**2.2.4 Polycaprolactone (PCL)**

228 Biomedical Science, Engineering and Technology

PGA loses its strength in 1 to 2 months when hydrolyzed and its mass within 6 to 12 months (Nair & Laurencin, 2007). When inserted in the body, PGA breaks down into glycolic acid. Glycolic acid is not toxic and can be excreted in the urine or converted into H2O and CO2 and subsequently removed from the body via the respiratory system (Maurus & Kaeding, 2004). Despite the above-mentioned non-toxicity of glycolic acid, it may result in an increased and localized acid concentration leading to tissue dammage (Gunatillake & Adhikari, 2003, Taylor et al., 1994). This presents in particular problems for orthopaedic applications where implants with substantial dimensions are needed (Gunatillake & Adhikari, 2003). Together with the high degradation rate and low solubility, these acidic degradation products have hampered

The monomer building block of polylactic acid, lactic acid, is formed by converting sugar or starch from vegetable origin (e.g. wheat, corn, rice, etc.) via either bacterial fermentation or via a petrochemical process (Rasal et al., 2010). If PLA is implanted, it hydrolyses to its building block lactic acid which is a normal human metabolic by-product (Gunatillake & Adhikari, 2003). Lactic acid is degraded into H2O and CO2 which can be further removed by the respiratory system (Nair & Laurencin, 2007, Maurus & Kaeding, 2004). As can be seen in Table 1, lactic acid is a chiral molecule and therefore different forms of PLA occur. The two most important forms are poly(L-lactic acid) (PLLA) and poly(DL-lactic acid) (PDLLA). Similar to PGA, PLLA has a high degree of crystallinity (± 37% depending on molecular weight and production processes) (Nair & Laurencin, 2007). Compared to PGA, PLLA slowly degrades: when PLLA is hydrolyzed, it loses its strength in circa 6 months. However, no mass loss is observed for a very long time and total degradation amount up to several years (Middleton & Tipton, 2000, Nair & Laurencin, 2007, Bergsma et al., 1995). Next to this slow degradation, PLLA offers good tensile strength, a high tensile modulus and low extension and can therefore be applied in load bearing applications like in orthopaedic fixation devices (Nair & Laurencin, 2007). PLLA fibres are also often used as surgical sutures, while PLLA composites, porous membranes or sponges can be employed as scaffolding matrices for tissue regeneration (Hu & Huang, 2010, Heino et al., 1996, Lam et al., 1995, Vaquette et al., 2008, Ma et al., 2006, Chen & Ma, 2004). For some other

applications, the long degradation time of PLLA however presents a major concern.

PDLLA has an amorphous nature resulting in a substantial lower strength compared to PLLA (Nair & Laurencin, 2007). Moreover, PDLLA loses its strength in 1 to 2 months and its mass within 12 to 16 months (Maurus & Kaeding, 2004). Taking into account this low strength and its fast degradation rate, PDLLA can be employed as drug delivery system or as low strength scaffolding matrix for tissue engineering (Nair & Laurencin, 2007, Xie & Buschle-Diller, 2010).

A lot of research has been carried out on the development of a full range of poly(lactic-coglycolic acid) (PLGA) polymers. This research has indicated that the degradation rate of PLGA strongly depends on the lactic acid/glycolic acid ratio (Gilding & Reed, 1979, Reed & Gilding, 1981, Miller et al., 1977). It is common knowledge that the intermediate co-polymers are much more unstable than the homo-polymers: a 50/50 PLGA and an 85/15 PLGA degrade in 1-2 months and 5-6 months respectively (Middleton & Tipton, 2000). This opportunity to tune the degradation rate of the polymer by varying the monomer ratio has made PLGA an ideal

the use of PGA for biomedical engineering applications.

**2.2.3 Poly(lactic-co-glycolic acid) (PLGA)** 

**2.2.2 Polylactic acid (PLA)** 

Polycaprolactone (PCL) is of great interest since it can be obtained from the relatively cheap monomer unit ε-caprolactone (Storey & Taylor, 1998). PCL degrades very slowly and complete degradation can take several years. Due to this slow degradation, its non-toxicity and its high permeability to small drug molecules, PCL has in the beginning been studied as a polymer for long-term drug delivery systems. PCL also offers excellent biocompatibility. Therefore, recently extensive research has been done on the use of PCL as scaffold matrices in tissue regeneration (Chiari et al., 2006, Mondrinos et al., 2006). Also several co-polymers have been developed to increase the degradation rate compared to pure PCL (Li et al., 2002, Li et al., 2003, Qian et al., 2000, Wang et al., 2001). For co-polymers synthesized from Llactide and ε-caprolactone, the degradation rate was again strongly influenced by the Llactide/ε-caprolactone ratio.

### **2.2.5 Polyhydroxyalkanoates (PHA)**

Polyhydroxyalkanoates (PHA) are structurally related to PLA and are a polyester class derived from hydroxyalkanoic acids which can vary in chain length and in the hydroxyl group positions (Breulmann et al., 2009). As is the case for PLA, PHA can be obtained from renewable resources like starch, sugars or fatty acids, however, chemical transformation is not needed. The most widespread PHA is poly-3-hydroxybutyrate (PHB) which was discovered in 1920 as produced by the bacteria "Bacillus megaterium" (Nair & Laurencin, 2007). Subsequent research showed that PHB could also be synthesized via other bacterial strains and via chemical routes. **Subsequent research showed that PHB could also be synthesized via other bacterial strains and via chemical routes** (Shelton et al., 1971).

PHB degrades into D-3-hydroxybutyrate which is a normal element of human blood (Wang et al., 2001). To be used directly as biopolymer, PHB has the disadvantage of a very low degradation rate in the body compared with other biodegradable polyesters and is often considered too brittle for many applications (Nair & Laurencin, 2007, Pompe et al., 2007). Therefore, co-polymers of 3-hydroxybutyrate with other monomers such as 3-hydroxyvalerate have been synthesized (Nair & Laurencin, 2007). This poly(3-hydroxybutyrate-co-3 hydroxyvalerate) (PHBV) is far less brittle and thus offers more potential as biomaterial (Nair & Laurencin, 2007, Ojumu et al., 2004). Moreover, PHBV is piezoelectric which enables electrical stimulation – known for promoting bone healing – of the implant (Nair & Laurencin, 2007). Although the faster degradation rate of PHBV compared to PHB, it has been observed that the in vivo degradation of both polymers remains slow. Therefore, these polymers may be potential candidates for long term implants.

### **2.2.6 Polybutylene succinate (PBS)**

Polybutylene succinate (PBS) was discovered in 1990 and commercialized under the trade name Bionolle® (Fujimaki, 1998). PBS degrades via naturally occurring enzymes and microorganisms into H2O and CO2 (Tserki et al., 2006). PBS can be easily produced in a wide variety of forms and structures, such as yarns, non-wovens, films, mono-filaments and it offers excellent mechanical properties comparable with polyethylene or polypropylene (Li et al., 2005, Vroman & Tighzert, 2009). These characteristics makes PBS an excellent choice for use as scaffolds in tissue regeneration.
