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The Journal of Bone & Joint Surgery British Volume
Vol. 73-B, Issue 4 | Pages 559 - 563
1 Jul 1991
Witt J Swann M

Thirteen total hip replacements with titanium alloy femoral components required revision for loosening at an average of two years after implantation. At revision the soft tissues around the implant were darkly stained and a proliferative membrane had invaded the cement-bone interface. The femoral components showed polishing of parts of their shot-blasted surfaces. Histology showed a fibroblastic reaction with abundant titanium lying free and within histiocytes, and a scanty foreign-body giant-cell reaction. Surface analysis of the removed femoral components and chemical analysis of the excised tissues is described. Tissue reaction in response to the metal-wear debris may have contributed to the early failure of these implants.


The Bone & Joint Journal
Vol. 98-B, Issue 8 | Pages 1062 - 1068
1 Aug 2016
Singh G Deutloff N Maertens N Meyer H Awiszus F Feuerstein B Roessner A Lohmann CH

Aims. Tissue responses to debris formed by abrasion of polymethylmethacrylate (PMMA) spacers at two-stage revision arthroplasty for prosthetic joint infection are not well described. We hypothesised that PMMA debris induces immunomodulation in periprosthetic tissues. Patients and Methods. Samples of tissue were taken during 35 two-stage revision arthroplasties (nine total hip and 26 total knee arthroplasties) in patients whose mean age was 67 years (44 to 85). Fourier transform infrared microscopy was used to confirm the presence of PMMA particles. Histomorphometry was performed using Sudan Red and Haematoxylin-Eosin staining. CD-68, CD-20, CD-11(c), CD-3 and IL-17 antibodies were used to immunophenotype the inflammatory cells. All slides were scored semi-quantitatively using the modified Willert scoring system. Results. The mean CD-68 scores did not show any significant change during the six weeks between the stages. Perivascular and diffuse scores showed significant difference in CD-3, CD-20, CD-11(c) and IL-17. At the time of re-implantation, a shift in the pattern of the expression of dendritic cells towards a perivascular arrangement and towards the periphery of PMMA particles was observed. Positive microbiological cultures were found at the time of re-implantation in three patients. Five further revisions were required for other reasons. Conclusion. Our results represent a biological reaction of the synovial tissues to spacers with a less diffuse expression of dendritic cells and an increased expression of perivascular lymphocytes. The use of spacers in two-stage revision for infection probably induces an immunomodulation of synovial tissues. Cite this article: Bone Joint J 2016;98-B:1062–8


The Bone & Joint Journal
Vol. 97-B, Issue 7 | Pages 917 - 923
1 Jul 2015
Singh G Nuechtern JV Meyer H Fiedler GM Awiszus F Junk-Jantsch S Bruegel M Pflueger G Lohmann CH

The peri-prosthetic tissue response to wear debris is complex and influenced by various factors including the size, area and number of particles. We hypothesised that the ‘biologically active area’ of all metal wear particles may predict the type of peri-prosthetic tissue response. . Peri-prosthetic tissue was sampled from 21 patients undergoing revision of a small diameter metal-on-metal (MoM) total hip arthroplasty (THA) for aseptic loosening. An enzymatic protocol was used for tissue digestion and scanning electron microscope was used to characterise particles. Equivalent circle diameters and particle areas were calculated. Histomorphometric analyses were performed on all tissue specimens. Aspirates of synovial fluid were collected for analysis of the cytokine profile analysis, and compared with a control group of patients undergoing primary THA (n = 11) and revision of a failed ceramic-on-polyethylene arthroplasty (n = 6). . The overall distribution of the size and area of the particles in both lymphocyte and non-lymphocyte-dominated responses were similar; however, the subgroup with lymphocyte-dominated peri-prosthetic tissue responses had a significantly larger total number of particles. . 14 cytokines (interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, interferon (IFN)-γ, and IFN-gamma-inducible protein 10), chemokines (macrophage inflammatory protein (MIP)-1α and MIP-1ß), and growth factors (granulocyte macrophage colony stimulating factor (GM-CSF) and platelet derived growth factor) were detected at significantly higher levels in patients with metal wear debris compared with the control group. . Significantly higher levels for IL-1ß, IL-5, IL-10 and GM-CSF were found in the subgroup of tissues from failed MoM THAs with a lymphocyte-dominated peri-prosthetic response compared with those without this response. . These results suggest that the ‘biologically active area’ predicts the type of peri-prosthetic tissue response. The cytokines IL-1ß, IL-5, IL-10, and GM-CSF are associated with lymphocyte-dominated tissue responses from failed small-diameter MoM THA. Cite this article: Bone Joint J 2015;97-B:917–23


