Tissue engineering is a truly multidisciplinary field which applies the principles of life science, engineering, and basic science to the development of viable substitutes which restore, maintain, or improve the function of human tissues. Modern isolation and culturing techniques of any type of human cells including fibroblasts, keratinocytes, chondrocytes, osteoblasts, endothelial and mesenchymal stem cells provide the basis for tissue engineering. Naturally derived or synthetic biomaterials are fashioned into scaffolds which when cultured and implanted in combination with cells provide a template that allows such constructs to form new soft and hard tissues during which time the scaffold gradually degrades and is finally metabolised. Based on this tissue engineers, the Department focus on the following core capabilities:


    1. Design, Fabrication and Characterization of Scaffolds

    2. Cell Isolation, Proliferation, Differentiation and Characterization (including stem cells)

    3. Control Drug Release Technology

    4. Bioreactor Design

    5. Transplantation Technology


The term “Tissue Modulation” was coined to characterise a research direction that aims to positively influence the development, composition and stability of tissue by manipulating its extracellular matrix content or altering the phenotype of progenitor cells. To achieve these aims the Laboratory employs well defined non-peptide based synthetic small or very large molecules.

The Laboratory has implemented four biomedical research lines:

Matrix Enhancement - Collagens and related ligands are major components of the connective tissue of tissues like skin, blood vessels, tendon and bone. Obviously, the in-vitro production of these tissues requires substantial amounts of deposited and biologically crosslinked collagens. The Laboratory is currently characterising polymeric culture medium additives that accelerate the enzymatic conversion of procollagen to collagen and its crosslinking that lead to a stable enhanced matrix formation in tissue engineered constructs.
 

Scar Wars - The Laboratory is leading the NMRC-funded National Group on Fibrovascular Disorders Programme (NFDP) to explore antifibrotic substances for the treatment of scarring conditions of several tissues.
 

Biological X-linking and Mechanics - “Collagen-inspired Biomaterials” focuses on stabilisation of collagen-blended nanospun fibers and the incorporation of tagged bioactive peptide sequences as crucial reaction partners for cells and tissue.
 

Manipulation of the Stem Cell Phenotype - We aim to model cell free stem cell niches to control aspects of stem cell properties in-vitro. A “stem cell niche” is a 3D environment of cell subsets and extracellular matrix (ECM) that can indefinitely house stem cells and direct their self renewal and production of progeny. We want to focus on the isolated effects of the ECM on adult human stem cells. To achieve our objectives we will use technology achieved from our ECM platform, namely the creation of biological ECMs derived from different cell types and use their deposited ECM to 1) control niche specific stem cell properties (niche effect) and 2) direct differentiation into niche specific cell types particularly of CNS lineages (niche-specific differentiation).


Tendons and ligaments are among the most frequently injured organs in the young and active population. These injuries are associated with poor healing and incomplete recovery. The Tissue Repair Lab focuses on regeneration of ligament/tendon using various tissue engineering approaches like designing optimal biopolymer scaffolds, investigating cell delivery systems and building advanced bioreactors for mechanical stimulation of the growing tissues.

Scaffold

“Nano-microscaffods” were fabricated by electrospinning nanofibres on microfibrous knitted scaffolds, combining the advantages of good mechanical strength of the microfibers and very high surface area and porosity of the nanofibers. Moreover, such scaffolds could be easily seeded by pipetting cell-suspensions (thus eliminating the need of fibrin gel as cell-delivery system) and bone marrow precursor cells could proliferate well and differentiate into tendon and ligament lineages.


Cell-Sheet Technology

Fibroblasts and bone marrow cells have been grown into 3-D cell-sheets and assembled with knitted scaffolds to engineer connective tissues, possessing favorable ECM production, histological and mechanical properties.


Interfacial Tissue Engineering

"Enthesis" or the bone-ligament interface would be engineered through a biomimetic approach following the same steps in vitro as occuring during the development of the enthesis organ in vivo to construct a bone-fibrocartilage-ligament graft. Such a hybrid graft promises to aid in severe ligament injuries through its regeneration as well as providing adequate insertional strength.


Advanced Bioreactors

Cyclic mechanical stimulation has been shown to induce in vitro differentiation of precursor cells into tendons and ligaments. Cell-seeded scaffolds strained in the bioreactors show better cell proliferation with cells assuming an elongated morphology resembling tenocytes, and expressing tendon/ligament specific extracellular matrix. Several prototypes including standalone bioreactors and perfusion bioreactors have been developed for various tissue engineering applications.

Graphical illustration showing the principles underlying scaffold-based tissue engineering. A scaffold or matrix, living cells, and/or biologically active molecules are used in variable strategies to form a “tissue-engineered construct (TEC)” to promote the repair and regeneration of tissues


Biomaterials are synthetic or natural materials that can replace or augment tissues, organs or body functions. There is a need to develop the next generation of biomaterials and medical implants. New avenues of scientific inquiry may enable the development of biomaterials that are safe, reliable, "smart", long-lasting, and perform ideally in their respective biological environments.

In the Biomaterials Laboratory, the main objective of our research is to develop state-of-the-art next generation polymer-based nanomaterial with controlled geometry, orientation, chemical composition, and specific internal and surface molecular structures for potential applications in tissue engineering and regeneration. The electrospinning method is chosen for processing nanometer scale polymer fibers because it has a high potential to produce a variety of continuous nanofibers with different nano- and micro-structural features.

Our focus is to develop 3-dimensional scaffolds for blood vessel and nerve regeneration, hepatocytes culture, biocomposites-modified nanofibers for bone graft, and wound dressing from collagen-modified nanofibers. We have undertaken to study fundamentally cell-synthetic ECM interactions in the areas of cell morphology, gene expression and function, cell signaling, and secreted ECM profiles. We were among the first groups which demonstrated that human coronary artery smooth muscle cells and endothelial cells proliferate well on nanofibers, extension of neurites of neural stem cells cultured on nanofibers and in-growth of axons in transplanted nanofiber nerve guide conduits. We also showed the integration of hepatocyte spheroids on nanofiber mesh, human osteoblasts growth on calcium-composite nanofibers, and growth of human dermal fibroblast on collagen scaffold for wound dressing. An in-depth understanding of cell behavior cultured on nanofibers is essential to allow us to tailor the fabrication of matrices for specific applications.


Cells are surrounded by various nano-scaled topographical and biochemical cues in their microenvironment during the natural tissue development. An ideal scaffold for tissue engineering application should mimic the natural microenvironment for natural tissue and present the appropriate biochemical and topographical cues in a spatially controlled manner. Recent findings underscore the phenomenon that mammalian cells do respond to nanoscale features on a synthetic surface. Our previous studies show nanotopography can significantly influence cellular behaviours ranging from attachment to proliferation and differentiation. The understanding of how each of these two cues could influence the stem cell behaviour would aid the development of the next generation scaffold for tissue engineering and stem cell applications. We are interested to investigate the underlying mechanobiology of nanotopography-induced cell behaviour and to apply this knowledge to direct stem cell differentiation and in tissue engineering applications

   
  Applications of Nanotopography in Neuronal
Regeneration
Stem Cell and Nanotopography Interaction