The goal of regenerative medicine at the HMRC is to produce functional tissue replacements to repair or replace damaged tissue. Our main focus is centered on bone and joint tissues, such as: articular cartilage, the intervertebral disc, and ligaments. These tissues are known for their limited capacity for self-repair, and are perfect candidates for regenerative medicine applications.
Research conducted within the HMRC covers a wide variety of regenerative medicine techniques in order to produce functional tissue replacements. These include the design, synthesis and characterization of new polymer biomaterials, the design of cell/tissue scaffolds, the development of tissue-specific bioreactors, and applied stem cell biology to engineer new cell-based therapies.
What is Tissue Engineering?
Tissue engineering is the development and manipulation of laboratory-grown molecules, cells, tissues, or organs to replace or support the function of defective or injured body parts. Tissue engineering holds great promise for the treatment of numerous diseases, disorders, and traumas. The long-term objective in the field is to create tissue substitutes that will fully integrate into the body, promoting regeneration and restoring lost function.
Tissue Engineering using Adipose-derived Stem Cells
One common approach is to seed a supporting scaffold with cells that will contribute to the developing tissues while defining and maintaining the desired three dimensional shape. Adipose tissue (fat) may be an ideal cell source for tissue engineering, as most patients are able to donate a small sample for cell isolation without any adverse effects. As well, using the patient's own cells avoids problems with immune rejection. Adipose-derived stem cells (ASC) are a population of multipotent mesenchymal stem cells and more-committed progenitors that are found within fat.
In the lab ASC proliferates rapidly and can be stimulated to differentiate into mature fat, muscle, bone and cartilage cells, as well as a putative neuronal population. Researchers are developing systems to culture the ASC, while maintaining their stem cell capacity, in order to obtain clinically-relevant cellular populations. Working collaboratively researchers are investigating the ASC population within naturally derived and synthetic scaffolds for adipose tissue engineering purposes, including the development of new approaches in cartilage, bone and cardiac tissue engineering. The aim of tissue engineering strategies using ASC is to create functioning, healthy tissues that are fully integrated into the host system. Towards the development of a tissue-engineered adipose substitute, research is focused on adipose-derived stem cells (ASC) and naturally derived biomaterials.
Naturally Derived Biomaterials
Normal cellular organization and behaviour are mediated in part by interactions with the extracellular matrix (ECM), the scaffolding material that is naturally found, in varying forms, within all tissues. Matrix producing cells in the body secrete and degrade ECM components, including multiple forms of the protein collagen. Cell binding to the ECM can impact a range of cellular responses including proliferation, differentiation, migration, and apoptosis (programmed cell death). The ECM plays an essential role in processes such as embryonic development and would healing.
Scaffolds derived from the ECM hae been investigated for a rang eof tissue engineering applications. ECM-based biomaterials can facilitate normal cell-matrix interacts and have been shown to promote in vivo regeneration. Moreover, cellular processes such as proliferation, migration and differentiation can be modulated by the scaffold composition and architecture.
Mechanical stimulation of cells and mechanical conditioning of the developed tissue
Attempts to engineer functional connective tissues in vitro have not proven to be entirely successful. Recent studies have demonstrated that physical forces, in part, play an important role in both the development and maintenance of these issues in vivo. For this reason we have been investigating whether the application of dynamic mechanical forces (e.g. compression, shear) can accelerate tissue growth and improve the mechanical performance of the developed tissue. Similarly, researchers are currently investigating the effect of high frequency vibrations during the grown of engineered cartilage, ligament, meniscus and the intervertebral disc.
Cell and tissue stimulation device (Mach-1) used to study the effects of:
Influence of Nutrient Supply on Tissue Formation
There is increasing evidence that the supply of nutrients is a limiting factor during in vitro tissue development. As well, in certain connective tissues, a decline in the nutrient supply has been implicated in tissue degeneration in vivo. This study is directed at the interplay between different energy metabolism pathways and the synthesis of extracellular matrix macromolecules by various types of connective tissue cells (chondrocytes, fibroblasts, etc.).
Perfusion bioreactors for tissue-engineering
Bioreactors have gained increasing importance in tissue-engineering to provide the conditions necessary for the cells to regenerate functional tissue. Researchers at HMRC have recently developed a novel perfusion bioreactor and they are currently investigating the effects of both the hydrodynamic and biochemical environment on the growth of engineered connective tissues.