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_4 | Pages 11 - 11
1 Mar 2021
Barcik J Ernst M Balligand M Dlaska CE Drenchev L Todorov S Gueorguiev B Skulev H Zeiter S Epari D Windolf M
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The course of secondary fracture healing typically consists of four major phases including inflammation, soft and hard callus formation, and bone remodeling. Callus formation is promoted by mechanical stimulation, yet little is known about the healing tissue response to strain stimuli over shorter timeframes on hourly and daily basis. The aim of this study was to explore the hourly, daily and weekly variations in bone healing progression and to analyze the short-term response of the repair tissue to well-controlled mechanical stimulation. A system for continuous monitoring of fracture healing was designed for implantation in sheep tibia. The experimental model was adapted from Tufekci et al. 2018 and consisted of 3 mm transverse osteotomy and 30 mm bone defect resulting in an intermediate mobile bone fragment in the tibial shaft. Whereas the distal and proximal parts of the tibia were fixed with external fixator, the mobile fragment was connected to the proximal part via a second, active fixator. A linear actuator embedded in the active fixator moved the mobile fragment axially, thus stimulating mechanically the tissue in the osteotomy gap via well-controlled displacement being independent from the sheep's functional weightbearing. A load sensor was integrated in the active fixation to measure the force acting in the osteotomy gap. During each stimulation cycle the displacement and force magnitudes were recorded to determine in vivo fracture stiffness. Following approval of the local ethics committee, experiments were conducted on four skeletally mature sheep. Starting from the first day after surgery, the daily stimulation protocols consisted of 1000 loading events equally distributed over 12 hours from 9:00 to 21:00 resulting in a single loading event every 44 seconds. No stimulation was performed overnight. One animal had to be excluded due to inconsistencies in the load sensor data. The onset of tissue stiffening was detected around the eleventh day post-op. However, on a daily basis, the stiffness was not steadily increasing, but instead, an abrupt drop was observed in the beginning of the daily stimulations. Following this initial drop, the stiffness increased until the last stimulation cycle of the day. The continuous measurements enabled resolving the tissue response to strain stimuli over hours and days. The presented data contributes to the understanding of the influence of patient activity on daily variations in tissue stiffness and can serve to optimize rehabilitation protocols post fractures


