Bioinspired materials for regenerative medicine and drug delivery applications

Abstract

The structural organization and functional capabilities of natural materials have inspired many technological and scientific developments. Biological systems are under constant pressure for innovation due to the constraints imposed by natural selection, which has allowed various organisms to surmount engineering challenges in ways that can scarcely be matched by modern science. Biomimetics or bioinspiration is a field that focuses on the adaptation of engineering principles observed in biological models to fabricate materials capable of circumventing longstanding problems in fields such as energy and medicine. This transition from biological systems has facilitated the design of effective materials, structures or processes within the range of nature’s adaptations and strategies. In the first study of this thesis, I describe the development of a bioactive scaffold composed of adamantyl-conjugated, laminin-derived bioactive IKVAV peptide molecules enmeshed in electrospun cyclodextrin nanofiber (CDNFs). Accordingly, host-guest interactions between adamantyl groups on peptide termini and cyclodextrin molecules on electrospun nanofiber surfaces were utilized to produce a composite material for the treatment of neurodegenerative disorders. Electrospun CDNFs provided a 3-dimensional environment conductive for the growth of PC12 cells and expressed functionalized bioactive epitopes on their surfaces to enhance the differentiation of neural progenitors. In addition, CDNFs further supported neural growth through their highly aligned mesh structure. Neural bIII tubulin and synaptophysin I gene expression levels significantly increased when PC12 cells were cultured on aligned and IKVAV-functionalized CDNFs. Neurite extension of PC12 cells also increased significantly when cultured on aligned and IKVAVfunctionalized CDNFs when compared to random and unfunctionalized electrospun CDNFs. As such, these nanofibers are able to effectively induce the neural differentiation of PC-12 cells through the physical and biochemical signals provided by their structure and bioactive sequence. The second part of the present thesis focuses on the local delivery of gemcitabine, a cytotoxic cancer drug that is rapidly degraded in plasma and cannot be encapsulated in conventional delivery vesicles due to its highly hydrophobic nature. In order to overcome these limitations, gemcitabine was coupled with Fmoc-Gly and integrated into a peptide-based nanocarier system in order to control drug concentration within the therapeutic range and minimize the adverse effects. Two oppositely-charged amyloid inspired peptides (Fmoc-AIPs) were chosen as drug carrier systems. These molecules self assemble into nanofiber structures at physiological conditions through non-covalent interactions. Overall, the present thesis demonstrates the significance of peptide-based materials for the purpose of designing functional bioinspired/biomimetic materials for various cellular applications such as tissue engineering and drug delivery. The complexity of nature necessitates the design of biomaterials that can mimic the cellular microenvironment for the treatment of diseases, and further insight into natural processes will no doubt enhance our ability to overcome the engineering challenges presented by modern medicine.