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Processing novel electrospun polymer scaffolds for biomedical applications
[Thesis]. Manchester, UK: The University of Manchester; 2014.
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Abstract
Electrospinning has proven to be a viable method of producing nano to micro scale fibresfrom a variety of materials. These fibres typically form non-woven mats displayingsignificantly large surface to volume ratios and networks of interconnected pores. Increasinginterest in the utilisation of these fibre mats for medical research has been a trend over the lastdecade, but, despite significant progress, major technological hurdles still exist to routineproduction and utilization. Potential applications for electrospun fibres in medicine includetissue engineering and regenerative medicine, drug delivery and semi-permeable wounddressings. The aims of this study were to investigate the process parameters governingelectrospun fibre morphology and then apply this to the fabrication of novel biomaterialscaffolds capable of eliciting applicable and reproducible biological responses. A highlyconfigurable electrospinning rig was assembled with the capability of consistently producingspecific fibre morphologies, whilst at the same time recording the process parameters via anelectronic computer interface. Temperature and humidity control facilitated the establishmentof controlled environments for a variety of electrospinning experiments. Scaffolds producedwere rigorously characterised using techniques such as scanning electron and confocalmicroscopy and surface tension (water contact angle) analysis. The biocompatibility ofscaffold design was assessed using in vitro cell culture experiments that included analyticalassays and imaging. An empirical model for predicting changes to electrospun poly–ε-caprolactone (PCL) fibre diameter based on induced changes to the electrospinning processwas developed. The accuracy of the model was tested by predicting the mean fibre diametersproduced under several conditions on our industrial partner‘s multi-nozzle electrospinning rig.Subsequent testing of these conditions on the multi-nozzle apparatus showed a correlationregression of 0.956 between predicted values and experimentally measured results. Alignedfibres electrospun from PCL-chitosan blends were produced for a range of volume ratioblends of the two materials. The blended fibre scaffolds showed improved mechanicalproperties over pure chitosan scaffolds. Investigation into the inflammatory cytokineexpression of murine macrophage cells in the presence of blended fibres was undertaken.Scaffolds containing at least 25% chitosan by weight were found to significantly reduceperoxide and cytokine expression from macrophage cells in comparison to controls. PCLsolutions were also functionalised with surfactant additives and electrospun into non-wovenmats. The influence of surfactant in solution elicited a small change in fibre diametersproduced, as well as significant differences in the wettability of the spun scaffolds. Theincorporation of lecithin, mannitol and sodium lauryl sulphate into PCL was tested accordingto ISO 10993-5 for cytotoxicological effects – results demonstrated that all scaffoldcompositions had retained their biocompatibility. Imaging of cells cultured on functionalisedPCL scaffolds showed significantly improved cell infiltration into the porous networkcompared to untreated PCL fibres. Poor cell infiltration has been recognised as a majorobstacle to widespread adoption of electrospun scaffolds and this novel functionalisationmethod shows great potential for further study. The contributions presented in this thesisreveal improved protocols for controlling and monitoring the production of predictableelectrospun fibre morphologies. These techniques were employed to produce electrospunscaffolds with properties targeted to specific cell interactions. Results show that control overscaffold morphology and the inclusion of bioactive agents can significantly improve thesuitability of these materials.