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 42 - 42
11 Apr 2023
Hanetseder D Hruschka V Redl H Presen D
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Mesenchymal stem cells (MSCs) have the potential to repair and regenerate damaged tissues in response to injury, such as fracture or other tissue injury. Bone marrow and adipose tissue are the major sources of MSCs. Previous studies suggested that the regenerative activity of stem cells can be enhanced by exposure to tissue microenvironments. The aim of our project was to investigate whether extracellular matrix (ECM) engineered from human induced pluripotent stem cells-derived mesenchymal-like progenitors (hiPSCs-MPs) can enhance the regenerative potential of human bone marrow mesenchymal stromal cells (hBMSCs). ECM was engineered from hiPSC-MPs. ECM structure and composition were characterized before and after decellularization using immunofluorescence and biochemical assays. hBMSCs were cultured on the engineered ECM, and differentiated into osteogenic, chondrogenic and adipogenic lineages. Growth and differentiation responses were compared to tissue culture plastic controls. Decellularization of ECM resulted in efficient cell elimination, as observed in our previous studies. Cultivation hBMSCs on the ECM in osteogenic medium significantly increased hBMSC growth, collagen deposition and alkaline phosphatase activity. Furthermore, expression of osteogenic genes and matrix mineralization were significantly higher compared to plastic controls. Chondrogenic micromass culture on the ECM significantly increased cell growth and expression of chondrogenic markers, including glycosaminoglycans and collagen type II. Adipogenic differentiation of hBMSCs on the ECM resulted in significantly increased hBMSC growth, but significantly reduced lipid vacuole deposition compared to plastic controls. Together, our studies suggest that BMSCs differentiation into osteogenic and chondrogenic lineages can be enhanced, whereas adipogenic activity is decreased by the culture on engineered ECM. Contribution of specific matrix components and underlying mechanisms need to be further elucidated. Our studies suggest that the three-lineage differentiation of aged BMSCs can be modulated by culture on hiPSC-engineered ECM. Further studies are aimed at scaling-up to three-dimensional ECM constructs for osteochondral tissue regeneration


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_12 | Pages 58 - 58
1 Oct 2019
Mirick GM Sabin A Hansen G Lindgren B Aparicio C Carlson CS Bue M Larsen O Schmidt AH Kyle R Gustilo RB Tsukayama D Bechtold JE
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Introduction. We studied free (= local powder) tobramycin and doxycycline, and controlled release (= local lipid bilayer) doxycycline formulations in a rat model representing a generic joint infection. We . hypothesized. that evidence of infection (quantitative colony forming units (CFU), qualitative SEM, histopathology) (1a) would be reduced with local vs. systemic antibiotic, (1b) any antibiotic would be superior to control (2) there would be a difference among antibiotics, and (3) antibiotic would not be detectable in serum at 4-week euthanasia. Methods. Study groups. included infected and non-infected (1) control, (2) systemic ceftriaxone (daily), (3) local tobramycin, (4) local doxycycline and (5) controlled release doxycycline. With IACUC approval, (10 rats/group; power =0.8), 50-μl, 10×4 CFU Staphylococcus aureus, slowly injecting into distal femoral medullary canal, reliably created joint infection. Antibiotic formulation was introduced locally into cavity and joint, pin was inserted, and tissues closed. After 4-weeks, serum, pin, bone and synovium were obtained. CFU/ml of bone and synovium were quantified using macrotiter method. SEM imaged biofilm on surface of pin, histopathology identified tissue response, liquid chromatography/mass spectrometry measured plasma antibiotic. Kruskal-Wallis one-way ANOVA compared groups. Results. Groups receiving antibiotic reported lower CFU/ml in synovium compared with control (no treatment) group (1b), but there was no difference between systemic, free or controlled antibiotics (1a). Different results with different antibiotics were shown, with free tobramycin reducing CFU/ml to a greater extent than free doxycycline in the synovium (2) (p<0.05). Antibiotic in plasma was nondetectable all groups (3). SEM revealed some biofilm on pin in all groups. . Limitations. include inoculation method, single observation period, administration of only one bacterial and antibiotic dose, and not including pairing local and systemic antibiotic. Conclusion. There was no difference in infection reduction nor detectable antibiotic in serum for any antibiotic formulation, but CFU's in synovium differed based on antibiotic formulation. For any tables or figures, please contact the authors directly


