Design Biomimetic Microenvironment for Stem Cells

A key area for the use of electrospun nanofiber is in tissue engineering for various tissue and organs. Since the basic structural support of natural extracellular matrix (ECM) consists of collagen fibers and fibrils with nanometer scale diameter, many researchers are turning to electrospinning to fabricate the ideal ECM in tissue replacement. Researches has shown that by using electrospun fibers with its ECM-mimetic nanotopography, certain signal transduction pathways vital in normal cellular activity can be activated in the absence of chemical cues. Electrospinning offers many advantages over other methods of fabricating ECM. Other then its ability to fabricate nanometer diameter fibers, it can be used in a range of materials to produce nanofibers. Synthetic non-biodegradable polymers, biodegradable polymers, natural polymers, composites and even ceramic nanofibers have been electrospun. Although typical electrospun fiber scaffold is in the form of a 2-dimensional non-woven fiber mesh, other assemblies such as aligned fibers scaffold and tubular scaffold can be made through modification of the setup.

In a typical electrospinning setup, a high voltage power supply is used to apply a high voltage to a solution of sufficient viscosity. A grounded collector is then used to collect the random two-dimensional mesh of nanofibers. With modification of the electrospinning setup, it is possible to obtain aligned fibrous assemblies and tubular nanofibrous structures. However, when it comes to the fabrication of a truly three-dimensional architecture, researchers faced several difficulties, in particular the difficulty in handling the nanofibers. This may result in the lack of three-dimensional structures made up of pure nano-dimension materials. In our studies, we have demonstrated a promising method of obtaining three-dimensional nanofibrous architecture. Using fluid as a supporting medium, it may be possible to indirectly “handle” the nanofibers and model the nanofibers to form three-dimensional nanofibrous architectures. Furthermore, we have developed novel processes for mineralization of electrospun nanofibers to form a mineralized nanofibrous composite similar in structure to that of natural bone.

Our group has conducted pioneer research on cell-nanofibers reactions. These observations indicate that nanofiber scaffolds positively promote cell-matrix and cell-cell interactions, inducing them to express the normal phenotypic shape. In summary: (a) nanofibers significantly promote cell adhesion, proliferation and differentiation; (b) The orientation of aligned nanofibers guides the orientation of cytoskeletal proteins; (c) functionalized nanofibers can enhance the above mentioned effects of nanofibers on cell behaviors.

Recently, stem cell research become hot topic since it has the potential to benefit millions of people around the world requiring replacement or renewal of tissue function. The bone marrow contains at least two kinds of stem cells, the hematopoietic stem cells (HSCs) and bone marrow derived mesenchymal stem cells (MSCs). Our experimental results demonstrate that it is possible to capture HSCs and MSCs on collagen or collagen coated nanofibers in less than 30 minutes under ambient condition. This exciting finding suggests the possibility of capturing critical numbers of stem cells on our nanofibrous scaffold, eliminating the need for a separate in vitro culture procedure to expand the number of MSCs. The positive interaction of MSCs and 3D nanofibrous scaffold is a key positive factor in our attempt to construct biomimetic and bioactive synthetic ECM/cells composite for tissue regeneration.

Based on these foundations, our healthcare group works closely together to provide more solutions to address unmet medical needs for:

Skin Regeneration

Bone Regeneration

Cardiac Regeneration

Cartilage Regeneration

Surface Modification for Implants

Nerve Regeneration

Stent

For possible collaborations and more enquires on these projects, please contact:

Dr Susan Liao

mpesl@nus.edu.sg