The demand of polymer scaffolds and load-bearing implants with good bioactivity and biocompatibility is ever increasing due to the large amount of ageing populations, and the number of patients suffering from bone disease, trauma, traffic accident and sports activity. In addition, bacteria and microorganisms often attach to the surfaces of medical implant materials and develop biofilms. Bacteria contamination of medical devices leads to infection risks with high morbidity and mortality. It also results in complications and implantation failures. These issues motivate chemists and materials scientists to develop novel biomaterials and devices with bactericidal properties.
Synthetic polymers have been widely employed as biomaterials for making medical devices and tissue engineering scaffolds since they exhibit attractive properties such as lightweight, good processability, mechanical flexibility and degradable behavior (certain biodegradable polymers). Degradable polymeric materials such as polylactic acid (PLA) and their blends are typically used for bone tissue engineering applications. Its disadvantages include low mechanical strength and inherent brittleness. By contrast, non-degradable polymer such as polyetheretherketone (PEEK) with high Young’s modulus, high temperature durability and excellent radiation stability has found clinical applications for fabricating trauma fixation devices and spinal cages. However, the elastic modulus of PEEK (3.8 GPa) is still far lower than that of human cortical bone.
Recent progress in nanotechnology research has led to the development and synthesis of novel nanomaterials with unique properties. Nanomaterials generally possess higher mechanical strength and biocompatibility compared to their micron-sized counterparts. Hydroxyapatite (HA) with a chemical composition of Ca10(PO4)6(OH)2 is an ideal material for bone replacements owing to its excellent biocompatibility, bioactivity and chemical similarity to the inorganic component of human bone tissues. However, HA is typically employed as a coating material for metallic bone implants and a filler material for polymer biocomposites due to its brittleness. For example, it generally requires high filler loading (i.e. 40 vol% HA) to polymer (polyethylene) for achieving biocompatibility. High filler content and large HA microparticles lead to poor processability and low mechanical strength of resulting biocomposites. Therefore, HA nanorod (nHA) with large surface area to volume ratio and at lower loading levels shows high potential for replacing HA microparticles for filler reinforcement in polymers. In this respect, nHA is employed as a nanofiller for non-degradable PEEK and degradable PLA for making nanocomposites for hard tissue replacement and soft tissue engineering applications.
Carbonaceous nanomaterials such as graphene and carbon nanotubes (MWNTs) exhibit exceptionally high elastic modulus of ~1TPa and excellent biocompatibility. Thus they can be used to reinforce polymers to form bionanocomposites for clinical applications. High purity graphene can be fabricated by means of chemical vapor deposition (CVD). At present, CVD-graphene is expensive and usually employed in the electronic and optoelectronic sectors for forming transparent conducting electrodes of solar cells and computer touch screen panels. To obtain graphene in large quantities, graphite flakes are reacted with strong oxidizing solutions to yield graphene oxide (GO), followed by either chemical or thermal reduction treatment to form reduced GO. Besides, the basal plane of GO carbon atoms consist of epoxide and hydroxyl groups, while its edge carbon atoms attach with carboxyl and carbonyl groups. Those functional groups can enhance interfacial bonding between the GO and polymeric matrix, leading to efficient stress transfer across the polymer-GO interface during mechanical testing. Thus GO sheets act as an effective nanofiller for polymers at low loading levels.
Metallic nanoparticles such as silver nanoparticles (AgNPs) and copper nanoparticles (CuNPs) are known to exhibit excellent antifungal and antimicrobial properties. In particular, AgNPs have received increasing attention of chemists and materials scientists for use as biocidal agents in clinical sectors. This is because they can be employed as nanofillers for polymers to form biocomposites with bactericidal activity. Those nanoparticles with large surface area often attach on the bacterial membrane. The inhibitory action of such metallic nanoparticle is associated with the release of metallic ions, leading to the membrane damage by inducing reactive oxygen species (ROS) inside bacterial cell.
PLA is a biodegradable polyester which finds wide applications in food packaging, wound dressing and scaffold. It generally degrade through hydrolysis of the ester groups. The low mechanical strength of PLA can be improved by adding nanofillers. As a result, 18 wt% nHA and 18 wt% nHA-x% Ag (x = 2, 6, 10, 18 and 25) are added to PLA for enhancing its mechanical strength, biocompatibility and bactericidal activity. Such nanocomposites have been prepared by melt-compounding process. The biocompatibility and an antibacterial behavior of such nanocomposites have been assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and disc diffusion techniques. The results show that all PLA/18% nHA-x% Ag have high bactericidal activity against E. coli and moderate activity against S. aureus. MTT results reveal that high AgNP contents (18 and 25 wt%) inhibit the proliferation of osteoblasts. However, composite hybrids with low loading Ag levels (2 and 6 wt%) show good biocompatibility over PLA.
In this thesis, electrospinning is employed to prepare porous nanofiller mats since the scaffolds exhibit highly connected porous network. PLA is selected as the polymeric matrix, whereas nHA-GO and GO-AgNPs hybrids are employed as the nanofillers. For the nHA-GO hybrid fillers, the results demonstrate that PLA mat reinforced with 15 wt% nHA and 1 wt% GO has the high tensile strength and modulus, as well as excellent cell proliferation. For the GO-AgNPs fillers, the results indicate that PLA-1 wt%GO-(1-7) wt% Ag hybrid fibrous mats exhibit excellent antibacterial effect against E. coli, while the PLA-1 wt%GO-Ag mats with higher AgNP loadings show bacterial inhibition toward S. aureus.
PEEK is a high performance thermoplastic having high temperature durability, excellent radiation stability and high mechanical stiffness. The elastic modulus of PEEK can be further enhanced by adding nHA or nHA-MWNT fillers. The mechanical performance and biocompatibility of PEEK-nHA and PEEK/nHA-MWNT nanocomposites have been studied using tensile test, MTT, 2-(4-iodopheny)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-1), alkaline phosphatase and Alizarin red-S measurements. The results show that the elastic modulus of PEEK/15% nHA-1.88%MWNT nanocomposite (7.13 GPa) exceeds the lower limit modulus of human cortical bone (7 GPa). Furthermore, this nanocomposite favors the adhesion, proliferation and differentiation of osteoblasts on its surface.