Projects

• Tissue Engineering of Cartilage Using Periosteum

  Our long-term objective is to develop a tissue engineering approach for cartilage repair using periosteum (the soft tissue that covers the outside of all bones). Periosteal grafts have the potential to contribute to each of the three requirements for tissue engineering (scaffold, cells, growth factors), and have been used successfully in biological resurfacing for the repair of damaged joint cartilage. The principle obstacle to overcome for the use of periosteal tissue grafts for tissue engineering is the declining cartilage growth potential of periosteum with increasing age of the patient. We are examining the potential for pretreatment of periosteum with known cartilage-inducing growth factors to enhance (1) the number of chondrogenic precursor cells in periosteum in vivo, (2) the in vitro cartilage growth potential of periosteum and (3) the potential of periosteum to repair articular cartilage defects.

• Mechanical Factors in Cartilage Repair

  Motion is as essential for joints as joints are for motion. Mechanical factors are important in chondrogenesis, whether it is during fracture healing or cartilage repair. Continuous passive motion creates a sinusoidal oscillation in the intra-articular pressure, and significantly enhances the quality of cartilage regeneration following periosteal transplantation. However, the mechanisms by which undifferentiated mesenchymal cells in periosteum detect their mechanical environment, and the cascade of events that eventually result in production of cartilage are unknown. Our projects in this area of study focus on unraveling the relationship between mechanical factors and the stimulation of cartilage growth.

• The Role of IGF-1 Axis Genes in Periosteal ChondrogenesisWe are conducting gene expression of the key players in the IGF-1 pathway during cartilage formation in periosteum. This is an important step in helping us to understand how and especially when IGF-1 is regulated during this process and therefore at what stage or stages of the cartilage repair process it is most important. This knowledge may eventually allow us to design interventions that would improve the clinical application of periosteal transplantation for cartilage repair.
  
  
• Development of a Biologic Prosthesis for Cartilage Repair

  We are developing a biologic prosthetic composite using periosteum and various porous scaffolds. When cultured under chondrogenic conditions, the composites form a robust hyaline-like cartilage outgrowth that is attached to the porous scaffold by fibrous tissue ingrowth. The mechanical properties of these composites are similar to normal osteochondral plugs after only six weeks in culture. We feel that these scaffold/periosteum composites will be useful for the repair of major osteochondral defects. Additionally, this concept may be applicable with other cartilage-generating sources than periosteum. If successful, the implications of this approach would be great in terms of the number of patients affected and the quality of life for each of those patients.

• The Role of Wnt Signaling in Periosteal Chondrogenesis

  The Wnt pathway is one of many mechanisms through which cells communicate with each other. Wnt is important for skeletal development and the skeletal response to mechanical load (external physical forces on bone). It also plays a role in determining how stem cells, which have the capability of becoming any cell in the body, become cartilage cells. We are conducting experiments to examine how the cartilage making process in periosteal tissue is affected by growth factors like TGF- b and the way in which the Wnt signaling process affects this. We are in the process of determining the role of Wnt signaling on chondrogenesis and to apply this knowledge to tissue engineering approaches. This project also has the long-term potential to impact our understanding of degenerative joint diseases, and provide new ways to treat damaged cartilage by manipulating stem cells.