Abstract
Stimuli-responsive materials are very attractive candidates for on-demand drug delivery applications. Precise control over therapeutic agents in a local area is particularly enticing to regulate the biological repair process and promote tissue regeneration. Macromolecular therapeutics are difficult to embed for delivery, and achieving controlled release over long-term periods, which is required for tissue repair and regeneration, is challenging. Biohybrid composites incorporating natural biopolymers and electroconductive/active moieties are emerging as functional materials to be used as coatings, implants or scaffolds in regenerative medicine. Here, we report the development of electroresponsive biohybrid composites based on Bombyx mori silkworm fibroin and reduced graphene oxide that are electrostatically loaded with a high-molecular-weight therapeutic (i.e., 26 kDa nerve growth factor-β (NGF-β)). NGF-β-loaded composite films were shown to control the release of the drug over a 10-day period in a pulsatile fashion upon the on/off application of an electrical stimulus. The results shown here pave the way for personalized and biologically responsive scaffolds, coatings and implantable devices to be used in neural tissue engineering applications, and could be translated to other electrically sensitive tissues as well.
Highlights
Drug delivery technologies are a multibillion-dollar global industry [1]
With a view to treat nerve injuries and develop a combinatorial tissue engineered approach, we report here the development of electroresponsive biohybrid composites based on Bombyx mori silk fibroin (SF), which acts as the continuous phase, and reduced graphene oxide as a conductive dispersed phase
B. mori silk fibroin-based materials absorb water, we observed no major differences in the swelling ratio of the films with the inclusion of reduced graphene oxide (rGO) (Figure 1b), with a swelling ratio of ~25% for all films, regardless of rGO content
Summary
Driving the increase in research and development efforts [2] is the market need for devices and ‘smart’ implants or scaffolds capable of delivering active agents at specific rates. These systems can be controlled by either physical (e.g., electromagnetic fields, electrical stimulation, temperature) or (bio)chemical (e.g., enzymes, ions, pH) stimuli, in single or combined mechanisms. These technologies enable greater control over the delivery of drugs compared to traditional systems that rely on passive delivery, which cannot be modified in response to therapeutic demand [3]. Combining a protein found in nature as the matrix phase with a conductive component to provide additional functionality offers a multifunctional platform for developing coatings, implants or scaffolds for tissue engineering to match a variety of tissues in surgical reconstruction and regeneration [14]
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