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The Bone & Joint Journal
Vol. 103-B, Issue 7 Supple B | Pages 135 - 144
1 Jul 2021
Kuyl E Shu F Sosa BR Lopez JD Qin D Pannellini T Ivashkiv LB Greenblatt MB Bostrom MPG Yang X

Aims. Aseptic loosening is a leading cause of uncemented arthroplasty failure, often accompanied by fibrotic tissue at the bone-implant interface. A biological target, neutrophil extracellular traps (NETs), was investigated as a crucial connection between the innate immune system’s response to injury, fibrotic tissue development, and proper bone healing. Prevalence of NETs in peri-implant fibrotic tissue from aseptic loosening patients was assessed. A murine model of osseointegration failure was used to test the hypothesis that inhibition (through Pad4-/- mice that display defects in peptidyl arginine deiminase 4 (PAD4), an essential protein required for NETs) or resolution (via DNase 1 treatment, an enzyme that degrades the cytotoxic DNA matrix) of NETs can prevent osseointegration failure and formation of peri-implant fibrotic tissue. Methods. Patient peri-implant fibrotic tissue was analyzed for NETs biomarkers. To enhance osseointegration in loose implant conditions, an innate immune system pathway (NETs) was either inhibited (Pad4-/- mice) or resolved with a pharmacological agent (DNase 1) in a murine model of osseointegration failure. Results. NETs biomarkers were identified in peri-implant fibrotic tissue collected from aseptic loosening patients and at the bone-implant interface in a murine model of osseointegration failure. Inhibition (Pad4-/-) or resolution (DNase 1) of NETs improved osseointegration and reduced fibrotic tissue despite loose implant conditions in mice. Conclusion. This study identifies a biological target (NETs) for potential noninvasive treatments of aseptic loosening by discovering a novel connection between the innate immune system and post-injury bone remodelling caused by implant loosening. By inhibiting or resolving NETs in an osseointegration failure murine model, fibrotic tissue encapsulation around an implant is reduced and osseointegration is enhanced, despite loose implant conditions. Cite this article: Bone Joint J 2021;103-B(7 Supple B):135–144


The Bone & Joint Journal
Vol. 100-B, Issue 7 | Pages 882 - 890
1 Jul 2018
Bertrand J Delfosse D Mai V Awiszus F Harnisch K Lohmann CH

Aims. Early evidence has emerged suggesting that ceramic-on-ceramic articulations induce a different tissue reaction to ceramic-on-polyethylene and metal-on-metal bearings. Therefore, the aim of this study was to investigate the tissue reaction and cellular response to ceramic total hip arthroplasty (THA) materials in vitro, as well as the tissue reaction in capsular tissue after revision surgery of ceramic-on-ceramic THAs. Patients and Methods. We investigated tissue collected at revision surgery from nine ceramic-on-ceramic articulations. we compared our findings with tissue obtained from five metal-on-metal THA revisions, four ceramic-on-polyethylene THAs, and four primary osteoarthritis synovial membranes. The latter were analyzed to assess the amount of tissue fibrosis that might have been present at the time of implantation to enable evaluation, in relation to implantation time, of any subsequent response in the tissues. Results. There was a significant increase in tissue fibrosis with implantation time for all implant types tested. Interestingly, the tissue fibrosis in ceramic-on-ceramic THAs was significantly increased compared with metal-on-metal and ceramic-on-polyethylene. Additionally, we found ceramic wear particles in the periprosthetic tissue of ceramic implants. Fibroblasts responded with expression of cytokines when cultured on alumina-toughened zirconia (ATZ) and zirconia-toughened alumina (ZTA) ceramic surfaces. This response was more pronounced on ATZ ceramics compared with ZTA ceramics. The same inflammatory response was observed with peripheral blood mononuclear cells (PBMCs) cultured on ZTA and ATZ. Conclusion. Our findings therefore, corroborate the previous findings that ceramic-on-ceramic periprosthetic revision tissue is fibrous and offer an explanation for this observation. We detected a long-term inflammatory response of PBMCs and an inflammatory response of fibroblasts to ATZ and ZTA ceramic. These findings partially explain the fibrotic tissue change in periprosthetic tissue of ceramic-on-ceramic bearings. Cite this article: Bone Joint J 2018;100-B:882–90


The Bone & Joint Journal
Vol. 102-B, Issue 7 Supple B | Pages 3 - 10
1 Jul 2020
Sosa BR Niu Y Turajane K Staats K Suhardi V Carli A Fischetti V Bostrom M Yang X

Aims

Current treatments of prosthetic joint infection (PJI) are minimally effective against Staphylococcus aureus biofilm. A murine PJI model of debridement, antibiotics, and implant retention (DAIR) was used to test the hypothesis that PlySs2, a bacteriophage-derived lysin, can target S. aureus biofilm and address the unique challenges presented in this periprosthetic environment.

Methods

The ability of PlySs2 and vancomycin to kill biofilm and colony-forming units (CFUs) on orthopaedic implants were compared using in vitro models. An in vivo murine PJI model of DAIR was used to assess the efficacy of a combination of PlySs2 and vancomycin on periprosthetic bacterial load.


