Abstract
This work introduces casein microstructures with surface features as a biodegradable biomedical platform technology for enhancing tissue-engineering applications. An optimized fabrication process is presented to reduce the hydrophobicity of intermediate polydimethylsiloxane (PDMS) molds and to transfer high-resolution regular and biomimetic features onto the surface of casein devices. Four different cross-linking reagents, glutaraldehyde, formaldehyde, citric acid and transglutaminase (TG) were investigated to increase the degradation time of casein and their influence on swelling and biocompatibility of the films was studied. TG was found to be the only cross-linker to effectively increase the degradation time and show reduced film swelling after immersion into media, while remaining compatible with cell-culture. The maximum expansion of the films cross-linked via TG was 33% after 24 hours of immersion in cell-culture media. C2C12 cells were successfully cultured on the patterned films for up to 72 hours. The patterned biodegradable casein substrates presented here have promising applications in stem-cell engineering, regenerative medicine, and implantable devices.
Highlights
INTRODUCTIONBiological cells cultured on engineered surfaces, with either regular[1,2,3,4] or bioimprinted cellular[5,6,7,8,9,10] micro- and nano-scale features, have shown a distinctive behaviour regarding their proliferation, regulation and response to drugs, as compared to when cultured on flat surfaces
Surface topography is one the parameters which is known to influence cell phenotype
We report cross-linking of casein films using four different cross-linking reagents and we demonstrate the change in the size of films and resolution-improved features on the films for each cross-linker
Summary
Biological cells cultured on engineered surfaces, with either regular[1,2,3,4] or bioimprinted cellular[5,6,7,8,9,10] micro- and nano-scale features, have shown a distinctive behaviour regarding their proliferation, regulation and response to drugs, as compared to when cultured on flat surfaces Such patterns have typically been replicated onto non-biodegradable, but cell-compatible materials such as Polystyrene and polydimethylsiloxane (PDMS), which are commonly used for engineering purposes, as well as some metals used in implants. For the first time, the successful use of patterned cross-linked casein films as cell-culture substrates
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