Bone and metal - an orthopaedic perspective on osseointegration of metals

The area of implant osseointegration is of major importance, given the predicted significant rise in the number of orthopaedic procedures and an increasingly ageing population. Osseointegration is a complex process involving a number of distinct mechanisms affected by the implant bulk properties and surface characteristics. Our understanding and ability to modify these mechanisms through alterations in implant design is continuously expanding. The following review considers the main aspects of material and surface alterations in metal implants, and the extent of their subsequent influence on osseointegration. Clinically, osseointegration results in asymptomatic stable durable fixation of orthopaedic implants. The complexity of achieving this outcome through incorporation and balance of contributory factors is highlighted through a clinical case report

The Biologic Response to Polyetheretherketone (PEEK) Wear Particles in Total Joint Replacement: A Systematic Review

Background: Polyetheretherketone (PEEK) and its composites are polymers resistant to fatigue strain, radiologically transparent, and have mechanical properties suitable for a range of orthopaedic applications. In bulk form, PEEK composites are generally accepted as biocompatible. In particulate form, however, the biologic response relevant to joint replacement devices remains unclear. The biologic response to wear particles affects the longevity of total joint arthroplasties. Particles in the phagocytozable size range of 0.1 µm to 10 µm are considered the most biologically reactive, particularly particles with a mean size of < 1 µm. This systematic review aimed to identify the current evidence for the biological response to PEEK-based wear debris from total joint arthroplasties. Questions/purposes: (1) What are the quantitative characteristics of PEEK-based wear particles produced by total joint arthroplasties? (2) Do PEEK wear particles cause an adverse biologic response when compared with UHMWPE or a similar negative control biomaterial? (3) Is the biologic response affected by particle characteristics? Methods: Embase and Ovid Medline databases were searched for studies that quantified PEEK-based particle characteristics and/or investigated the biologic response to PEEK-based particles relevant to total joint arthroplasties. The keyword search included brands of PEEK (eg, MITCH, MOTIS) or variations of PEEK types and nomenclature (eg, PAEK, CFR-PEEK) in combination with types of joint (eg, hip, knee) and synonyms for wear debris or immunologic response (eg, particles, cytotoxicity). Peer-reviewed studies, published in English, investigating total joint arthroplasty devices and cytotoxic effects of PEEK particulates were included. Studies investigating devices without articulating bearings (eg, spinal instrumentation devices) and bulk material or contact cytotoxicity were excluded. Of 129 studies, 15 were selected for analysis and interpretation. No studies were found that isolated and characterized PEEK wear particles from retrieved periprosthetic human tissue samples. Results: In the four studies that quantified PEEK-based particles produced using hip, knee, and spinal joint replacement simulators, the mean particle size was 0.23 µm to 2.0 µm. The absolute range reported was approximately 0.01 µm to 50 µm. Rod-like carbon particulates and granular-shaped PEEK particles were identified in human tissue by histologic analysis. Ten studies, including six animal models (rat, mouse, and rabbit), three cell line experiments, and two human tissue retreival studies, investigated the biologic response to PEEK-based particles. Qualitative histologic assessments showed immunologic cell infiltration to be similar for PEEK particles when compared with UHMWPE particles in all six of the animal studies identified. However, increased inflammatory cytokine release (such as tumor necrosis factor-α) was identified in only one in vitro study, but without substantial suppression in macrophage viability. Only one study tested the effects of particle size on cytotoxicity and found the largest unfilled PEEK particles (approximately 13 µm) to have a toxic effect; UHMWPE particles in the same size range showed a similar cytotoxic effect. Conclusions: Wear particles produced by PEEK-based bearings were, in almost all cases, in the phagocytozable size range (0.1-10 µm). The studies that evaluated the biologic response to PEEK-based particles generally found cytotoxicity to be within acceptable limits relative to the UHMWPE control, but inconsistent when inflammatory cytokine release was considered. Clinical Relevance: To translate new and advanced materials into clinical use more quickly, the clinical relevance and validity of preclinical tests need to be improved. To achieve this for PEEK-based devices, human tissue retrieval studies including subsequent particle isolation and characterization analyses are required. In vitro cell studies using isolated wear particles from tissue or validated joint replacement simulators, instead of manufactured particles, are also required

Bioactive ceramic-reinforced composites for bone augmentation

Biomaterials have been used to repair the human body for millennia, but it is only since the 1970s that man-made composites have been used. Hydroxyapatite (HA)-reinforced polyethylene (PE) is the first of the ‘second-generation’ biomaterials that have been developed to be bioactive rather than bioinert. The mechanical properties have been characterized using quasi-static, fatigue, creep and fracture toughness testing, and these studies have allowed optimization of the production method. The in vitro and in vivo biological properties have been investigated with a range of filler content and have shown that the presence of sufficient bioactive filler leads to a bioactive composite. Finally, the material has been applied clinically, initially in the orbital floor and later in the middle ear. From this initial combination of HA in PE other bioactive ceramic polymer composites have been developed