The Bone & Joint Journal
Vol. 102-B, Issue 7 Supple B | Pages 116 - 121
1 Jul 2020
Heise G Black CM Smith R Morrow BR Mihalko WM

Aims

This study aimed to determine if macrophages can attach and directly affect the oxide layers of 316L stainless steel, titanium alloy (Ti6Al4V), and cobalt-chromium-molybdenum alloy (CoCrMo) by releasing components of these alloys.

Methods

Murine peritoneal macrophages were cultured and placed on stainless steel, CoCrMo, and Ti6Al4V discs into a 96-well plate. Cells were activated with interferon gamma and lipopolysaccharide. Macrophages on stainless steel discs produced significantly more nitric oxide (NO) compared to their control counterparts after eight to ten days and remained elevated for the duration of the experiment.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 8 | Pages 1011 - 1016
1 Aug 2011
Langton DJ Jameson SS Joyce TJ Gandhi JN Sidaginamale R Mereddy P Lord J Nargol AVF

There is widespread concern regarding the incidence of adverse soft-tissue reactions after metal-on-metal (MoM) hip replacement. Recent National Joint Registry data have shown clear differences in the rates of failure of different designs of hip resurfacing. Our aim was to update the failure rates related to metal debris for the Articular Surface Replacement (ASR). A total of 505 of these were implanted. Kaplan-Meier analysis showed a failure rate of 25% at six years for the ASR resurfacing and of 48.8% for the ASR total hip replacement (THR). Of 257 patients with a minimum follow-up of two years, 67 (26.1%) had a serum cobalt concentration which was greater than 7 μg/l. Co-ordinate measuring machine analysis of revised components showed that all patients suffering adverse tissue reactions in the resurfacing group had abnormal wear of the bearing surfaces. Six THR patients had relatively low rates of articular wear, but were found to have considerable damage at the trunion-taper interface. Our results suggest that wear at the modular junction is an important factor in the development of adverse tissue reactions after implantation of a large-diameter MoM THR


The Bone & Joint Journal
Vol. 98-B, Issue 2 | Pages 179 - 186
1 Feb 2016
Berber R Skinner J Board T Kendoff D Eskelinen A Kwon Y Padgett DE Hart A

Aims

There are many guidelines that help direct the management of patients with metal-on-metal (MOM) hip arthroplasties. We have undertaken a study to compare the management of patients with MOM hip arthroplasties in different countries.

Methods

Six international tertiary referral orthopaedic centres were invited to participate by organising a multi-disciplinary team (MDT) meeting, consisting of two or more revision hip arthroplasty surgeons and a musculoskeletal radiologist. A full clinical dataset including history, blood tests and imaging for ten patients was sent to each unit, for discussion and treatment planning. Differences in the interpretation of findings, management decisions and rationale for decisions were compared using quantitative and qualitative methods.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 7 | Pages 886 - 889
1 Jul 2011
Bremer AK Kalberer F Pfirrmann CWA Dora C

The direct anterior approach in total hip replacement anatomically offers the chance to minimise soft-tissue trauma because an intermuscular and internervous plane is explored. This motivated us to abandon our previously used transgluteal approach and to adopt the direct anterior approach for total hip replacement. Using MRI, we performed a retrospective comparative study of the direct anterior approach with the transgluteal approach. There were 25 patients in each group. At one year post-operatively all the patients underwent MRI of their replaced hips. A radiologist graded the changes in the soft-tissue signals in the abductor muscles. The groups were similar in terms of age, gender, body mass index, complexity of the reconstruction and absence of symptoms.

Detachment of the abductor insertion, partial tears and tendonitis of gluteus medius and minimus, the presence of peri-trochanteric bursal fluid and fatty atrophy of gluteus medius and minimus were significantly less pronounced and less frequent when the direct anterior approach was used. There was no significant difference in the findings regarding tensor fascia lata between the two approaches.

We conclude that use of the direct anterior approach results in a better soft-tissue response as assessed by MRI after total hip replacement. However, the impact on outcome needs to be evaluated further.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 11 | Pages 1515 - 1521
1 Nov 2010
Clauss M Ilchmann T Zimmermann P Ochsner PE

The aim of this study was to obtain detailed long-term data on the cement-bone interface in patients with cemented stems, implanted using the constrained fixation technique. A total of eight stems were removed together with adjacent bone during post-mortem examinations of patients with well-functioning prostheses. Specimens were cut at four defined levels, contact radiographs were obtained for each level, and slices were prepared for histological analysis. Clinical data, clinical radiographs, contact radiographs and histological samples were examined for signs of loosening and remodelling. The mean radiological follow-up was 9.6 years and all stems were well-fixed, based on clinical and radiological criteria. Contact radiographs revealed an incomplete cement mantle but a complete filling of the medullary canal for all implants. Various amounts of polyethylene particles were evident at the cement-bone interface of seven stems, with no accompanying inflammatory reaction. Cortical atrophy and the formation of an ‘inner cortex’ were confirmed in six of eight stems by contact radiographs and histology, but were only visible on two clinical radiographs.

Our results confirm that a complete cement mantle is not essential for the survival of Müller straight stems into the mid term, and support our hypothesis that no benefit to long-term survival can be expected from modern cementing techniques.