Abstract
This chapter presents an overview related to the modern approach of hydroxyapatite (HA) based composite for biomedical applications. Composite refers to a heterogeneous combination made up of two or more materials having different composition, properties and morphology in order to produce new materials with specific physical, chemical and mechanical characteristics (Salernitano and Migliaresi 2003). Simply speaking, the composite contains at least two or more components known as matrix and reinforcement. Biocomposites, on the other hand, refers to the blends of different materials based on their biocompatibility for various applications. Different types of composites, already in use or currently investigated for various biomedical applications, are presented in this chapter. The focus will be on the types of HA based composite, synthesis and fabrication approaches, characterization, various biomedical applications, the cell-material interactions and its bioactivity and biocompatibility. HA based composite also known as bioceramics composite and been used for the past several years for various biomedical applications and recently its being used mainly in tissue engineering. Calcium phosphate or single-phase HA based composite have been widely used for the past thirty years. The advantages offer by the HA based composites consist of high compressive strength, comparative inertness towards body fluids, its attractive appearance, biodegradability, and high biocompatibility led to the use of bioceramics composite in dental and orthopaedic related biomedical applications. The structure of this chapter is organized as follows. In Sect. 13.2, classifications of the HA based composite materials are described. This is followed by a description of the modern synthesis or fabrication and characterization approaches (Sects. 13.3 and 13.4). Section 13.5 deals with current applications of HA based composite in biomedical focusing on the ideal properties and cell-material interaction. Concluding remarks are offered in the last Sect. 13.6.
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1 Introduction
This chapter presents an overview related to the modern approach of hydroxyapatite (HA) based composite for biomedical applications. Composite refers to a heterogeneous combination made up of two or more materials having different composition, properties and morphology in order to produce new materials with specific physical, chemical and mechanical characteristics (Salernitano and Migliaresi 2003). Simply speaking, the composite contains at least two or more components known as matrix and reinforcement. Biocomposites, on the other hand, refers to the blends of different materials based on their biocompatibility for various applications. Different types of composites, already in use or currently investigated for various biomedical applications, are presented in this chapter. The focus will be on the types of HA based composite, synthesis and fabrication approaches, characterization, various biomedical applications, the cell-material interactions and its bioactivity and biocompatibility. HA based composite also known as bioceramics composite and been used for the past several years for various biomedical applications and recently its being used mainly in tissue engineering. Calcium phosphate or single-phase HA based composite have been widely used for the past thirty years. The advantages offer by the HA based composites consist of high compressive strength, comparative inertness towards body fluids, its attractive appearance, biodegradability, and high biocompatibility led to the use of bioceramics composite in dental and orthopaedic related biomedical applications. The structure of this chapter is organized as follows. In Sect. 13.2, classifications of the HA based composite materials are described. This is followed by a description of the modern synthesis or fabrication and characterization approaches (Sects. 13.3 and 13.4). Section 13.5 deals with current applications of HA based composite in biomedical focusing on the ideal properties and cell-material interaction. Concluding remarks are offered in the last Sect. 13.6.
2 Classification of Hydroxyapatite (HA) Based Composites
HA based composite used mainly in biomedical applications can be classified into various classifications. Herein, the main four classification consist of metal/metal oxide matrix HA based composite, polymer matrix HA based composite, carbonaceous HA based composite, and the hybrid HA based composite (Fig. 13.1). In terms of polymer matrix, HA based composite can be further divided into natural and synthetic polymer.
2.1 Metal Matrix Hydroxyapatite (HA) Based Composite
HA having component comparable to crystal structure of bone offers both bioactivity and compatibility. The major bottleneck related to the application of HA mainly due to their low fracture toughness and flexural strength. In order to enhance the mechanical properties of HA, metal and metal oxide such as magnesium, titanium dioxide, zirconia, alumina, and iron oxide usually incorporated in order to reinforce the prepared HA-based composites. The metal matrix HA based composite possess good tensile strength, high Young’s modulus, high strength and highly resistance to corrosion. For biomedical application, the HA composite should be biodegradable and non-toxic (Bommala et al. 2018). Table 13.1 listed several types of metal and metal oxide previously used in preparing HA based composite for various biomedical application.
