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Over 40% of the disabling medical conditions of persons aged 18 years and over are musculoskeletal related. This number is even higher within the older population (Weinstein, 2000). Surgical treatment for age-, traumaor cancer-induced critical-size bone loss is particularly challenging. Current grafting material options for scaffold-assisted surgical repair of critical-size bone loss include autogenic bone grafts (autografts), allogenic bone grafts (allografts), and synthetic bone substitutes. Still considered as a golden standard, autografts, retrieved from patients’ own skeleton, are used in approximately 50% of all orthopedic bone grafting procedures. Complications arising from possible donor-site morbidity and insufficient grafting materials are major drawbacks of autografting procedures (Bostrom & Seigerman, 2005). In addition, this option is highly limited within the aging population as the elderly are less likely to be qualified for such a procedure due to higher incidences of osteoporosis and metabolic diseases. Allografts, obtained from another human donor or animal cadaver, represent a useful alternate to autografts, and are used in approximately 40% of bone grafting surgeries. However, allografting procedures suffer from risks for rejection and disease transmission, and a significant structural failure rate due to poor tissue integration, both structurally and biochemically (Blokhuis & Lindner, 2008; Bostrom & Seigerman, 2005; Eagan & McAllister, 2009; Goldberg & Stevenson, 1994). These limitations, along with the growing aging population, has led to an increasing need for viable synthetic bone substitute alternatives (Salgado et al., 2004). Current clinically used synthetic bone grafts such as brittle ceramics and weak gel foams are used in only ~10% of all bone grafting procedures (Bostrom & Seigerman, 2005), primarily due to their unstable graft fixation and insufficient tissue-graft interactions (Carson & Bostrom, 2007; Goldberg & Stevenson, 1994; Place et al., 2009; Stevens, 2008). In the past two decades, many new synthetic bone grafts designed to mimic key structural and biochemical properties of bone to enhance osteointegration and graft healing have emerged in literature. This rapidly evolving field has been extensively reviewed by others, including broad overviews of current requirements and techniques for preparing synthetic bone grafts (Burg et al., 2000; Salgado et al., 2004), calcium phosphate–based bone substitutes (De Long et al., 2007), polymeric bone substitutes (Seal et al., 2001), and biomimetic nanocomposite orthopedic biomaterials (Chan et al., 2006; Murugan & Ramakrishna, 2005). This chapter highlights the evolvement of non-metallic orthopedic biomaterials from bioinert,

Scalable Functional Bone Substitutes: Strategic Integration of Key Structural Elements of Bone in Synthetic Biomaterials