The World Scientific Encyclopedia of Nanomedicine and Bioengineering II

The following sections are included:

• Contents
• Preface
• List of Contributors

Since various interactions among cells, surrounding tissues and implanted biomaterials always occur at their interfaces, the surface properties of potential implants appear to be of paramount importance for their clinical success. In view of the fact that a limited amount of materials appear to be tolerated by living organisms, a special discipline called surface engineering was developed to initiate the desirable changes to the exterior properties of various materials but still maintaining their useful bulk performances. In 1975, this approach resulted in introducing a special class of artificial bone grafts, composed of various mechanically stable (consequently, suitable for load bearing applications) implantable biomaterials and/or bio-devices covered by calcium orthophosphates (CaPO₄) to both improve biocompatibility and provide an adequate bonding to the adjacent bones. Over 5,000 publications on this topic have been published since then. Therefore, a thorough analysis of the available literature has been performed and about 50 (this number is doubled, if all possible modifications are counted) deposition techniques of CaPO₄ have been revealed, systematized and described. These CaPO₄ deposits (coatings, films and layers) used to improve the surface properties of various types of artificial implants are the topic of this chapter.

When illness or trauma results in bone non-union that surpasses the self-regenerative capacity of tissue, a substitute material is needed to fill the void and favorably induce bone regeneration. Synthetically produced biomaterials with better reproducibility and availability are clinically needed as an alternative to human- and animal-derived scaffolds. Such materials often comprise some form of calcium phosphate (CaP) owing to their resemblance to bone-minerals. Of special interest is the development of new formation strategies with the aim of forming materials that to a high extent mimics that of the bone tissue it restores. Such strategies often include some level of biomimetics where naturally occurring processes are used as inspiration. In this review, the current state-of-the-art in biomimetic formation techniques using molecular self-assembly and biomimetic mineralization with the effort of forming hierarchical CaP bone-like structures are summarized. It is focused on, but not limited to, the use of amphiphiles as structure-directing agents to achieve control over the CaP mineralization process, i.e. CaP morphogenesis, polymorphism as well as the orientation and organization of CaP crystallites in hybrids. In conclusion, some preclinical data are presented, which clearly demonstrate the positive outlook for bone-like synthetic biomaterials formed using molecular self-assembly techniques.

Ions, including trace elements, have shown different positive biological effects on human body, especially on bone. This chapter is not intended to be a comprehensive review, but an attempt to highlight knowledge of ions useful in calcium phosphates with specific biological effects.

Bioactive glass (BG) has been gaining much attention as a promising bone repairing material due to its good osteoconductivity and osteoproductivity. The development of BG has mainly been of three types: melt-derived BG, sol-gel derived BG and micro/nano-bioactive glass (MNBG). The chapter focuses on the recent progress about BG and corresponding BG-based scaffolds. The compositions, structures and properties of BG are reviewed, including the mechanism of bioactivity, bone bonding ability and gene activation. Then, examples of the preparation and properties of MNBG with controlled morphologies, structure and particle size are presented, obtained by using sol-gel method combined with template self-assembly. The surface micro/nano structure and micro/nano size of MNBG effectively enhanced the in vitro apatite-forming bioactivity, cellular attachment, proliferation, differentiation and osteogenic gene expressions compared with the melt-derived BG and sol-gel derived BG. Additionally, some representative BG scaffolds such as melt-derived and sol-gel derived BG scaffolds and BG composites scaffolds are introduced, including the preparation method, pore structure and relevant properties of various BG scaffolds.

For load-bearing applications, orthopaedic implants are generally made of bioinert metals with appropriate mechanical properties and modified surfaces (i.e. roughened, coated or a combination thereof), to enhance the surface biocompatibility and osteoconductivity. Coatings consisting of organic (extracellular matrix proteins, biological peptides, growth factors, etc.) or inorganic (calcium phosphate (CaP), calcium silicate, titanium, etc.) components impart bioactivity and biocompatibility to the metallic surface that promote bone ingrowth and differentiation of stem cells into osteoblasts leading to enhanced osteointegration of the implant. This chapter reviews the current and future use of biological coatings for orthopedic implants with the emphasis on the coating techniques, composition, structure, mechanical property and biological performance.