2.2 Polymer Matrix Hydroxyapatite (HA) Based Composite
Reinforcement can be achieved by incorporating HA with either natural or synthetic polymer the prepared HA-based composites (Fig. 13.2). Polymers provide various properties as a matrix for bone tissue engineering applications. Natural polymer-based composites received more attention than synthetic polymer composites owing to the biocompatible and biodegradable properties offered by natural polymers. Other advantages included biological recognition, good attachment to cells and having the ability to be degraded and resorbed by the body (Venugopal et al. 2010). Chitosan, chitin, collagen, gelatin and polylactic acid (PLA), hylauronic acid derivatives, starch, fibrin gels, silk and lignocelluloses are among popular natural polymer in preparing composites for medical application.
Apart from biocompatible and biodegradable, antimicrobial and antioxidant properties of the prepared HA based composites widely expand their application in various fields ranging from food nutrition, biomedical engineering up to pharmaceutical. The composites also should mimic the behavior of the replaced tissue, providing an ideal when in contact with the tissue and capable to be degraded progressive as soon as the regeneration process ended. However, these naturally derived polymers have several drawbacks such as instability and immunogenicity from batch to batch. So, synthetic polymers with modifiable properties such as polyvinyl alcohol (PVA), polyurethane (PU), poly-d, l-lactic acid (PDLLA), polyethylene glycol (PEG), polydimethylsiloxane (PDMS), polyether ether ketone (PEEK) and thermoplastic polyvinylidene difluoride (PVDF) are among synthetic polymers usually used to create HA based composite as they offer exceptional applicability. The advantages offered by synthetic polymer consist of controlled mechanical properties, biodegradable, and reproducible for an extensive production.
2.3 Carbonaceous Hydroxyapatite (HA) Based Composite
Along with the excitement of nanoscience and the diverse applications of carbon-based nanomaterials, researchers worldwide started to utilise different carbonaceous materials to prepare nanocomposites either as a matrix material or as an additional reinforcing material. The carbonaceous materials reported to be bioactive for one or more purposes as it offers high competency for bone tissue engineering equipped with biocompatibility with native tissues and antibacterial activity. The incorporation of various carbonaceous materials with HA led to high biocompatibility and excellent structural properties of the prepared nanocomposite. The use of carbonaceous material such as glassy or pyrolytic carbon, fullerenes, carbon nanotubes (CNTs) graphene oxide (GO), carbon dots (CDs) and their derivatives and compositions are unique and innovative trend in creating HA based composites (see Fig. 13.3).
2.4 Hybrid Hydroxyapatite (HA) Based Composite
A major challenge in tissue engineering is the development of composite materials capable of promoting the desired cells and tissue behavior (Davis and Leach 2008). So, hybrid HA based composite biomaterials having the capability to synergize the beneficial properties of multiple materials into an outstanding matrix (Bencherif et al. 2013). The hybrid HA prepared by combination of various other materials such as metal or metal oxides with either natural or synthetic polymers or carbonaceous materials. The hybrid composites offer tuneable properties and providing enhancement in cellular and tissue interaction tissue. There are numerous hybrid HA based composite materials (as listed in Fig. 13.4) in order to promote the formation of cell proliferation for tissue engineering applications.
3 Modern Synthesis and Fabrication Approaches
Owing to the importance of HA based composites in various biomedical applications not limited to tissue regeneration and drug delivery applications. So, various techniques (see Fig. 13.5) have been reported for the preparation of HA based composites (Haider et al. 2017). Two important factors when choosing the synthesis approach are particle size and morphology of the final product of HA. To date, many findings correlated the HA synthesis techniques with the particle size, but very few articles reported the fabrication method and the morphology control of HA based composites.
The commonly used techniques for the preparation of HA based composite including biometrics, freeze thawing, electronspinning, electrospraying, chemical precipitation, hydrothermal, solid state synthesis at high temperatures, microwave irradiation, surfactant-assisted precipitation, wet chemical synthesis, powder metallurgy, ultrasound cavitation, solvent casting, sol-gel method and green synthesis approach. Chemical precipitation, hydrothermal and sol–gel technique listed as the most frequently approach in the HA based nanocomposite fabrications. Table 13.2 summarized several common methods and the developed HA based composites. Until now researchers still are investigating for the method to prepare composites of HA with the right stoichiometry and having both high crystallinity and aspect ratio. So far, only conventional wet mechano-chemical methods have been reported to have the ability to control the stoichiometry of the final product.
