This thesis investigates the factors influencing bone remodeling within the human skeleton with a focus on developing methods for constructing prosthetic bone scaffolds containing cells to progenerate into living bone upon implantation in the body. These porous scaffolds would ideally regulate events such as cellular proliferation and intracellular signaling after surgical implantation. The overarching goal is to identify materials, geometries, and other properties of the scaffold design in order to generate replacement tissue that replicates the original bone structure and geometry.
Bone remodeling is the process of simultaneous removal of old bone and replacement with new bone powered by the coupled actions of osteoclasts and osteoblasts, cells that resorb bone and produce bone, respectively. While bone remodeling occurs more intensely during skeletal development, it continues throughout a human's lifetime, repairing microscopic damage resulting from stress and fatigue on the body. There are many different models that describe how remodeling may occur as well as what initiates the remodeling response to damaged bone.
Historically, biologists explored tissue development primarily in terms of chemical and electrical signal pathways controlled by genes. However, recently published studies have implied that bone cells may be able to sense and react to mechanical forces. These forces likely have a crucial role in stimulating remodeling to occur based on the existing three-dimensional geometry of the bone and how well suited it is to handle the forces. Many independently published studies have investigated singular mechanical factors in the stimulation of bone remodeling as well as the resulting implications for the design of implanted skeletal scaffolds. However there remains a lack of publications that analyze multiple studies in order to examine their similarities and discrepancies. Reviews linking multiple studies are valuable tools for moving bone engineering theories into practical realities.
Based on the hypothesis that stresses that develop among bone cells are control mechanisms in regulating bone remodeling, a literature search was conducted. Two critical factors were examined in detail: the effects of pore geometry and the stiffness of the substrate on the rate and concentration of cell proliferation. Experimental results of conducted studies as well as theoretical results using finite element analysis and analytical equations were compared and contrasted. Finally, conclusions were synthesized from each study into general observations that are important to the future creation of bone scaffolds.