings. Still, there are impediments to developing nanocomposites, including attaining a homogeneous CNT-polymer dispersion or patterning CNTs on hydrogels. While few approaches have been reported for patterning CNTs on polymeric substrates, these methods include high temperature, high vacuum or utilize a sacrificial layer and, hence, are incompatible with hydrogels as they lead to irreversible collapse in hydrogel structure. In this study, a novel two-step method is designed to transfer CNTs onto hydrogels. First, dense CNTs are grown on quartz substrates. Subsequently, hydrogel solutions are deposited on the quartz-grown CNTs. Upon gelation, the hydrogel with transferred CNTs is peeled from the quartz. Successful transfer is confirmed by scanning electron microscopy and indirectly by cell attachment. The efficient transfer is attributed to π-interactions pregelation between the polymers in solution and the CNTs.
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