Abstract
Electrical stimulus-responsive drug delivery from conducting polymers such as polypyrrole (PPy) has been limited by lack of versatile polymerization techniques and limitations in drug-loading strategies. In the present study, we report an in-situ chemical polymerization technique for incorporation of biotin, as the doping agent, to establish electrosensitive drug release from PPy-coated substrates. Aligned electrospun polyvinylidene fluoride (PVDF) fibers were used as a substrate for the PPy-coating and basic fibroblast growth factor and nerve growth factor were the model growth factors demonstrated for potential applications in musculoskeletal tissue regeneration. It was observed that 18-h of continuous polymerization produced an optimal coating of PPy on the surface of the PVDF electrospun fibers with significantly increased hydrophilicity and no substantial changes observed in fiber orientation or individual fiber thickness. This PPy-PVDF system was used as the platform for loading the aforementioned growth factors, using streptavidin as the drug-complex carrier. The release profile of incorporated biotinylated growth factors exhibited electrosensitive release behavior while the PPy-PVDF complex proved stable for a period of 14 days and suitable as a stimulus responsive drug delivery depot. Critically, the growth factors retained bioactivity after release. In conclusion, the present study established a systematic methodology to prepare PPy coated systems with electrosensitive drug release capabilities which can potentially be used to encourage targeted tissue regeneration and other biomedical applications.
Highlights
Bioelectrical stimuli have been extensively harnessed to stimulate cellular activity and promote tissue regenerative response within several tissue types including bone (Porter et al, 2009), nerve (Ghasemi-Mobarakeh et al, 2011), skeletal muscle (Donnelly et al, 2010) and cardiac muscle (Radisic et al, 2004)
Polyvinylidene fluoride (PVDF) electrospun fibers were used as a model substrate for deposition of polypyrrole (PPy) coating in which biotin was incorporated via chemical polymerization
Scanning Tunneling Electron Microscopy (STEM) demonstrated that PPy polymerization resulted in PPy fibers and debris deposited haphazardly around the PVDF fibers in the initial hours of polymerization until it formed a uniform coating around the PVDF fibers with minimal randomly oriented debris after 18 h of polymerization (Figure 2)
Summary
Bioelectrical stimuli have been extensively harnessed to stimulate cellular activity and promote tissue regenerative response within several tissue types including bone (Porter et al, 2009), nerve (Ghasemi-Mobarakeh et al, 2011), skeletal muscle (Donnelly et al, 2010) and cardiac muscle (Radisic et al, 2004). Poly-pyrrole (PPy), a bio-compatible polymer is an ideal candidate to elicit such responses because of its inherent electrical conductivity and ability to be used as a biomaterial scaffold substrate. These attributes of PPy have been widely demonstrated to stimulate regeneration of multiple tissues including bone (Sajesh et al, 2013; Song et al, 2016), nerve (Stewart et al, 2015; Thunberg et al, 2015), skeletal muscle (Gilmore et al, 2009; Browe and Freeman, 2019), and cardiac muscle (Kai et al, 2011; Spearman et al, 2015). In order to circumvent these limitations, biotin has been previously investigated as a dopant to be conjugated to form a drug complex for further drug release in electro-deposited PPy (George et al, 2006)
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