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_2 | Pages 72 - 72
1 Feb 2020
Hall D Garrigues G Blanchard K Shewman E Nicholson G Pourzal R
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Introduction. The combined incidence of anatomic (aTSA) and reverse total shoulder arthroplasties (rTSA) in the US is 90,000 per annum and rising. There has been little attention given to potential long-term complications due to periprosthetic tissue reactions to implant debris. The shoulder has been felt to be relatively immune to these complications due to lower acting loads compared to other joint arthroplasties. In this study, retrieved aTSAs and rTSAs were examined to determine the extent of implant damage and to characterize the nature of the corresponding periprosthetic tissue responses. Methods. TSA components and periprosthetic tissues were retrieved from 23 (eleven aTSA, twelve rTSA). Damage to the implants was characterized using light microscopy. Head/stem taper junction damage was graded 1–4 as minimal, mild, moderate or marked. Damage on polyethylene (PE) and metal bearing surfaces was graded 1–3 (mild, moderate, marked). H&E stained sections of periprosthetic soft tissues were evaluated for the extent and type of cellular response. A semi-quantitative system was used to score (1=rare to 4=marked) the overall number of particle-laden macrophages, foreign body giant cells, lymphocytes, plasma cells, eosinophils, and neutrophils. Implant damage and histopathological patterns were compared between the two TSA groups using the Mann-Whitney and Spearman tests. Results. The PE bearing surfaces of aTSAs were dominated by three-body wear and plastic deformation, whereas the rTSA PE components exhibited mainly polishing and scratching. Metal surface damage occurred in a few cases of both groups. Only one aTSA case exhibited marked taper corrosion. In both groups the primary nature of the inflammatory response was a moderate to marked macrophage response to wear particles (78% of cases). The particle-laden macrophages tended to occur in broad sheets and contained metal, PE, bone cement and suture debris. The extent of macrophage and foreign body giant cell responses was greater in the aTSA group (p≤0.001). Metal particles were seen in 63% of aTSAs and 83% of rTSAs. In the aTSA group, bone cement was seen in all cases and suture was observed in 9 cases, and their presence was larger compared to the rTSA group (p≤0.022). There was no difference in the number of other cell types between the groups. A mild lymphocyte response and chromium-phosphate debris was present within the tissue of the aTSA case with marked corrosion, which may be indicative of an early stage adverse local tissue reaction (ALTR) analog to total hip replacements with taper corrosion. Conclusion. Both groups exhibited a strong macrophage response to a combination of different types of implant debris—PE, metal, bone cement and suture. The prevalence of a marked macrophage response was larger in the aTSA group which may be explained by the larger overall presence of cement and suture within this group. PE particles may differ in size between groups due to different acting wear mechanisms which may also affect the extent of the macrophage response. Although corrosion within modular junctions was overall rare, the presence of one case with marked corrosion shows that taper corrosion and subsequent ALTRs are possible in TSAs. For any figures or tables, please contact authors directly


Objectives. Bioresorbable orthopaedic devices with calcium phosphate (CaP) fillers are commercially available on the assumption that increased calcium (Ca) locally drives new bone formation, but the clinical benefits are unknown. Electron beam (EB) irradiation of polymer devices has been shown to enhance the release of Ca. The aims of this study were to: 1) establish the biological safety of EB surface-modified bioresorbable devices; 2) test the release kinetics of CaP from a polymer device; and 3) establish any subsequent beneficial effects on bone repair in vivo. Methods. ActivaScrew Interference (Bioretec Ltd, Tampere, Finland) and poly(L-lactide-co-glycolide) (PLGA) orthopaedic screws containing 10 wt% β-tricalcium phosphate (β-TCP) underwent EB treatment. In vitro degradation over 36 weeks was investigated by recording mass loss, pH change, and Ca release. Implant performance was investigated in vivo over 36 weeks using a lapine femoral condyle model. Bone growth and osteoclast activity were assessed by histology and enzyme histochemistry. Results. Calcium release doubled in the EB-treated group before returning to a level seen in untreated samples at 28 weeks. Extensive bone growth was observed around the perimeter of all implant types, along with limited osteoclastic activity. No statistically significant differences between comparative groups was identified. Conclusion. The higher than normal dose of EB used for surface modification did not adversely affect tissue response around implants in vivo. Surprisingly, incorporation of β-TCP and the subsequent accelerated release of Ca had no significant effect on in vivo implant performance, calling into question the clinical evidence base for these commercially available devices. Cite this article: I. Palmer, S. A. Clarke, F. J Buchanan. Enhanced release of calcium phosphate additives from bioresorbable orthopaedic devices using irradiation technology is non-beneficial in a rabbit model: An animal study. Bone Joint Res 2019;8:266–274. DOI: 10.1302/2046-3758.86.BJR-2018-0224.R2


