H. Leenders

Application of porous PEO/PBT copolymers for bone replacement

A range of polyethylene oxide/polybutylene terephthalate (PEO/PBT) copolymers (70-30% PEO) was investigated for nonloadbearing bone replacement application. Porous PEO/PBT cylinders (d = 5 mm, h = 7 mm) were implanted transcortically in the diaphyseal femur of 10 goats, and the animals were sacrificed at 3, 6, 9, 12, and 26 weeks. Qualitative evaluation was performed using light and fluorescence microscopy, scanning electron microscopy, and back-scatter electron imaging with an attached X-ray microanalysis system. The percentage of bone ingrowth and the percentage of bone contact in the pore region were quantitatively assessed using undecalcified histological sections. The hydrogel properties of the PEO/PBT copolymers provided a rapid closure of the defect upon press-fit implantation, due to postoperative water uptake and subsequent swelling behavior of the materials. Bridging of the defect by bone and the occurrence of bone bonding were observed 6 weeks postoperatively for the material with the highest PEO content (70/30). For the 60/40 and 55/45 PEO/PBT proportions, union of the defect and bone bonding were observed at 9 and 12 weeks, respectively. The stiffer 40/60 and 30/70 PEO/PBT implants showed bridging of the 5-mm gap after 12 weeks, but did not reveal bone bonding up to 26 weeks. Peripheral fragmentation, mainly in the marrow cavity, was found for the 70/30 material at 12 weeks and had increased at 26 weeks. Degradation was not seen for the other materials. The histomorphometrical data confirmed the microscopical observations and demonstrated a direct relation between PEO content in the PEO/PBT co-polymers, the rate of bone ingrowth, and the amount of bone contact. Porous PEO/PBT copolymers are degradable, bone-bonding elastomeric substrates with favorable handling properties and a high percentage of bone ingrowth (69-78 at 26 weeks). It was therefore concluded that PEO/ PBT copolymers are highly promising materials for bone-replacement surgery.

Bone-bonding behaviour of poly(ethylene oxide)-polybutylene terephthalate copolymer coatings and bulk implants: a comparative study

A range of poly(ethylene oxide)-polybutylene terephthalate (PEO-PBT) copolymers (70-30% PEO), both as coating on titanium alloy as well as bulk cylinders, was press-fit implanted in the diaphyseal femur of 16 goats. At early survival times (4 wk), a high degree of cortical bone contact was observed for bulk implants using light microscopy and this was confirmed by backscatter electron microscopy. This was attributed to the swelling behaviour of PEO-PBT copolymers. At this stage, bone contact was also revealed for coated implants, but to a lesser extent. At a later stage (12 wk), bone bonding was demonstrated both morphologically and by X-ray microanalysis, at the interface of 70:30 PEO-PBT bulk as well as 70:30 PEO-PBT-coated implants. Bone bonding increased with time (26 and 52 wk) for this PEO-PBT proportion and was also observed for 60:40 and 55:45 implants, although less frequently. For 40:60 and 30:70 PEO-PBT proportions, bone bonding was not shown. Based on these qualitative data, it was not possible to differentiate between coated and bulk implants with respect to bone bonding. This study demonstrated that the application of PEO-PBT elastomers as coatings does not alter the bone-bonding properties. It was therefore concluded that PEO-PBT coatings are beneficial over the bone-bonding but brittle ceramic coatings, due to their flexibility. In addition, the bone-bonding capacities of these PEO-PBT coatings surpass the non-bonding behaviour of currently available flexible coatings.

Comparison of the cytotoxicity of molybdenum as powder and as alloying element in a niobium–molybdenum alloy

Commercially pure metal niobium (c.p. Nb) as well as niobium–molybdenum (Nb–Mo) alloys were produced following several powder metallurgical routes. In brief, niobium and molybdenum powders were blended and milled in order to form Nb–Mo alloys. The alloy powders and the c.p. Nb were then either pressed and sintered, or cold isostatically pressed followed by hot isostatically pressing. In order to assess the cytotoxicity of the c.p. Nb and c.p. Mo powders, a 72 h minimal essential medium-extraction test was performed according to ISO/EN 10993–5. The cytotoxicity of the c.p. Nb metal and the Nb–Mo alloys was tested in a 72 h direct contact test. Compared to a negative control (UHMWPE), c.p. Nb was non-toxic, but c.p. Mo was moderately toxic. None of the powder metallurgically produced materials were toxic. Neither differences in molybdenum concentration, nor in porosity of the samples, due to different production routes, had any influence on the toxicity of the materials. Rat bone marrow cultures showed that only on c.p. Nb was a mineralized extracellular matrix formed, while on the more porous Nb–Mo alloys, cell growth was observed, but no mineralization. In conclusion, c.p. Mo powder is moderately toxic, however, as an alloying element it is non-toxic. Material porosity seems to influence differentiation of bone tissue in vitro.

Gene expression and protein activity in bone-bonding and non-bonding PEO/PBT copolymers

The formation of a reactive carbonate-apatite surface is generally considered a critical step for bone-bonding. However, the contribution of proteins in the establishment of bone-bonding is debatable. In the current study, osteocalcin, osteopontin and β-actin mRNA expression and alkaline phosphatase activity were therefore determined in different porous substrates loaded with marrow after subcutaneous implantation for 2 weeks. Two polyethylene oxide (PEO)/polybutylene terephthalate (PBT) copolymers were used for this purpose. First, an 80/20 PEO/PBT which generates a carbonate-apatite surface and bonds to bone rapidly. Second, a 30/70 PEO/PBT which previously did not show bone-bonding up to 1 year postoperative. Bone had formed within the pores and occasionally at the calcified surface of the 80/20 materials. In contrast, 30/70 materials did not calcify and bone was not found in the pores. Despite these morphological differences, gene expression and protein activity was similar in 80/20 and 30/70 PEO/PBT materials. These results suggested that bone-bonding of PEO/PBT copolymers is more likely to depend on the formation of a carbonate-apatite surface than on a specific influence of a bioactive material on osteogenic cells.