Complex nanofibrous scaffolds encapsulated with growth factors and incorporated with cells for human tissue regeneration

Abstract

Abstract of thesis titled Complex Nanofibrous Scaffolds Encapsulated with Growth Factors and Incorporated with Cells for Human Tissue Regeneration Submitted by Zhou Yu for the degree of Doctor of Philosophy at The University of Hong Kong in August 2017 Tissue loss or dysfunction caused by trauma or disease is a major medical problem that threatens human health and life. Tissue transplantation has been used for solving this problem but it is limited by donor shortage, immunological rejection and possible transmission of diseases. Therefore, new strategies are pursued to overcome the drawbacks of transplantation and to promote new tissue formation in human bodies. Tissue engineering holds great promise to solve the major problems in tissue loss or dysfunction. It develops biological substitutes for regenerating human body tissues. Electrospinning can produce nanofibrous scaffolds which resemble the extracellular matrix of body tissues. However, conventional electrospun scaffolds have limitations such as small pore sizes. Furthermore, the release behavior of drugs or biomolecules from scaffolds made by conventional electrospinning is generally undesirable. To produce delivery vehicles for drugs and biomolecules, electrospray has been investigated. The aim of this project is to investigate advanced nanofibrous scaffolds which would be fabricated by a novel technology for the regeneration of complex body tissues. A method for enlarging pore size in electrospun scaffolds was also studied. Controlled release of drugs or biomolecules from scaffolds would be achieved through emulsion electrospun nanofibers.

A hybrid technique which combined electrospinning with phase separation was investigated for increasing the pore size of electrospun scaffolds. Electrospun fibers were deposited into a fiber collector filled with ice water, ice methanol or liquid nitrogen for achieving phase separation. The pore size of electrospun scaffolds thus made was moderately increased.

Emulsion electrospinning was studied for fabricating nanofibrous delivery vehicles for drugs and biomolecules in comparison with blend electrospinning. Drug or biomolecule released from blend electrospun scaffolds showed low encapsulation efficiency and severe burst release. Higher encapsulation efficiency and more controlled release of drug or biomolecules were achieved through emulsion electrospun scaffolds. Furthermore, dual delivery of drug and biomolecules was possible using bicomponent or bilayer emulsion electrospun scaffolds.

Emulsion electrospray was employed to produce microspherical delivery vehicles for biomolecules. Sustained and steady release of biomolecules was observed from these electrosprayed microspheres. Coaxial electrospray with post-spray crosslinking was investigated for live cell encapsulation. Using coaxial electrosprayed core-shell structured microspheres, high cell encapsulation efficiency could be achieved and cell viability could be well preserved. The release of cells from electrosprayed microspheres could be controlled.

A novel technology of concurrent emulsion electrospinning and coaxial electrospray was developed to produce growth factor-encapsulated and cell-laden nanofibrous scaffolds. Endothelial cells or smooth muscle cells released in nanofibrous scaffolds exhibited high cell viability. Growth factors released from nanofibers in scaffolds enhanced cell proliferation and differentiation. This fabrication technology was further used to make growth factor-encapsulated and cell-laden multilayered scaffolds with different cells and growth factors in different layers. The endothelial cells and smooth muscle in bilayer scaffolds maintained high viability and their proliferation was promoted by released vascular endothelial growth factor and platelet-derived growth factor, respectively. The advanced complex scaffolds encapsulated with growth factors and incorporated with cells fabricated by the novel technology are highly promising for the regeneration of complex human body tissues.