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_1 | Pages 103 - 103
1 Feb 2020
Liu S Hall D McCarthy S Chen S Jacobs J Urban R Pourzal R
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Wear and corrosion debris generated from total hip replacements (THR) can cause adverse local tissue reactions (ALTR) or osteolysis, often leading to premature implant failure. The tissue response can be best characterized by histopathological analysis, which accurately determines the presence of cell types, but is limited in the characterization of biochemical changes (e.g. protein conformation alteration). Fourier transform infrared micro-spectroscopy imaging (FTIRI) enables rapid analysis of the chemical structure of biological tissue with a high spatial resolution, and minimal additional sample preparation. The data provides the most information through multivariate method carried out by hierarchical clustering analysis (HCA). It is the goal of this study to demonstrate the beneficial use of this multivariate approach in providing pathologist with biochemical information from cellular and subcellular organization within joint capsule tissue retrieved from THR patients. Joint capsule tissue from 2 retrieved THRs was studied. Case 1: a metal-on-polyethylene THR, and Case 2: a dual modular metal-on-metal THR. Prior to FTIRI analysis, tissue samples were formalin-fixed paraffin-embedded and 5μm thick microtome sectioned samples were prepared and mounted on BaF. 2. discs and deparaffinized. FTIRI data were collected using high-definition transmission mode (pixel size: ∼1.1 μm. 2. ). Hyperspectral images were exported to CytoSpec V2.0.06 for processing and reconstruction into pseudo-color maps based on cluster assignments. Case 1 exhibited a strong presence of lymphocytes and macrophages (Fig. 1a). Since the process of taking second derivatives reduces the half width of the spectral peaks, it increases the sensitivity toward detecting shoulders or second peaks that may not be apparent in the raw spectra (Fig. 1b). Thus, areas occupied by lymphocytes and macrophages can be easily distinguished providing a fast tissue screening method. Here, HCA was able to distinguish macrophages and lymphocytes based on the infrared response, even in areas where both occurred intermixed. (Fig. 1c) The tissue in direct proximity to cells had a slightly altered collagenous structure. Case 1 also exhibited multiple glassy, green particles which can typically observed around THRs that underwent taper corrosion (Fig. 2a). HCA image was able to visualize and distinguish large CrPO. 4. particles, embedded within fibrin exudate rich areas, collagenous tissue without inflammatory cells, and a nearby area with a strong macrophage presence and some finer CrPO. 4. particles (Fig. 2d). Moreover, this method can not only locate macrophages, but distinguish particle-laden macrophages depending the type of particles within the cells. In Case 2 (Fig. 3a), clustering results (Fig. 3 b&c) are consistent with the fact that different particle types are associated with MoM bearing surface wear (Co rich particles), corrosion of the CoCrMo taper junctions (Cr-oxides and –phosphate), fretting of Ti-alloy dual modular tapers (Ti-oxides, Ti alloy particles), and even suture debris, which all occurred in this case. Although details of debris types are not available, specifications are possible by coupling other techniques. The results demonstrate that multivariate FTIRI based spectral histopathology is a powerful tool to characterize the chemical structure and foreign body response within periprosthetic tissue, thus providing insights into the biological impact of different types of implant debris. For any figures or tables, please contact the authors directly


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 10 | Pages 1278 - 1283
1 Oct 2008
Eswaramoorthy V Moonot P Kalairajah Y Biant LC Field RE

