Engineering and Information Technology Collected Works - Research Publications
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ItemDynamic and Responsive Growth Factor Delivery from Electrospun and Hydrogel Tissue Engineering Materials(WILEY, 2018-01-10)Tissue engineering scaffolds are designed to mimic physical, chemical, and biological features of the extracellular matrix, thereby providing a constant support that is crucial to improved regenerative medicine outcomes. Beyond mechanical and structural support, the next generation of these materials must also consider the more dynamic presentation and delivery of drugs or growth factors to guide new and regenerating tissue development. These two aspects are explored expansively separately, but they must interact synergistically to achieve optimal regeneration. This review explores common tissue engineering materials types, electrospun polymers and hydrogels, and strategies used for incorporating drug delivery systems into these scaffolds.
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ItemScaffolds Formed via the Non-Equilibrium Supramolecular Assembly of the Synergistic ECM Peptides RGD and PHSRN Demonstrate Improved Cell Attachment in 3D(MDPI, 2018-07)Self-assembling peptides (SAPs) are a relatively new class of low molecular weight gelators which immobilize their solvent through the spontaneous formation of (fibrillar) nanoarchitectures. As peptides are derived from proteins, these hydrogels are ideal for use as biocompatible scaffolds for regenerative medicine. Importantly, due to the propensity of peptide sequences to act as signals in nature, they are easily functionalized to be cell instructive via the inclusion of bioactive epitopes. In nature, the fibronectin peptide sequence, arginine-glycine-aspartic acid (RGD) synergistically promotes the integrin α₅β₁ mediated cell adhesion with another epitope, proline-histidine-serine-arginine-asparagine (PHSRN); however most functionalization strategies focus on RGD alone. Here, for the first time, we discuss the biomimetic inclusion of both these sequences within a self-assembled minimalistic peptide hydrogel. Here, based on our work with Fmoc-FRGDF (N-flourenylmethyloxycarbonyl phenylalanine-arginine-glycine-aspartic acid-phenylalanine), we show it is possible to present two epitopes simultaneously via the assembly of the epitopes by the coassembly of two SAPs, and compare this to the effectiveness of the signals in a single peptide; Fmoc-FRGDF: Fmoc-PHSRN (N-flourenylmethyloxycarbonyl-proline-histidine-serine-arginine-asparagine) and Fmoc-FRGDFPHSRN (N-flourenylmethyloxycarbonyl-phenylalanine-arginine-glycine-asparticacid-phenylalanine-proline-histidine-serine-arginine-asparagine). We show both produced self-supporting hydrogel underpinned by entangled nanofibrils, however, the stiffness of coassembled hydrogel was over two orders of magnitude higher than either Fmoc-FRGDF or Fmoc-FRGDFPHSRN alone. In-vitro three-dimensional cell culture of human mammary fibroblasts on the hydrogel mixed peptide showed dramatically improved adhesion, spreading and proliferation over Fmoc-FRGDF. However, the long peptide did not provide effective cell attachment. The results demonstrated the selective synergy effect of PHSRN with RGD is an effective way to augment the robustness and functionality of self-assembled bioscaffolds.
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ItemA Programmed Anti-Inflammatory Nanoscaffold (PAIN) as a 3D Tool to Understand the Brain Injury Response(WILEY-V C H VERLAG GMBH, 2018-12-13)Immunology is the next frontier of nano/biomaterial science research, with the immune system determining the degree of tissue repair. However, the complexity of the inflammatory response represents a significant challenge that is essential to understand for the development of future therapies. Cell-instructive 3D culture environments are critical to improve our understanding of the link between the behavior and morphology of inflammatory cells and to remodel their response to injury. This study has taken two recent high-profile innovations-functional peptide-based hydrogels, and the inclusion of anti-inflammatory agents via coassembly-to make a programmed anti-inflammatory nanoscaffold (PAIN) with unusual and valuable properties that allows tissue-independent switching of the inflammatory cascade. Here, extraordinary durability of the anti-inflammatory agent allows, for the first time, the development of a 3D culture system that maintains the growth and cytoskeletal reorganization of brain tissue, while also facilitating the trophic behavior of brain cells for 22 d in vitro. Notably, this behavior was confirmed within an active scar site due to the unprecedented resilience to the presence of inflammatory cells and enzymes in the brain. Efficacy of the culture system is demonstrated via novel insights about inflammatory cell behavior, which would be impossible to obtain via in vivo experimentation.