3D self-folding tissue engineering scaffold origami

Q Science (General);T Technology (General)

Vasiev, Iskandar ; Nikolaj, Gadegaard

University:University of Glasgow

Department:School of Engineering

关键词: Nano, biomedical, tissue engineering, tissue scaffolds, regenerative medicine, microfabrication, nanotechnology, bioMEMS, smart materials, hydrogels, hESCs, stem cells;   

Others  :  http://theses.gla.ac.uk/7071/1/2015VasievPhD.pdf

来源: University of Glasgow

【 摘 要 】

In the field of tissue engineering complex 3D architecture has become increasingly relevant in the pursuit of precisely engineered control over living tissue. It is needed to recreate the heterogeneous and complex arrangements of cells seen in nature, and to be able to influence their proliferation, differentiation and fate. A method for the 3D structuring of cells is therefore desired and is something standard lithographic methods cannot provide - the precision engineered 3D cellular niche. This work transfers traditional 2D lithographic techniques used in MEMS (E-beam lithography, photolithography, soft lithography and nanoimprint lithography) to the construction of 3D as well as complex hierarchical structures compatible with cell culture. To address this, hydrogel bilayers act as biocompatible, flexible and environmentally responsive hinges to fold the 2D structure into a 3D conformation. To achieve this, a rapid method of producing nanopatterns with the potential for large area patterning was developed. These were fluorinated ethylene propylene (FEP) and polydimethylsiloxane (PDMS) replica stamps with 2D and 2.5D hierarchical patterns. They were capable of bending and conforming to uneven and curved surfaces. These were used in a novel combinational lithography approach to construct complex hierarchical structures by photolithography through photomasks with nanopatterned transparent FEP inlays to create unfolded 3D cellular niches by a 2D method. Several different hydrogels were synthesised and patterned by photolithography to be used as bilayer hinges. Actuation mechanisms included thermoresponsive N-isopropylacrylamide (NIPAAm), and anionic acrylic acid (AA)monomers. Successful bilayers were formed using acrylate based photochemistry with poly(ethylene glycol) dimethacrylate (PEGDMA)and pH responsive polyacrylic acid (PAA) in a novel sacrificial layer functionalisation method. These structures would bend and roll due to differential swelling in neutral pH and when acting as a hinge would result in self-folding of photolithographically defined 2D structures into 3D containers. To test the compatibility of this method of manufacture with cell culture hESCs were trialled on the container materials, and showed excellent adhesion on the SU8 structures. More ambitiously to see if they could in the future be used for the directed differentiation of stem-cells, hESCs were cultured on nanopatterned injection moulded polymer substrates with varying nanofeature type. It was found that hESEs had improved adhesion on vitronectin coated nanotopographies even at extremely low vitronectin concentrations, and showed an increased 3D colony structure leading to the enhanced expression of certain lineage markers. It was found that hESC attachment could be mediated by feature height and substrate elasticity. This work has demonstrated as a proof-of-principle, a rapid and simple method of producing nanopatterned 3D self-folding containers, compatible with cell culture which could in the future serve as 3D self-folding nanopatterned cellular niches for tissue engineering.