We report the clinical and radiological outcome at ten years of 104 primary total hip replacements (100 patients) using the Metasul metal-on-metal bearing. Of these, 52 had a cemented Stuehmer-Weber polyethylene acetabular component with a Metasul bearing and 52 had an uncemented Allofit acetabular component with a Metasul liner. A total of 15 patients (16 hips) died before their follow-up at ten years and three were lost to follow-up. The study group therefore comprised 82 patients (85 hips). The mean Oxford score at ten years was 20.7 (12 to 42). Six of 85 hips required revision surgery. One was performed because of infection, one for aseptic loosening of the acetabular component and four because of unexplained pain. Histological examination showed an aseptic lymphocytic vasculitis associated lesion-type tissue response in two of these. Continued follow-up is advocated in order to monitor the long-term performance of the Metasul bearing and tissue responses to metal debris


The Journal of Bone & Joint Surgery British Volume
Vol. 86-B, Issue 1 | Pages 120 - 125
1 Jan 2004
Nilsson M Wang J Wielanek L Tanner KE Lidgren L

An injectable material consisting of calcium sulphate mixed with hydroxyapatite was investigated as a possible alternative to autograft in the restoration of bone defects. The material was studied both in vitro in simulated body fluid (SBF) and in vivo when implanted in rat muscles and into the proximal tibiae of rabbits. Variation in the strength and weight of the material during ageing in SBF was measured. Tissue response, material resorption and bone ingrowth were studied in the animal models. A good tissue response was observed in both the rat muscles and rabbit tibiae without inflammatory reactions or the presence of fibrous tissue. Ageing in SBF showed that during the first week carbonated hydroxyapatite precipitated on the surfaces of the material and this may enhance bone ingrowth


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 6 | Pages 915 - 919
1 Aug 2002
Bechtold JE Kubic V Søballe K

We have investigated whether the presence of polyethylene (PE) alone is sufficient to cause an aggressive periprosthetic tissue response, or whether certain mechanical interface conditions can allow bone to grow while in the presence of PE. An experimental implant was loaded in the presence and absence of particulate PE under stable and unstable conditions. Bone with a thin, discontinuous fibrous membrane formed in both groups of stable implants, either in the presence or absence of PE. By contrast, a continuous fibrous membrane consistently formed in both groups of unstable implants. The membrane consisted of loose fibrous connective tissue when PE was absent, and dense connective tissue with macrophages and a synovial lining when PE was present. In this model, if the interface was stable, the presence of PE was not sufficient to prevent the formation of bone or to produce a phagocytic tissue response. Only when the interface was unstable did a fibrous membrane form, and only then in the presence of PE


The Journal of Bone & Joint Surgery British Volume
Vol. 80-B, Issue 5 | Pages 888 - 893
1 Sep 1998
Overgaard L Danielsen N Bjursten LM

Little is known about the tissue reactions to various implant materials which coincide with an inflammatory reaction. We used the avridine arthritis rat model to evaluate the tissue response in the synovial, interstitial and subcutaneous tissues after implant insertion. Quantitative immunohistochemistry showed that normal joint synovial tissue is dominated by ED2-positive resident macrophages. Polyethylene implants induced a much stronger foreign-body reaction than titanium implants, as measured by the number of interfacial ED1-positive macrophages. The tissue response to titanium and polyethylene was also vastly different in arthritic synovial tissue compared with control tissue. It is likely that these biomaterials interact differently with inflammatory cells or intermediary compounds. It may be that arthritic synovial tissue produces reactive oxygen intermediates (free radicals) with which titanium has a unique anti-inflammatory interaction in vitro


Bone & Joint Open
Vol. 4, Issue 6 | Pages 408 - 415
1 Jun 2023
Ramkumar PN Shaikh HJF Woo JJ Haeberle HS Pang M Brooks PJ

Aims

The aims of the study were to report for a cohort aged younger than 40 years: 1) indications for HRA; 2) patient-reported outcomes in terms of the modified Harris Hip Score (HHS); 3) dislocation rate; and 4) revision rate.

