Scaffolds with integrated properties and applications in cell transplatation

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Wang, Jinyang
Luo, Ying
Taylor, W. Robert
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Scaffolds are biomaterials serve as substrates for cell attachment and provide microenvironments for cell growth. Though they were initially designed for in vitro tissue growing applications, they are gaining increasing importance in cell therapy, where they serve as delivery vehicles of cells to overcome the low cell retention and survival resulted from delivering cells alone. An ideal scaffold for cell therapy should be optimized in multiple properties, including mechanical property, biocompatibility and 3D structures. However, traditional scaffolds were limited by their materials and fabrication techniques that they can hardly optimize multiple properties at once. Therefore, in this dissertation① three novel scaffolds with integrated properties were represented and their applications in cell delivery were demonstrated. Polyester microfibers and hydrogels are two most studied type of scaffolds. Polyester microfibers are hydrophobic. They have good mechanical property and fibrous porous structure. Hydrogels are water absorbable and usually have good compatibility. However, their application is often limited by weak mechanical strength. In the first part of this dissertation, a surface RAFT polymerization technique was developed and for the first time achieved nano-thin PEG hydrogel coating on PCL micro-fiber surface. This composite scaffold showed good macro-mechanical property and fibrous, porous structure like microfibers. Meanwhile, after integration of hydrogel, the hydrophobic scaffold became water-absorbable like hydrogels and showed improved biocompatibility. The method applied in this study could be transformed to other polyester scaffolds as well to make integrated materials. Microtissues are more likely than single cells to undergo hypoxia induced necrosis and apoptosis caused by clumping. Therefore, scaffolds for delivering microtissues should have the ability to regulate their spatial distribution. However, traditional scaffolds are usually designed to regulate cell microenvironments in nano to micro scale, such as electrospun fibers and hydrogels, and lack the ability of spatial regulation in higher magnitudes. Therefore, in the second part of this dissertation, a novel method for microtissue transplantation was demonstrated. Microwell patterns were introduced on surface of electrospun fibers through microfabrication technique. This microwell patterned electrospun fibers regulated the spatial distribution of MSC spheroids and maintained their improved paracrine function. MSC spheroids loaded microwell patterned scaffolds were further transplanted in mice with hind limb ischemia. Results showed that the microwell patterned scaffolds increased MSCs’ retention and survival and improved the vascularization of ischemic tissues. The interaction between host tissue and transplanted cells can be controlled by careful design of the scaffold structure and pore size. In the third part of this dissertation, a pore size controllable spherical hollow scaffold was designed for cell transplantation. Comparing with hydrogel beads, this novel spherical scaffold has a double layer spherical structure, better mechanical property and a wider control in pore size. MSCs can be injected inside the hollow core of scaffold for transplantation. The scaffold could improve MSCs’ paracrine function and MSCs’ retention could be controlled be different pore size of the scaffold surface.
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