**1. Introduction**

Oral and maxillofacial tissues are a complex array of bone, cartilage, soft tissue, nerves and vasculature. Damage to these structures, even when minimal, usually leads to noticeable deformities. Therefore, the repair of large segmental bone defects of the jaw or mandible due to trauma, inflammation, or tumor surgery remains a major clinical problem. For many years, simple autogenic, allogenic, or xenogenic bone grafts, or combinations thereof, have been the mainstay for tissue replacement [1]. However, when large bone defects are present, advanced approaches such as free tissue transfer with microvascular reanastomosis of vascularized flaps from distant sites including the fibula, iliac crest, scapula, and radius are needed to repair or regenerate a functionally complex tissue such as maxillofacial tissue [2, 3]. While these procedures have proven to be reliable and effective, they require extended hospitalization, and a secondary donor site with the associated morbidity and complications. As an alternative to current surgical techniques or approaches, developments in tissue engineering using the gene therapy and stem cell biology strive to utilize cells, biomaterial scaffolds and cell signaling factors to regenerate large oral and maxillofacial tissues defect with precise replication of normal body contours. A tissue engineering approach offers several potential benefits, including a decrease in donor site morbidity, a decrease in technical sensitivity of the repair, and the ability to closely mimic the in vivo microenvironment in an attempt to recapitulate normal craniofacial development [1].

Mesenchymal stem cells (MSCs) derived from bone marrow have been used experimentally for tissue engineering applications [4-6]. MSCs can differentiate into several different cell types, such as those that produce bone, cartilage, tendon, and other connective tissues, as well as muscle, adipose, and dermal cells [7-10]. MSCs can be expanded in culture while maintaining their multipotency.

© 2013 Tobita and Mizuno; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The concept of prefabricated bone engineering with MSCs for large bone defects may play a pivotal role in future therapies. However, bone marrow-derived MSCs have been reported to require selective sera lots and growth factor supplements for culture expansion [11]. Further‐ more, traditional bone marrow procurement, particularly in volumes larger than a few milliliters may be painful, frequently requiring general or spinal anesthesia [12-14].

Bone marrow tissue provides the most universal and attractive source of MSCs; however, other tissues such as periosteal [15], muscle [16], synovial membrane [17] and adipose [18-20] tissues also appear to possess MSCs. Particularly, adipose tissue is an important source of stem cells because subcutaneous adipose tissue is an abundant and accessible source of both uncultured stromal vascular fraction (SVF) cells and cultured homogeneous adipose-derived stem cells (ASCs) (21). ASCs obtained from lipoaspirates have multilineage potential and will differen‐ tiate into adipogenic, chondrogenic, myogenic, osteogenic, and neurogenic cells [19, 22, 23]. Thus, ASCs have great potential for clinical applications such as the repair of damaged tissues and angiogenic therapy. Injection of human ASCs was recently shown to improve neovascu‐ larization in an ischemic hindlimb mouse model and osteoid matrix formation in immunoto‐ lerant mice [24-26]. Further, ASCs have been shown to increase the functional capacity of damaged skeletal muscle in vivo [27]. Therefore, these reports suggest that ASCs may also have the potential for use in large bone tissue engineering techniques such as prefabrication. Recently, prefabricated bone engineered with ASCs was reported both with in vivo studies in rat and a clinical human case. Thus, the use of ASCs in maxillofacial tissue reconstruction should be viewed favorably and these novel approaches may have advantages for tissue reconstruction.

In this chapter, the current approaches and the biomaterials used for repair of large bone defects are presented, and the novel approach of prefabricated bone engineering with MSCs and ASCs is introduced.
