Implant failure resulting from corrosion processes within modular junctions is a major concern in THA. Our results suggest that implant alloy microstructure is not sufficiently standardized and may also dictate specific corrosion modes and subsequent metal ion release.

Material degradation within taper junctions of modular total hip replacements remains of great concern. Imprinting and column damage are two damage modes that frequently occur on head taper surfaces. Both can cover large areas and therefore can be associated with significant material loss. It was the purpose of this study to determine the prevalence of imprinting and column damage on a group of retrievals collected at our medical center and to identify damage pathways on selected cases. We asked two research questions: (1) How do CoCrMo stems imprint into CoCrMo heads? (2) Does alloy microstructure influence the column damage pattern in CoCrMo heads? In order to answer these questions, we conducted a retrieval study on moderately to severely worn femoral head taper surfaces that were paired with stems of different materials. All components were viewed under a stereo-light microscope to determine the presence of imprinting and column damage. Selected cases were further studied by means of scanning electron microscope, interferometry, and metallography to determine damage mode and the potential role of alloy microstructure. Our results demonstrated that imprinting is independent of the stem material but highly dependent on its topography. The imprinting process is at least initially driven by fretting and the generation of oxide particles. Column damage on the other hand is highly dependent on the microstructure of wrought CoCrMo alloys, which can exhibit banding resulting from slight alloy segregations that were characterized by molybdenum depletion. Therefore, column damage may be prevented by avoiding banding of the alloy during the thermomechanical processing. This study demonstrates that it is important to consider differences among the occurring degradation mechanisms and to understand how they relate to material and design factors.

Mitochondrial dysfunction has been implicated in the pathophysiology of neurodegenerative disorders, including multiple sclerosis (MS). To date, the investigation of mitochondrial dysfunction in MS has focused exclusively on neurons, with no studies exploring whether dysregulation of mitochondrial bioenergetics and/or genetics in oligodendrocytes might be associated with the etiopathogenesis of MS and other demyelinating syndromes. To address this question, we established a mouse model where mitochondrial DNA (mtDNA) double-strand breaks (DSBs) were specifically induced in myelinating oligodendrocytes (PLP:mtPstI mice) by expressing a mitochondrial-targeted endonuclease, mtPstI, starting at 3 weeks of age. In both female and male mice, DSBs of oligodendroglial mtDNA caused impairment of locomotor function, chronic demyelination, glial activation, and axonal degeneration, which became more severe with time of induction. In addition, after short transient induction of mtDNA DSBs, PLP:mtPstI mice showed an exacerbated response to experimental autoimmune encephalomyelitis. Together, our data demonstrate that mtDNA damage can cause primary oligodendropathy, which in turn triggers demyelination, proving PLP:mtPstI mice to be a useful tool to study the pathological consequences of mitochondrial dysfunction in oligodendrocytes. In addition, the demyelination and axonal loss displayed by PLP:mtPstI mice recapitulate some of the key features of chronic demyelinating syndromes, including progressive MS forms, which are not accurately reproduced in the models currently available. For this reason, the PLP:mtPstI mouse represents a unique and much needed platform for testing remyelinating therapies. In this study, we show that oligodendrocyte-specific mitochondrial DNA double-strand breaks in PLP:mtPstI mice cause oligodendrocyte death and demyelination associated with axonal damage and glial activation. Hence, PLP:mtPstI mice represent a unique tool to study the pathological consequences of mitochondrial dysfunction in oligodendrocytes, as well as an ideal platform to test remyelinating and neuroprotective agents.