Osteoporosis involves a gradual deterioration of the bone mineral, and is characterized by low bone mass and microarchitectural deterioration of bone structure, resulting in bone fragility and an increase in susceptibility to fracture over several decades of life. The continued increase in the aged population has generated higher quantities of osteoporosis-related injuries. In many cases these symptoms are associated with pain and especially, the osteoporotic (micro-) trauma that cannot be readily repaired by self-heal approach has typically been treated using a variety of technology strategies. For instance, man-made devices have been developed to relieve pain, to restore function and to facilitate osteoporotic fracture healing. Existing biomedical implants typically consist of a single metal, ceramic or polymer or of a relatively coarse combination of two or three components. Although these materials provide solutions for many general defects, their bioactivity and dense structure are generally not satisfactory for guiding osteoporotic fracture healing and defect repair. Recent development in the fields of oral administration, local intervention, stem cell technology and minimally invasive therapy suggest that the nutrition and regenerative medicine approaches are possibly optimal strategies to target the treatment of such pathological issues. In this chapter, both experimental and clinical technologies for treatment of osteoporosis and osteoporosis-related injuries and their respective indications, techniques and results are described in relation with the application and limitations of biomaterials.

The demand for bioactive materials to repair or regenerate bone has being growing fast. Silicate-based bioactive materials have attracted much attention in the last 10 years due to their excellent biological response in vitro and in vivo. This chapter introduces the design methods for silicate-based bioglass and silicate-based ceramics materials. Strategies about structure design and composition design for these two types of materials and the enhanced properties of the designed materials have been introduced in detail.

Calcium phosphate cements (CPCs) can be used as injectable bone void fillers as well as a complement to fracture stabilization. They are biocompatible and may present a bioactivity that can permit their replacement by the host’s own tissue over time. Brushite CPCs are becoming increasingly studied due to a generally faster conversion rate to bone than what is possible with the more traditional apatite cements. Recent studies have also demonstrated the possibility of reaching strengths similar to those of apatite cements. This chapter provides an overview of the mechanical properties of brushite CPCs. The compressive strength is the most widely studied mechanical property, and ranges between approximately 1 and 74 MPa, depending on several factors such as cement composition, preparation, etc. There is a limited amount of data in the literature on the tensile, flexural, shear and elastic properties of the cements. The available studies report direct tensile strengths between 1 and 8 MPa, indirect tensile strengths between 1 and 10 MPa, flexural strengths between 1 and 13 MPa, a shear strength of approximately 3 MPa and a Young’s modulus ranging between 1 and 27 GPa. The fatigue properties of the cements are even more seldom studied, and more effort is needed in this area.

Design of bioactive materials for bone repairment and regeneration is of great importance in biomedical fields. Some bioactive materials such as hydroxyapatite, calcium silicate, calcium carbonate, bio-glass have been explored for the potential applications for bone repairment and regeneration. This chapter focuses on the recent development of cellulose and its composites in the potential applications for bone repairment and regeneration. Undoubtedly, cellulose is the most abundant natural linear polysaccharide polymer found on the earth, which has wide applications in biosorption, biofiltration and biocomposites. In this chapter, the cellulose composites especially cellulose/hydroxyapatite are reviewed via many typical examples. Our views have also been given on the future perspectives of cellulose and its nanocomposites in bone repairment and regeneration fields, which shows that there is a long way to go. It is expected that this chapter could contribute interesting contents to the topic of the book “Design of Bioactive Materials for Bone Regeneration” and provide opinion in the bioactive materials for bone repairment and regeneration.

Immobilization of bone anti-resorptive agents bisphosphonates in different inorganic, polymeric and nanocomposite scaffolds is advantageous for bone tissue engineering because of their action on osteoclasts, imparting bone adhesive properties to the scaffolds as well as the scaffolds bio-mineralization in vivo. These properties are also paramount in providing better fixation of orthopedic implants to bone. Chemical conjugation of bisphosphonates to imaging agents or drugs or polymer-based nano-carriers with physically encapsulated theranostics allows specific delivery of nanomedicines to bone which is important in diagnosis and therapy of bone diseases such as osteoarthritis, osteoporosis and bone cancer. These bone-targeting probes are also useful in monitoring of bone regeneration. Novel strategies emerged in which chemical attachment of bisphosphonate ligands to polymers may impart self-assembling properties to the polymers in the presence of Ca²⁺ and afford new physically assembled composite materials. Using bisphosphonate ligands attached to a carrier as affinity groups is another new modality of very well-known drugs which should be considered for the delivery of bone-inducing growth factors.

Suitable imaging methods, which span the macroscale to nanoscale, are essential to understanding endogenous bone regeneration, and bone repair in the presence of synthetic biomaterials. Coupling these imaging techniques with chemical analyses provides for both a qualitative and quantitative baseline for comparison of bone regeneration approaches. A multitude of characterization approaches exist based on light, electron, probe and X-ray techniques, for example. In this chapter, a selection of techniques most commonly employed in the investigation of bone regeneration will be introduced and their concepts briefly covered. Special emphasis will be placed on novel high-resolution 3D imaging methods involving electron microscopy.

The following section is included:

• Index