Mark Appleford, Ph.D.

The focus of my current research is to examine bone cell interactions with biomaterials and to study the pathways of cell differentiation into mature tissues. To clarify cell-biomaterial interactions we examine the integrin receptor activity of cells during their first contact with a biomaterial. Sub-cellular signaling pathways have been identified to track key players such as the stress activated protein kinases (SAPK), viability markers such as P38 and differentiation gene transcription factor RUNX2. By following pathways from outside the cell, through internal protein signaling and finally to the production of specific proteins by the cell, we can help explain the mechanisms responsible for implant rejection or successful long-term integration. Most research in this field has been performed with experiments of 2D cell monolayers. Our laboratory has developed a variety of techniques to measure these signals within 3D scaffolds to better understand the mechanisms of cell behavior. The laboratory also explores the tissue-level formation of new bone through the use of bioreactor tissue engineering. Fluid perfusion chambers have been used to grow volumes of bone tissue in the laboratory for up to three months. By studying the morphology of the new tissue we can help refine ideal culture conditions for replacement grafts while identifying the precise fluid shear mechanical forces associated with differentiation pathways.

In addition to these basic science approaches, the laboratory works on the large scale reconstruction of bone and cartilage tissue using natural ceramic scaffolds. Calcium phosphate foams serve as a template for bone bridging of large segmental defects in the cranium, femur and tibia. The approach of this research has been to bridge a large defect for early integration while still allowing for natural blood vessel and bone formation that ultimately replaces the scaffold within a year.

Areas of Research Interest:

• Protein signaling of mechanotransduction in bone cells
• Bone reconstruction following osteosarcoma and severe trauma
• Investigation of angiogenesis applied to tissue engineering strategies
• Experimental and theoretical mechanical behavior of orthopedic implants and tissue-material hybrids