4 Characterization of HA Based Composites
Various characterization techniques have been used to characterize HA based composites. The characterization techniques can be divided into spectroscopic and direct visualization as listed in the Fig. 13.6. Table 13.3 concluded main findings of various HA based composites using both characterization techniques.
5 Current Application of Hydroxyapatite (HA) Based Composites
Hydroxyapatite based composites have various biomedical applications especially in tissue engineering. Tissue engineering or regenerative medicine is a field that involves in promoting new tissues or organs to restore defect, lost or damaged tissues and organs by engineered products. The current practice of using bone grafts for treating patients with bone defect resulted from trauma, pathology and congenital disease brings together a few disadvantages. The advancement of tissue engineering has shed a new light for both clinicians and patients involved. The triad of tissue engineering requires stem cells, growth factors and scaffold-based composites. HA based composite is one of the preferred scaffolds due to its similar composition and structure with the natural human bone (Roffi et al. 2017).
5.1 Bone Regeneration
Bone disorders due to trauma, congenital deformity and malignancy are one of the pathological areas that require transplantation of bone graft. Bone graft can either be autograft, allograft, xenograft or bone substitutes. However, each graft possesses different drawbacks that hinder optimal outcome after the surgery. Since the last few decades, the advancement in regenerative medicine has gradually being investigated to overcome the limitation of usual practice, including the bone tissue regeneration area. Even though it is difficult to mimic nature, recent scientific and technological findings show promising results to provide an alternative option to the current management. Scaffold, one of the important components in tissue engineering has received tremendous attention among researchers. The search for the right scaffold in bone tissue engineering since past few decades is still ongoing. The ideal scaffold for bone regeneration should have the following properties: biocompatible, bioresorbable, osteoconductive, osteoinductive and structurally similar to the native bone.
5.2 Ideal Properties of Scaffolds
Bioceramic such as HA, bioactive glass, zirconia and β-tricalcium phosphate (β-TCP) are mostly used for hard tissue regeneration (Huang et al., 2018; Lukić et al., 2011). HA based scaffolds have been reported to have good biocompatibility and osteoconductivity; suitable for bone regeneration (Hao et al., 2017). Owing to similar chemical composition with native bones HA has become the most common bioceramic used in bone tissue engineering (Mondal et al. 2019; Yang et al. 2019). Scaffolds chosen should mimic the actual microenvironment to allow cells to interact and behave at the optimum condition. Hence, scaffolds properties are essential in determining cellular response and fate (Loh and Choong 2013). There are few requirements for ideal scaffolds required in bone regeneration that include physical properties, biomaterial properties and mechanical properties (Tables 13.4 and 13.5).
Mechanical property of ideal scaffold in bone regeneration requires sufficient mechanical strength in order to maintain the cell integrity until formation of new bone. Newly bone regeneration should withstand loading to prevent shielding as compared to the surrounding native bone (Loh and Choong 2013).
6 Conclusion and Future Remarks
This chapter reviewed modern approach used in the fabrication of HA based composite for various biomedical applications. Wide range of methods available for fabricating HA based composites have developed in the past few decades. Each of the fabrication methods has its own benefits and drawbacks. Factors need to be taken into consideration include the overall cost, easy and reliable procedures, the performance and characteristic of the end product. The HA composites prepared with either polymers, metals and metal oxide, carbonaceous and the hybrid mixtures have gain worldwide attention due to the outstanding biological properties on top of chemical resemblance to the bone tissues. It is important to consider the ideal properties of the biomaterial in designing the suitable HA based composite for biomedical applications. Future work will focus on the advancement and improvement in fabrication real bone like HA composites with improved mechanical, bioactivity, biocompatibility and osteoconductivity. The cell-material interaction, in vitro and in vivo studies will be the focus in the future.
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Abdullah, C.A.C., Esa, E.F., Yazid, F. (2020). Modern Approach of Hydroxyapatite Based Composite for Biomedical Applications. In: Siddiquee, S., Gan Jet Hong, M., Mizanur Rahman, M. (eds) Composite Materials: Applications in Engineering, Biomedicine and Food Science. Springer, Cham. https://doi.org/10.1007/978-3-030-45489-0_13
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