ABSTRACT
Tissue-engineered bone constructs offer a potential solution to the limitations associated with bone grafts. This approach to tissue regeneration typically combines biological and synthetic components to create implantable constructs that recapitulate native tissue function and/or stimulate tissue repair [79]. Constructs combining osteogenic cell populations, osteoinductive signaling factors, and osteoconductive scaffolding materials hold the potential to harness each of the positive qualities associated with autologous bone grafts. In fact, bone tissue substitutes combining various osteoconductive materials (e.g., polymers, ceramics, allogeneic bone matrix) with osteoinductive recombinant growth factors (e.g., bone morphogenetic protein-2 (BMP-2), transforming growth factor-ß (TGF-ß)) have demonstrated utility as bone defect fillers and comprise a vast array of commercially available therapeutic products [80]. While growth factor-based approaches to bone regeneration have demonstrated some clinical promise, limitations to this method include the high cost of recombinant protein production, lack of control over protein release kinetics, and the potentially harmful supraphysiological quantities of proteins required to induce a host tissue response [81,85,116]. In addition, the success of growth factor-based constructs is dependent upon the availability of endogenous cell populations, creating a potential challenge for patients lacking sufficient numbers of responsive cells.Bone tissue substitutes incorporating osteogenic cell popula-tions have the potential to directly participate in bone tissue
formation immediately following implantation. In addition, implanted cell populations secrete biological factors in a more physiologically relevant manner through their interaction with the surrounding microenvironment. Stem cells, commonly characterized by the capacity for self-renewal and the potential to differentiate into multiple cell types, provide an exciting source of implantable osteogenic cells that can be isolated from autologous or allogeneic sources, as well as expanded to clinically relevant numbers ex vivo. The purpose of this chapter is to introduce the reader to current research utilizing stem cells for the purposes of bone regeneration. The potential for a number of different stem cell populations to be utilized in therapies directed at bone formation will be discussed. As stem cell differentiation is modulated by both biochemical and physical microenvironmental cues, we will also describe several current approaches to direct stem cells toward a bone-forming phenotype. More specifically, the spatiotemporal presentation of micro-and nanoscale stimuli to stem cells via soluble factors and cell-surface interactions will be addressed in detail. Finally, the ability of cell-based bone tissue constructs to generate new bone tissue, both in vitro and in vivo, will be discussed, along with some of the hurdles remaining to develop synthetically engineered bone tissue substitutes that rival their autologous counterparts. 14.2 Sources of Stem Cells for Bone
Stem cells, defined as undeveloped cells capable of self-renewal and differentiation into multiple phenotypes, play a vital role in the development and regeneration of human tissues [134]. These cells can generally be categorized into two groups: pluripotent stem cells (PSCs) and adult stem cells. Pluripotent stem cells, representative of an early stage of embryonic development, have the capacity to differentiate into virtually all mature cell populations. Adult stem cells, on the other hand, possess limited differentiation potential and are present in a wide variety of adult tissues, carrying out day-to-day tissue repair. Here we give a brief introduction to each type of stem cell, discuss their advantages and disadvantages for cell-based therapies, and analyze how they can be utilized in regenerative medicine approaches toward bone repair.
