Construction Of Micro-Structure With Shape Memory Properties For Application In Biomedcine

With the development of science and technology, the living condition of human become better and better and more attention has been paid to the health problem of human. Under this background, shape memory polymers (SMPs), a new type of functional materials, have been receiving more and more attention in biomedicine. Despite the SMPs possess the property of dynamic deformation, which can effectively mimic the naturally dynamic cellular environments and is very important for tissue engineering, however few researches about the application of SMPs in tissue engineering have been reported.In this paper, we did some preliminary exploration in construction of various micro-structured biomaterials with shape memory properties at near physiological temperature by using biocompatible poly(?-caprolactone). These micro-structured materials, including composite nanofibers, micropattern, and microspheres, were fabricated through electrospinning, thermal embossing microimprint lithography, and traditional double emulsion/solvent evaporation method. Furtherly, we try to explore the application of SMPs micro-structures in biomedicine by cells experiment and animals experiment. These works may provid some theoretical basis for MSCs differentiation on the dynamically tunable surface and the design of novel tissue engineering scaffolds.In the second chapter, one class of biodegradable polymer composite nanofibers was fabricated with an electrospinning process using chemically cross-linked poly(?-caprolactone) (c-PCL) as the matrix and multiwalled carbon nanotubes coated with Fe3O4 nanoparticles (Fe3O4@CD-M) as a magnetism responsive source. The shape memory effect (SME) of c-PCL is still attributed to thermal induction, which can be triggered by the heat generated from Fe3O4 nanoparticles in an alternating magnetic field via hysteresis loss, and the MWNTs are considered as a excellent conductors of heat. Alamar blue assay was performed from culturing osteoblast populations to evaluate the cytotoxicity. The result showed that the electrospun composite fibers possessed good biocompatibility and could be applied in biomedical fields.In the third chapter, a thermally switched two-way reversible shape memory micrometer-sized sphere was fabricated with raditional double emulsion/solvent evaporation method on the basis of a biocompatible and biodegradable polymer network containing well-defined six-arm poly(ethylene glycol)-poly(?-caprolactone) (6A PEG-PCL). The particles with an ellipsoidal temporal shape were achieved by PVA film stretching at 60? with subsequent cooling to 0?. The reversible shape memory recovery between spherical and ellipsoidal shape was realized with the cyclic heating and cooling between 43? and 0?. In particular, macrophages were used as a model cell for the investigation of the internalization of these particles and subsequently intracellular shape memory recovery.In the fourth chapter, a dynamic micro-well substrates were fabricated via thermal lithography with arrays of triangle-, square-, hexagon- or round-shaped micro-wells, which were made of biocompatible and biodegradable polymer network containing six-arm poly(ethylene glycol)-poly(s-caprolactone) (6A PEGPCL) with excellent thermally activated shape memory function. The dynamically tunable geometric micro-wells and the resulting mechanical force effectively and significantly regulated the cytoskeletal structure and tension of rBMSC in vitro without induction media when compared with the static patterned. Cellular and molecular analyses revealed that cells cultured in various dynamic micro-wells had disparately differentiated along adipogenesis and osteogenesis pathways. We further implanted these dynamically tunable geometric micro-well substrates into the site of rabbit mandible defect and found that they prompted differentiation of mesenchymal stem cells into osteogenesis and in turn efficiently repaired the mandible bone defect.In the fifth chapter, we present a strategy to effectively regulate stem cell differentiation with dynamically tunable surface microgrooves. Unlike in the static system, stem cells can feel more complex signals in the dynamic microenvironment close to natural cellular environment. The surface microgrooves were fabricated by a novel thermal controlled four-stage SMP, which allows dynamic yet fine-tuning of the surface microstructure. The width of the stretched surface microgrooves is decreased gradually due to the shape recovery as temperature increases from 32 to 41?, which leads to alignment of patterned cells and thus makes the cytoskeletal arrangement more compact in comparison with cells on a static substrate. The results obtained from the gene expression and western blot analysis further revealed that the stretched and longitudinal cell shape appears to be conducive for myogenic differentiation gene expression for stem cells on dynamically tunable surface microgrooves in the absence of any induction factors.