Materials that have been used in bone-tissue engineering include polymers and biocomposites. A description of these materials is given below.
1.4.1 Biodegradable polymers
As a consequence of the advantage of biodegradability that biodegradable polymers offer, they have found increasing use in medical devices (Middleton and Tipton, 2000). Some
commercially available biodegradable medical devices include SmartPins (used for fracture fixation), LactoSorb Screws and Plates (used for craniomaxillofacial fixation), Meniscus Arrow (used for meniscus repair) and Meniscal Stinger (used for meniscus repair) (Middleton and Tipton, 2000). All these devices are polyesters composed of homopolymers or copolymers of glycolide and lactide. Additionally, biodegradable polymers have been widely researched for tissue engineering purposes due to their biocompatibility and the ease with which they can be processed into complex shapes (Thomson et al., 1995; Maquet and Jerome, 1997; Middleton and Tipton, 2000). Biodegradable polymers can be divided into two categories – natural and synthetic.
1.4.1.1 Natural biodegradable polymers
Natural biodegradable polymers were the first to be used as scaffolds for tissue regeneration (Thomson et al., 1995; Gomes and Reis, 2004). Collagen has been used to repair nerve, skin, cartilage and bone while chitosan has been shown to exhibit biostimulating activities in the healing process of various tissues (Maquet and Jerome, 1997;
Gomes and Reis, 2004). Natural polymers have the advantage of possessing a highly organized structure at both molecular and macroscopic levels, and exhibiting desirable properties as biomaterials, such as the ability to induce tissue ingrowth. However, natural polymers also have three main disadvantages: (i) antigenicity, this usually leads to adverse tissue reaction and immune rejection; (ii) patient to patient variation in degradation rate due to the fact that the degradation rate of natural polymers is usually reliant on enzymatic processes; and (iii) poor mechanical performance (Maquet and Jerome, 1997; Thomson et al., 1995; Gomes and Reis, 2004). Other natural biodegradable polymers that have been investigated for tissue engineering include, but are not limited to, gelatin (Swetha et al.,
2010; Sisson et al., 2010; Liu et al., 2009; Malafaya et al., 2007), cellulose (Tsioptsias and Panayiotou, 2008; Fang et al., 2009; Zaborowska et al., 2010), alginate (Fan et al., 2005;
Malafaya et al., 2007; Drury and Mooney, 2003; Li et al., 2005b; Turco et al., 2009) and hyaluronic acid (Drury and Mooney, 2003; Lee and Mooney, 2001; Kim et al., 2008b).
1.4.1.2 Synthetic biodegradable polymers
Synthetic biodegradable polymers offer greater advantages and versatility over natural polymers because their molecular weight and molecular weight distribution (with varying degrees of accuracy depending on, among other factors, the type of polymerization reaction) can be easily tuned to give a wider range of properties (Gomes and Reis, 2004;
Maquet and Jerome, 1997; Thomson et al., 1995; Middleton and Tipton, 2000). These characteristics greatly affect the physico-mechanical properties (such as strength and degradation rate) of the polymer (Maquet and Jerome, 1997; Thomson et al., 1995; Gomes and Reis, 2004). These polymers usually degrade by simple chemical hydrolysis because they are synthesised to have hydrolytically unstable linkages in their backbone (Thomson et al., 1995; Maquet and Jerome, 1997; Middleton and Tipton, 2000). As a result, the degradation rate does not vary from patient to patient (unless there are local pH variations due to inflammation, implant degradation etc) (Gomes and Reis, 2004). A further advantage of synthetic polymers is their easy processibility into porous materials. Copolymerization can be used to alter degradation rates and also impart degradability on a hydrolytically stable polymer (Thomson et al., 1995).
There are different types of synthetic polymers used as tissue engineering scaffolds, these include linear aliphatic polyesters [this class of polymers includes poly(glycolic acid) - PGA, poly(lactic acid) - PLA, poly(lactic-co-glycolic acid) - PLGA, and poly(ε-caprolactone) - PCL],
poly(dioxanone), polyethylene oxide, polybutylene terephthalate, poly(propylene fumarate), and poly(amino acids) (Ma, 2004; Gomes and Reis, 2004). Poly(α-hydroxyl acids) especially poly(glycolic acid) and poly(lactic acid) are the most widely investigated and most commonly used synthetic biodegradable polymers in medicine (Gomes and Reis, 2004;
Pachence et al., 2007; Gupta et al., 2007; Middleton and Tipton, 2000) based in part on their biocompatibility and their approval by the FDA for human clinical use (Thomson et al., 1995).
1.4.2 Biocomposites
Bone is a composite consisting of an organic phase and a mineral phase (Hench, 2005;
Piekarsk, 1973; Yamashita et al., 2002; Rho et al., 1998; Wei and Ma, 2004; Venugopal et al., 2010) as mentioned in Section 1.3. In an effort to closely mimic the composite nature of bone, polymer/calcium phosphate biocomposites have been widely researched using various fabrication techniques (Wei and Ma, 2004; Zhang et al., 2007c; Venugopal et al., 2008c; Venugopal et al., 2010; Ngiam et al., 2009; Zhang and Ma, 1999b; Prabhakaran et al., 2009; Supova, 2009; Kim et al., 2006a; Sui et al., 2007; Kim et al., 2005; Jagur-Grodzinski, 2006). Synthetic biodegradable polymers can be easily processed into porous 3-dimensional (3D) tissue engineering scaffolds, however, their surfaces do not enhance cell adhesion, differentiation and proliferation (Venugopal et al., 2008c; Venugopal et al., 2010). On the contrary, calcium phosphates such as hydroxyapatite and β-TCP have been shown to be osteoconductive (Rezwan et al., 2006). As a result, synthetic biodegradable polymer/calcium phosphate biocomposite scaffolds have been investigated as an improvement on synthetic biodegradable polymer scaffolds. For instance, when cultured with cells, a poly(L-lactic) acid (PLLA)/HA composite scaffold showed new tissue formation throughout the scaffold while
new tissue formation was only observed on the surface layer (<240 µm) of poly(DL-lactic-co-glycolic acid) (PLGA) foams (Wei and Ma, 2004). Similarly, Venugopal et al. (2008) observed higher mineral deposition on collagen/HA composite scaffolds when cultured with osteoblasts than on pure collagen scaffolds (Venugopal et al., 2008b).
It has also been suggested, that polymer/calcium phosphate biocomposite scaffolds exhibit improved degradation properties, for instance, by monitoring the pH variations during incubation in phosphate buffered saline (PBS) for 24 weeks, it was found that the pH value of PLLA-HA composite scaffold was more stable than that of pure PLLA scaffold and pure HA scaffold (Zhang and Ma, 1999b).