Background Fretting and corrosion in metal-on-polyethylene total hip arthoplasty (THA) modular junctions can cause adverse tissue reactions that are responsible for 2% to 5% of revision surgeries. Damage within cobalt-chromium-molybdenum (CoCrMo) alloy femoral heads can progress chemically and mechanically, leading to damage modes such as column damage, imprinting, and uniform fretting damage. At present, it is unclear which of these damage modes are most detrimental and how they may be linked to implant alloy metallurgy. The alloy microstructure exhibits microstructural features such as grain boundaries, hard phases, and segregation bands, which may enable different damage modes, higher material loss, and the potential risk of adverse local tissue reactions. Questions/purposes In this study, we asked: (1) How prevalent is chemically dominated column damage compared with mechanically dominated damage modes in severely damaged metal-on-polyethylene THA femoral heads made from wrought CoCrMo alloy? (2) Is material loss greater in femoral heads that underwent column damage? (3) Do material loss and the presence of column damage depend on alloy microstructure as characterized by grain size, hard phase content, and/or banding? Methods Surgically retrieved wrought CoCrMo modular femoral heads removed between June 2004 and June 2019 were scored using a modified version of the Goldberg visually based scoring system. Of the total 1002 heads retrieved over this period, 19% (190 of 1002) were identified as severely damaged, exhibiting large areas of fretting scars, black debris, pits, and/or etch marks. Of these, 43% (81 of 190) were excluded for metal-on-metal articulations, alternate designs (such as bipolar, dual-mobility, hemiarthroplasty, metal adaptor sleeves), or previous sectioning of the implant for past studies. One sample was excluded retroactively as metallurgical analysis revealed that it was made of cast alloy, yielding a total of 108 for further analysis. Information on patient age (57 ± 11 years) and sex (56% [61 of 108] were males), reason for removal, implant time in situ (99 ± 78 months), implant manufacturer, head size, and the CoCrMo or titanium-based stem alloy pairing were collected. Damage modes and volumetric material loss within the head tapers were identified using an optical coordinate measuring machine. Samples were categorized by damage mode groups by column damage, imprinting, a combination of column damage and imprinting, or uniform fretting. Metallurgical samples were processed to identify microstructural characteristics of grain size, hard phase content, and banding. Nonparametric Mann-Whitney U and Kruskal-Wallis statistical tests were used to examine volumetric material loss compared with damage mode and microstructural features, and linear regression was performed to correlate patient- and manufacturer-specific factors with volumetric material loss. Results Chemically driven column damage was seen in 48% (52 of 108) of femoral heads, with 34% (37 of 108) exhibiting a combination of column damage and imprinting, 12% (13 of 108) of heads displaying column damage and uniform fretting, and 2% (2 of 108) exhibiting such widespread column damage that potentially underlying mechanical damage modes could not be verified. Implants with column damage showed greater material loss than those with mechanically driven damage alone, with median (range) values of 1.2 mm3 (0.2 to 11.7) versus 0.6 mm3 (0 to 20.7; p = 0.03). Median (range) volume loss across all femoral heads was 0.9 mm3 (0 to 20.7). Time in situ, contact area, patient age, sex, head size, manufacturer, and stem alloy type were not associated with volumetric material loss. Banding of the alloy microstructure, with a median (range) material loss of 1.1 mm3 (0 to 20.7), was associated with five times higher material loss compared with those with a homogeneous microstructure, which had a volume loss of 0.2 mm3 (0 to 4.1; p = 0.02). Hard phase content and grain size showed no correlation with material loss. Conclusion Chemically dominated column damage was a clear indicator of greater volume loss in this study sample of 108 severely damaged heads. Volumetric material loss strongly depended on banding (microstructural segregations) within the alloy. Banding of the wrought CoCrMo microstructure should be avoided during the manufacturing process to reduce volumetric material loss and the release of corrosion products to the periprosthetic tissue. Clinical Relevance Approximately 30% of THAs rely on wrought CoCrMo femoral heads. Most femoral heads in this study exhibited a banded microstructure that was associated with larger material loss and the occurrence of chemically dominated column damage. This study suggests that elimination of banding from the alloy could substantially reduce the release of implant debris in vivo, which could potentially also reduce the risk of adverse local tissue reactions to implant debris.

Implant debris generated by wear and corrosion is a prominent cause of joint replacement failure. This study utilized Fourier Transform InfraRed spectroscopic Imaging (FTIR-I) to gain a better understanding of the chemical structure of implant debris and its impact on the surrounding biological environment. Therefore, retrieved joint capsule tissue from five total hip replacement patients was analyzed. All five cases presented different implant designs and histopathological patterns. All tissue samples were formalin-fixed and paraffin-embedded. Unstained, 5μm thick sections were prepared. The unstained sections were placed on BaF 2 windows and deparaffinized with xylene prior to analysis. FTIR-I data were collected at a spectral resolution of 4 cm −1 using an Agilent Cary 670 spectrometer coupled with Cary 620 FTIR microscope. The results of study demonstrated that FTIR-I is a powerful tool that can be used complimentary to the existing histopathological evaluation of tissue. FTIR-I was able to distinguish areas with different cell types (macrophages, lymphocytes). Small, but distinct differences could be detected depending on the state of cells (viable, necrotic) and depending on what type of debris was present (polyethylene (PE), suture material and metal oxides). Although, metal oxides were mainly below the measurable range of FTIR-I, the infrared spectra of tissues exhibited noticeable difference in their presence. Tens of micrometer sized polyethylene particles could be easily imaged, but also accumulations of submicron particles could be detected within macrophages. FTIR-I was also able to distinguish between PE debris, and other birefringent materials such as suture. Chromiumphosphate particles originating from corrosion processes within modular taper junctions of hip implants could be identified and easily distinguished from other phosphorous materials such as bone. In conclusion, this study successfully demonstrated that FTIR-I is a useful tool that can image and determine the biochemical information of retrieved tissue samples over tens of square millimeters in a completely label free, non-destructive, and objective manner. The resulting chemical images provide a deeper understanding of the chemical nature of implant debris and their impact on chemical changes of the tissue within which they are embedded.