The success of tissue engineering for cartilage for conditions like osteoarthritis will be dependent on the interactions between the cells, the matrix, and mechanical forces directed against the joint.
The extracellular matrix- the framework and the material inside the framework the stem cells cling to- plays a crucial role in tissue function, dictating its physical and mechanical properties, maintaining the spatial arrangement of the cells that live within it and controlling the complex crosstalk that exists between the cells, the matrix and external forces. The matrix controls cell size, shape, movement and alignment through its three-dimensional architecture and adhesion... the stickiness of the stem cells.
While the matrix exerts its effects, the cells influence the matrix by applying traction forces and by synthesizing and degrading matrix. In addition, the interaction between the matrix and stem cells is responsible for triggering a variety of specific cellular functions. It has become increasingly clear that the mechanical environment is equally important as, and synergistic with, the chemical environment in directing cell behavior.
Signaling pathways spurred on in response to mechanical (load-bearing) forces are essential for the maintenance and function of tissue cellular function. Load-bearing soft tissues such as tendons and cartilage which consist of a network of fibrous protein (predominantly collagen and elastin), embedded in a gel of proteoglycans, glycosaminoglycans and glycoproteins exhibit specific properties of tissue biomechanics and subsequent cellular responses.
Investigations in these unique tissues and engineered are rapidly expanding our understanding of a new area of medicine called mechanobiology.
Successful tissue engineering requires a comprehensive understanding of mechanobiology and in particular the loading conditions experienced by the cells under physiological conditions, in order to establish how this controls cellular functions.
Clarification of mechanical pathways should provide useful information for tissue engineering and regenerative applications as well as further insight into mechanisms involved in disease processes.
The population of the Western world is aging. As a direct consequence, there will be an increase in diseases that can be associated with aging, such as joint problems.. Those maladies not only have a negative effect for the patient, but will also have a significant impact on the health care system. Therefore, it is extremely important that more active, less traumatic and less expensive methods and techniques are developed for the treatment of these diseases. The expectation is that nanotechnology will provide an important contribution to the development of such techniques. Implants and tissue substitutes are made from biomaterials that have one common property, i.e. biocompatibility. A promising application of nanotechnology is the development of better functioning biomaterials.
A recent approach to the design of next-generation tissue regeneration supporting biomaterials is focusing on the structure at the "nano" scale. The underlying idea is that nanometer structure matches with the natural extracellular matrix resulting in an improved interaction of the tissue-forming cells compared with conventional biomaterials. Recent developments in the field of nanotechnology offer powerful tools to modify the surface of biomaterials by introducing artificial mapping and specific surface chemistry on the material. It is well-known that both topography and surface chemical composition affect the reactions of the biological environment to the device.
Human mesenchymal stem cells occupy a particular stem cell niche, and consist of those stem cells that can differentiate into cells of mesenchymal tissues, including osteoblasts, adipocytes and chondrocytes.
Osteoarthritis is the most common musculoskeletal disorder and causes a significant social and psychological drain on those affected as well as those who care for them; in addition it leads to significant economic costs. This disease is characterized by articular cartilage degeneration and damage to the underlying subchondral bone. To date, there is a lack of effective therapies to treat the disease, resulting in total joint arthroplasty (joint replacement surgery) as the only viable therapeutic option. Thus, there is a need to develop methods that are less invasive and capable of regeneration of articular cartilage.
The use of autologous chondrocytes in tissue engineering applications promises an avenue in terms of efficacy and safety resulting in mesenchymal stem cells (MSCs) being considered an ideal therapeutic candidate for cartilage repair. MSCs acting through multiple growth mechanisms are also known to prevent OA progression after injection into the joint.
At our center, we are constantly incorporating newer approaches to the introduction of stem cell technology for the treatment of osteoarthritis.
Our approach now is different from the way it was a year ago... and it will be different a year from now as we learn more about nanobiology.
