Critical-sized bone defects remain challenging in the clinical setting. Autologous bone grafting remains preferred by clinicians. However, the use of autologous tissue is associated with donor-site morbidity and limited accessibility to the graft tissue. Advances in the development of synthetic bone substitutes focus on improving their osteoinductive properties. Whereas osteoinductivity has been demonstrated with ceramics, it is still a challenge in case of polymeric composites. One of the approaches to improve the regenerative properties of biomaterials, without changing their synthetic character, is the addition of inorganic ions with known osteogenic and angiogenic properties. We have previously reported that the use of a bioactive composite with high ceramic content composed of poly(ethyleneoxide terephthalate)/poly(butylene terephthalate) (1000PEOT70PBT30, PolyActive, PA) and 50% beta-tricalcium phosphate (β-TCP) with the addition of zinc in a form of a coating of the TCP particles can enhance the osteogenic differentiation of human mesenchymal stromal cells (hMSCs) (3). To further support the regenerative properties of these scaffolds, inorganic ions with known angiogenic properties, copper or cobalt, were added to the coating solution.

β-TCP particles were immersed in a zinc and copper or zinc and cobalt solution with a concentration of 15 or 45 mM. 3D porous scaffolds composed of 1000PEOT70PBT30 and pure or coated β-TCP were additively manufactured by 3D fibre deposition. The osteogenic and angiogenic properties of the fabricated scaffolds were tested in vitro through culture with hMSCs and human umbilical vein endothelial cells, respectively. The materials were further evaluated through ectopic implantation in an in vivo mini-pig model. The early expression of relevant osteogenic gene markers (collagen-1, osteocalcin) of hMSCs was upregulated in the presence of lower concentration of inorganic ions. Further analysis will focus on the evaluation of ectopic bone formation and vascularisation of these scaffolds after implantation in a mini-pig ectopic intramuscular model.

Background

The CoCrMo large bearings had shown a high failure rate, because of metal ion and particle release. Alumina matrix composite (AMC) ball heads have shown to mitigate such phenomena. The aim of this study was to investigate the leaching properties of AMC clinically as well as experimentally.

Background

Increased revision rates and early failure of Metal-on-Metal (MoM) hip replacements are often due to adverse reaction to metal debris (ARMD). ARMD describes numerous symptoms in patients such as pain, osteolysis and soft tissue damage. Cobalt is a major component of MoM joints and can initiate an immune response via activation of the innate immune receptor Toll-like receptor 4 (TLR4). This leads to increased secretion of inflammatory cytokines e.g. interleukin-8 (IL-8). This study investigates whether TLR4-specific antagonists inhibit the inflammatory response to cobalt using IL-8 gene expression and protein secretion as a marker of TLR4 activation.

We have previously observed an increase in total bone mineral density and reduced bone turnover (TRAP5b and osteocalcin) in patients with well-functioning metal-on-metal hip resurfacing (MOMHR). Here, we provide data to support the hypothesis that osteoclast differentiation and function is altered in this patient population, and that this effect is transferrable through their serum.

Patients with well-functioning MOMHR (cases, n=18) at a median follow-up of 8 years were individually matched for gender, age and time-since-surgery to a low-exposure group consisting of patients with THA (controls, n=18). The monocyte fraction of patient peripheral blood was isolated and differentiated into osteoclasts on dentine wafers using RANKL and M-CSF supplemented media (osteoclastogenic media, OM). Cultures were monitored for the onset of resorption, at which point the cells were treated with OM, autologous serum or serum from matched MOMHR/THA donors, all supplemented with RANKL and M-CSF. At the end of the culture, cells were TRAP-stained and quantified using CellD Software Package, Olympus.

When cells were differentiated in standard osteoclastogenic media, the resorbing ability of osteoclasts derived from MOMHR patients was reduced 22%(p<0.0079) compared to THA. The resorbing ability of osteoclasts generated from MOMHR patients and differentiated in autologous serum was reduced 33%(p<0.0001), whilst matched THA serum caused a smaller reduction of 14%(p<0.01). When cells derived from THA patients were differentiated in autologous serum, the resorbing ability of osteoclasts was similarly reduced by 35%(p<0.0001), whilst the matched MOMHR serum also caused a reduction of 21%(p<0.0001).

This data suggests that prior exposure to higher circulating Co and Cr in patients with MOMHR reduces osteoclastogenesis, and that the detrimental effect on the functionality of mature osteoclasts is transferable through the serum. This has implications for systemic bone health of patients with MOMHR or modular taper junctions.

Metal-on-metal (MOM) hip arthroplasty, including resurfacing, has become the subject of recent research and debate. There is the perceived benefit of improved wear rates of bearing surfaces leading to superior durability and performance of these types of implant. An associated feature of MOM bearing surfaces is the generation of metal ions. These can have local and systemic cytotoxic effects. An immunoloigical response has been suggested, however, metal wear debris may cause direct damage to cellular DNA. Studies have shown that release of these ions is related to bearing diameter and component alignment. However, little is known about the relationship between metal ion levels and implant survivorship. The MHRA has published guidelines on the follow-up of patients with MOM implants including measurement of serum ion levels and cross sectional imaging.

Between February 2001 and November 2009, 135 patients (164 hips) had MOM resurfacing arthroplasty at our institution. We report a retrospective analysis of the data generated by review of these patients. Of the 135 patients, 91 were identified for clinical review. Each patient had serum metal ion levels measured, plain AP radiographs of the pelvis examined and, in the presence of raised metal ions, a Metal Artefact Reduction Sequence (MARS) MRI performed. 27 patients (35 hips) had raised metal ion levels (Cobalt and Chromium). Patients with raised metal ion levels had a mean acetabular cup inclination of 52.7 degrees compared with a mean inclination of 48.6 degrees in patients with normal ion levels (p<0.05). MARS MRI in the raised ion group revealed 9 patients with appearances suggestive of ALVAL. A number of these patients had hip revision surgery with the remainder awaiting potential revision.

These findings reflect current evidence suggesting a relationship between sub-optimal component position and raised metal ion levels and an increased rate of ALVAL.