Methods

This retrospective analysis identified 267 hips from 224 patients who underwent an hip resurfacing arthroplasty (HRA) from a single fellowship-trained surgeon using the direct lateral approach between 2007 and 2019. Inclusion criteria was minimum two-year follow-up, and age younger than 40 years. Patients were followed using a prospectively maintained institutional database.


Bone & Joint Research
Vol. 12, Issue 3 | Pages 155 - 164
1 Mar 2023
McCarty CP Nazif MA Sangiorgio SN Ebramzadeh E Park S

Aims

Taper corrosion has been widely reported to be problematic for modular total hip arthroplasty implants. A simple and systematic method to evaluate taper damage with sufficient resolution is needed. We introduce a semiquantitative grading system for modular femoral tapers to characterize taper corrosion damage.

Methods

After examining a unique collection of retrieved cobalt-chromium (CoCr) taper sleeves (n = 465) using the widely-used Goldberg system, we developed an expanded six-point visual grading system intended to characterize the severity, visible material loss, and absence of direct component contact due to corrosion. Female taper sleeve damage was evaluated by three blinded observers using the Goldberg scoring system and the expanded system. A subset (n = 85) was then re-evaluated following destructive cleaning, using both scoring systems. Material loss for this subset was quantified using metrology and correlated with both scoring systems.


Bone & Joint Research
Vol. 13, Issue 6 | Pages 279 - 293
7 Jun 2024
Morris JL Letson HL McEwen PC Dobson GP

Aims

Adenosine, lidocaine, and Mg2+ (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery.

Methods

Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_5 | Pages 89 - 89
1 Apr 2019
Hall D Pourzal R Wright J McCarthy S Jacobs J Urban R
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Introduction. Little is known about the relationship between head-neck corrosion and its effect on periprosthetic tissues and distant organs in the majority of patients hosting apparently well-functioning devices. We studied the degree and type of taper damage and the histopathologic response in periprosthetic tissue and distant organs. Methods. A total of 50 contemporary THRs (34 primary, 16 revision) retrieved postmortem from 40 patients after 0.4–26 years were studied. Forty-three femoral stems were CoCrMo and 7 were Ti6Al4V. In every case, a CoCrMo-alloy head articulated against a cementless polyethylene cup (19 XLPE and 31 UHMWPE). H&E and IHC sections of the joint pseudocapsules and liver were graded 1–4 for the intensity of various inflammatory cell infiltrates and tissue necrosis. The nature of the tissue response in the joint capsule, liver, spleen, kidneys and lymph nodes was assessed. Wear and corrosion products in the tissues were identified using SEM and EDS. Taper surfaces were graded for corrosion damage using modified Goldberg scoring and examined by SEM to determine the acting corrosion mode. Correlations between damage scores and the histologic variables were generated using the Spearman test. Results. No correlation was seen between taper damage scores and the macrophage response in the joint pseudocapsule. The distribution of corrosion scores for heads and femoral trunnions is shown in Figure 1. Moderate or severe corrosion of the head and/or trunnion was present in 9 hips (8 CoCr/CoCr and 1 CoCr/TiAlV). One patient with bilateral hips had local ALVAL-like lymphocyte-dominated tissue reactions (Figure 2) and mild focal lymphocytic infiltrates in the liver and kidneys (Figure 3). This was associated with severe intergranular corrosion of the CoCrMo trunnion and column damage on the head taper. Particle-laden macrophages in pseudocapsules were significantly correlated with liver macrophages (r=.382, p=0.012) and liver lymphocytes (r=.367, p=0.013). Pseudocapsule macrophage responses to metallic and/or polyethylene wear particles ranged widely from minimal to marked. Focal tissue necrosis was related to high concentrations of particulate wear debris. A minimal number of metallic particle-laden macrophages were also detected in the liver and spleen; and macrophage granulomas were present in para-aortic lymph nodes, especially in revision cases. DISCUSSION. The generation of metal ions and particulates at corroded CoCrMo heads and CoCrMo or Ti6Al4V trunnions was a significant contributor to the presence of perivascular lymphocytes within the joint pseudocapsule, with 1 patient showing a histologic pattern consistent with ALVAL. Patient factors and the rate of corrosion are among variables influencing whether an ALVAL-type reaction will develop and whether or not it will become symptomatic. Macrophages in the joint pseudocapsules were positively correlated with inflammatory cells in the liver. In this study, the intensity of inflammatory infiltrates in distant organs was mild. However, several cases of organ dysfunction have been reported in association with catastrophic wear of CoCrMo components. It continues to be essential to minimize the generation of metal ions and particulates and to improve strategies for identifying and managing patients exposed to high levels of degradation products. For any figures or tables, please contact the authors directly