In vitro analyses of the toxicity, immunological, and gene expression effects of cobalt-chromium alloy wear debris and Co ions derived from metal-on-metal hip implants

Joint replacement has proven to be an extremely successful and cost-effective means of relieving arthritic pain and improving quality of life for recipients. Wear debris-induced osteolysis is, however, a major limitation and causes orthopaedic implant aseptic loosening, and various cell types including macrophages, monocytes, osteoblasts, and osteoclasts, are involved. During the last few years, there has been increasing concern about metal-on-metal (MoM) hip replacements regarding adverse reactions to metal debris associated with the MoM articulation. Even though MoM-bearing technology was initially aimed to extend the durability of hip replacements and to reduce the requirement for revision, they have been reported to release at least three times more cobalt and chromium ions than metal-on-polyethylene (MoP) hip replacements. As a result, the toxicity of metal particles and ions produced by bearing surfaces, both locally in the periprosthetic space and systemically, became a concern. Several investigations have been carried out to understand the mechanisms responsible for the adverse response to metal wear debris. This review aims at summarising in vitro analyses of the toxicity, immunological, and gene expression effects of cobalt ions and wear debris derived from MoM hip implants

Biological response to prosthetic debris.

Joint arthroplasty had revolutionized the outcome of orthopaedic surgery. Extensive and collaborative work of many innovator surgeons had led to the development of durable bearing surfaces, yet no single material is considered absolutely perfect. Generation of wear debris from any part of the prosthesis is unavoidable. Implant loosening secondary to osteolysis is the most common mode of failure of arthroplasty. Osteolysis is the resultant of complex contribution of the generated wear debris and the mechanical instability of the prosthetic components. Roughly speaking, all orthopedic biomaterials may induce a universal biologic host response to generated wear débris with little specific characteristics for each material; but some debris has been shown to be more cytotoxic than others. Prosthetic wear debris induces an extensive biological cascade of adverse cellular responses, where macrophages are the main cellular type involved in this hostile inflammatory process. Macrophages cause osteolysis indirectly by releasing numerous chemotactic inflammatory mediators, and directly by resorbing bone with their membrane microstructures. The bio-reactivity of wear particles depends on two major elements: particle characteristics (size, concentration and composition) and host characteristics. While any particle type may enhance hostile cellular reaction, cytological examination demonstrated that more than 70% of the debris burden is constituted of polyethylene particles. Comprehensive understanding of the intricate process of osteolysis is of utmost importance for future development of therapeutic modalities that may delay or prevent the disease progression

Clinical relevance of corrosion patterns attributed to inflammatory cell-induced corrosion: A retrieval study

In vitro studies have shown that human osteoclasts can corrode stainless steel and titanium leading to the production of metal ions responsible for inflammatory reactions. Moreover, traces of cellular activities on metal orthopaedic explants have recently been reported as inflammatory cell-induced (ICI) corrosion being the result of the cells sealing on the metal surfaces and releasing reactive oxygen species (ROS) through Fenton-like reactions. The extent and clinical relevance of this phenomenon has yet to be understood. We analysed a cohort of 100 CoCr alloy hips collected at our retrieval centre; we performed macroscopic and microscopic screening and used statistical analysis to correlate our findings with implant and clinical variables. We found that 59% of our implants had evidence of surface damage consistent with what has previously been described as cell-induced corrosion. There was a significant association between the patterns and aseptic loosening for the ASR modular (r = -0.488, p = 0.016) and the Durom modular (r = 0.454, p = 0.026). This is the largest implant retrieval study to examine the phenomena of so-called ICI corrosion and is the first to investigate its clinical relevance. We recommend further work to determine the role of cells in the damage patterns observed. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2015

Inflammatory cell-induced corrosion in total knee arthroplasty: a retrieval study

Metal release in patients with joint replacements is associated with local tissue reactions, pain, and ultimately revision of implants. One of the causes of this metal loss is speculated to be due to a mechanism of inflammatory cell-induced corrosion (ICIC). In this knee retrieval study, we aimed to: (1) identify the extent and location of ICI corrosion patterns on our femoral and tibial components and (2) correlate our findings with implant and clinical information. We investigated 28 femoral and 9 tibial components made of polished CoCr for presence of ICIC, using macroscopic and microscopic screening and statistical analyses to identify any significant correlations between our results and clinical information. We found that 71% of femoral and 100% of tibial components showed evidence of ICIC and significantly more was present on non-contacting regions (p < 0.0001). We found a significant correlation between the presence of ICIC and instability (p = 0.0113) and a significant difference between poster stabilized and cruciate retaining designs in the amount of ICIC on internal edges (p = 0.0375). This corrosion pattern was prevalent in our series of knee retrievals and may help explain some of the mechanisms of material loss that may occur in vivo