One of the most intriguing protein materials found in nature is bone, a material composed of assemblies of tropocollagen molecules and tiny hydroxyapatite mineral crystals that form an extremely tough, yet lightweight, adaptive and multifunctional material. Bone has evolved to provide structural support to organisms, and therefore its mechanical properties are of great physiological relevance. In this article, we review the structure and properties of bone, focusing on mechanical deformation and fracture behavior from the perspective of the multidimensional hierarchical nature of its structure. In fact, bone derives its resistance to fracture with a multitude of deformation and toughening mechanisms at many size scales ranging from the nanoscale structure of its protein molecules to the macroscopic physiological scale.

On the Mechanistic Origins of Toughness in Bone

Recent approaches towards bone tissue engineering

Recent approaches towards bone tissue engineering.

The significance of crack-resistance curves to the mixed-mode fracture toughness of human cortical bone Elizabeth A. Zimmermann a,b , Maximilien E. Launey a and Robert O. Ritchie a,b  a b Materials Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 Department of Materials Science and Engineering, University of California, Berkeley, CA 94720 ABSTRACT The majority of fracture mechanics studies on the toughness of bone have been performed under tensile loading. However, it has recently been shown that the toughness of human cortical bone in the transverse (breaking) orientation is actually much lower in shear (mode II) than in tension (mode I); a fact that is physiologically relevant as in vivo bone is invariably loaded multiaxially. Since bone is a material that derives its fracture resistance primarily during crack growth through extrinsic toughening mechanisms, such as crack deflection and bridging, evaluation of its toughness is best achieved through measurements of the crack-resistance or R-curve, which describes the fracture toughness as a function of crack extension. Accordingly, in this study, we attempt to measure for the first time the R-curve fracture toughness of human cortical bone under physiologically relevant mixed-mode loading conditions. We show that the resulting mixed-mode (mode I + II) toughness depends strongly on the crack trajectory and is the result of the competition between the paths of maximum mechanical driving force and ‚weakest‛ microstructural resistance. Keywords: Human cortical bone; mixed-mode fracture; fracture toughness; crack-growth resistance curve Corresponding author. tel: +1 (510) 486-5798; fax: +1 (510) 643-5792. E-mail address: roritchie@lbl.gov (R.O. Ritchie).

The significance of crack-resistance curves to the mixed-mode fracture toughness of human cortical bone

Among different treatments of critical-sized bone defects, bone tissue engineering (BTE) is a fast-developing strategy centering around the fabrication of scaffolds that can stimulate tissue regeneration and provide mechanical support at the same time. This area has seen an extensive application of bioceramics, such as calcium phosphate, for their bioactivity and resemblance to the composition of natural bones. Moreover, recent advances in additive manufacturing (AM) have unleashed enormous potential in the fabrication of BTE scaffolds with tailored porous structures as well as desired biological and mechanical properties. Robocasting is an AM technique that has been widely applied to fabricate calcium phosphate scaffolds, but most of these scaffolds do not meet the mechanical requirements for load-bearing BTE scaffolds. In light of this challenge, various approaches have been utilized to mechanically strengthen the scaffolds. In this review, the current state of knowledge and existing research on robocasting of calcium phosphate scaffolds are presented. Applying the Gibson-Ashby model, this review provides a meta-analysis from the published literature of the compressive strength of robocast calcium phosphate scaffolds. Furthermore, this review evaluates different approaches to the mechanical strengthening of robocast calcium phosphate scaffolds. The aim of this review is to provide insightful data and analysis for future research on mechanical strengthening of robocast calcium phosphate scaffolds and ultimately for their clinical applications. 

http://manuscript.elsevier.com/S0928493121007189/pdf/S0928493121007189.pdf

Toward stronger robocast calcium phosphate scaffolds for bone tissue engineering: A mini-review and meta-analysis

To respond to the increasing need for bone repair strategies, various types of biomaterials have been developed. Among those, calcium phosphate (CaP) ceramics are promising since they possess a chemical composition similar to that of bones. To be suitable for implants, CaP ceramics need to fulfill a number of biological and mechanical requirements. Fatigue resistance and toughness are two key mechanical properties that are still challenging to obtain in CaP ceramics. This paper thus reviews and discusses current progress in the processing of CaP ceramics with bioinspired microstructures for load-bearing applications. First, methods to obtain CaP ceramics with bioinspired structure at individual lengthscales, namely nano-, micro-, and macroscale are discussed. Then, approaches to attain synergistic contribution of all lengthscales through complex and biomimetic hierarchical structures are reviewed. The processing methods and their design capabilities are presented and the mechanical properties of the materials they can produce are analyzed. Their limitations and challenges are finally discussed to suggest new directions for the fabrication of biomimetic bone implants with satisfactory properties. The paper could help biomedical researchers, materials scientists and engineers join forces to create the next generation of bone implants.

Bioinspired approaches to toughen calcium phosphate-based ceramics for bone repair.

Natural materials such as bone and enamel have intricate microstructures with inorganic minerals oriented to perform multiple mechanical and biological functions. Current additive manufacturing methods for biominerals from the calcium phosphate (CaP) family enable fabrication of custom-shaped bioactive scaffolds with controlled pore structures for patient-specific bone repair. Yet, these scaffolds do not feature intricate microstructures similar to those found in natural materials. In this work, we used direct material extrusion to 3D print water-based inks containing CaP microplatelets, and obtained microstructured scaffolds with various designs. To be shear-thinning and printable, the ink incorporated a concentration of 21 – 24 vol% CaP microplatelets of high aspect ratio. Good shape retention, print fidelity and overhanging layers were achieved by simultaneous printing and drying. Combined with the 3D design, versatile CaP microstructured objects can be built, from porous scaffolds to bulk parts. Extruded filaments featured a core-shell microstructure with graded microplatelet orientations, which was not affected by the printing parameters and the print design. A simple model is proposed to predict the core-shell microstructure according to the ink rheology. Given the remaining open porosity after calcination, microstructured scaffolds could be infiltrated with an organic phase in future to yield CaP biocomposites for hard tissue engineering.

Peifang Dee

Papers

Bioinspired approaches to toughen calcium phosphate-based ceramics for bone repair.

Fabrication of Microstructured Calcium Phosphate Ceramics Scaffolds by Material Extrusion-Based 3D Printing Approach

Fabrication and Testing of Bioinspired Composites with Curved Multilayer Microstructures