Current state of fabrication technologies and materials for bone tissue engineering.

A range of traditional and free-form fabrication technologies have been investigated and, in numerous occasions, commercialized for use in the field of regenerative tissue engineering (TE). The demand for technologies capable of treating bone defects inherently difficult to repair has been on the rise. This quest, accompanied by the advent of functionally tailored, biocompatible, and biodegradable materials, has garnered an enormous research interest in bone TE. As a result, different materials and fabrication methods have been investigated towards this end, leading to a deeper understanding of the geometrical, mechanical and biological requirements associated with bone scaffolds. As our understanding of the scaffold requirements expands, so do the capability requirements of the fabrication processes. The goal of this review is to provide a broad examination of existing scaffold fabrication processes and highlight future trends in their development. To appreciate the clinical requirements of bone scaffolds, a brief review of the biological process by which bone regenerates itself is presented first. This is followed by a summary and comparisons of commonly used implant techniques to highlight the advantages of TE-based approaches over traditional grafting methods. A detailed discussion on the clinical and mechanical requirements of bone scaffolds then follows. The remainder of the manuscript is dedicated to current scaffold fabrication methods, their unique capabilities and perceived shortcomings. The range of biomaterials employed in each fabrication method is summarized. Selected traditional and non-traditional fabrication methods are discussed with a highlight on their future potential from the authors' perspective. This study is motivated by the rapidly growing demand for effective scaffold fabrication processes capable of economically producing constructs with intricate and precisely controlled internal and external architectures. STATEMENT OF SIGNIFICANCE: The manuscript summarizes the current state of fabrication technologies and materials used for creating scaffolds in bone tissue engineering applications. A comprehensive analysis of different fabrication methods (traditional and free-form) were summarized in this review paper, with emphasis on recent developments in the field. The fabrication techniques suitable for creating scaffolds for tissue engineering was particularly targeted and their use in bone tissue engineering were articulated. Along with the fabrication techniques, we emphasized the choice of materials in these processes. Considering the limitations of each process, we highlighted the materials and the material properties critical in that particular process and provided a brief rational for the choice of the materials. The functional performance for bone tissue engineering are summarized for different fabrication processes and the choice of biomaterials. Finally, we provide a perspective on the future of the field, highlighting the knowledge gaps and promising avenues in pursuit of effective scaffolds for bone tissue engineering. This extensive review of the field will provide research community with a reference source for current approaches to scaffold preparation. We hope to encourage the researchers to generate next generation biomaterials to be used in these fabrication processes. By providing both advantages and disadvantage of each fabrication method in detail, new fabrication techniques might be devised that will overcome the limitations of the current approaches. These studies should facilitate the efforts of researchers interested in generating ideal scaffolds, and should have applications beyond the repair of bone tissue.