Bone & Joint Research
Vol. 12, Issue 10 | Pages 657 - 666
17 Oct 2023
Sung J Barratt KR Pederson SM Chenu C Reichert I Atkins GJ Anderson PH Smitham PJ

Aims

Impaired fracture repair in patients with type 2 diabetes mellitus (T2DM) is not fully understood. In this study, we aimed to characterize the local changes in gene expression (GE) associated with diabetic fracture. We used an unbiased approach to compare GE in the fracture callus of Zucker diabetic fatty (ZDF) rats relative to wild-type (WT) littermates at three weeks following femoral osteotomy.

Methods

Zucker rats, WT and homozygous for leptin receptor mutation (ZDF), were fed a moderately high-fat diet to induce T2DM only in the ZDF animals. At ten weeks of age, open femoral fractures were simulated using a unilateral osteotomy stabilized with an external fixator. At three weeks post-surgery, the fractured femur from each animal was retrieved for analysis. Callus formation and the extent of healing were assessed by radiograph and histology. Bone tissue was processed for total RNA extraction and messenger RNA (mRNA) sequencing (mRNA-Seq).


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_5 | Pages 58 - 58
1 Feb 2016
Hacihaliloglu I Rohling R Abolmaesumi P
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A challenging problem in ultrasound based orthopaedic surgery is the identification and interpretation of bone surfaces. Recently we have proposed a new fully automatic ultrasound bone surface enhancement filter in the context of spine interventions. The method is based on the use of a Gradient Energy Tensor filter to construct a new feature enhancement metric, which we call the Local Phase Tensor. The goal of this study is to provide further improvements to the proposed filtering method by incorporating a-priori knowledge about the physics of ultrasound imaging and salient grouping of enhanced bone features. Typical ultrasound scan of the spine, there is a large soft tissue interface present close to the transducer surface with high intensity values similar to those of the bone anatomy response. Typical ultrasound image segmentation or enhancement methods will be affected by this thick soft tissue response. In order to weaken this soft tissue interface we calculate a new transmission map where features deeper in the ultrasound image have higher transmission values and shallow features have lower transmission values. The calculation of this new US transmission/attenuation map allows the proposed image enhancement method to mask out erroneous regions, such as the soft tissue interface, and improve the accuracy and robustness of the spine surface enhancement. The masked US images were used as an input to the LPT image enhancement method. In order to provide a more compact spine surface representation and further reduce the typical US imaging artifacts and soft tissue interfaces we calculate saliency Local Phase Tensor features. The saliency images are computed using Difference of Gaussian filters. Qualitative results, obtained from in vivo clinical scans, show a strong correspondence between enhanced features and the actual bone surfaces present in the ultrasound scans. Future work will include the extension of the proposed method to 3D and validation of the method in the context of intra-operative ultrasound image registration in CAOS applications


Bone & Joint 360
Vol. 11, Issue 2 | Pages 15 - 18
1 Apr 2022