Adverse Tissue Research Articles

The use of the RegJoint™ implant for base of thumb osteoarthritis: Results with a minimum follow-up of 2 years

The RegJoint™ (Scaffdex Oy, Finland) implant is a bio-absorbable poly-L/D-lactide implant which acts as a temporary support in resected joint spaces. It can be used in base of thumb surgery as a spacer to prevent first metacarpal subsidence. However, high rates of adverse tissue reactions and bone osteolysis have been reported recently by one group. The objective of this study was to investigate the outcome of patients treated in our institution with this implant. Patients underwent a postoperative clinical and radiological assessment. The QuickDASH questionnaire, Patient Evaluation Measure (PEM) and a visual analogue scale for pain assessment were used. Grip strength, key pinch, pinch strength, thumb palmar and radial abduction and opposition were measured. Trapeziometacarpal height was used to evaluate thumb shortening compared with the preoperative value. Periprosthetic bone-erosion of the trapezium and metacarpal were measured. Subluxation of the joint was evaluated by measuring the step-off between the radial edge of the trapezium and the base of the first metacarpal bone. Twenty-two patients from 2013–2016 were included. There were no postoperative wound complications. There was no significant difference in grip strength, key pinch or pinch between the operated and the contralateral hand. There was no significant difference in the trapeziometacarpal height, trapezial height or the degree of subluxation pre-or post-operatively. Contrary to recent reports, we did not find any adverse soft tissue reactions or significant bone erosion. There was no significant change in hand function. We consider the RegJoint™ a useful adjunct in the management of a select cohort of patients with base of thumb arthritis.

Recent Progress on Mg- and Zn-Based Alloys for Biodegradable Vascular Stent Applications

Currently, biodegradable metals for implantation applications are widely investigated to replace biodegradable polymeric implantations, which may cause inflammatory or adverse local tissue reactions. Amongst these metals, magnesium (Mg) and zinc (Zn) alloys with good biocompatibility, mechanical properties, and corrosion resistance are being widely investigated. In this review, the criteria for biodegradable vascular stents, and the advantages and limitations of biodegradable Mg and Zn vascular stents, are summarized and evaluated. By summarizing and discussing recent research on Mg- and Zn-based alloys used as biodegradable vascular stents, this review considered many alloys that can potentially serve as biodegradable vascular stents and suggests future research directions for the development of Mg- and Zn-based alloys as biodegradable metal stents.

Wear particles induce a new macrophage phenotype with the potential to accelerate material corrosion within total hip replacement interfaces

Evidence that macrophages can play a role in accelerating corrosion in CoCrMo alloy in total hip replacement (THR) interfaces leads to questions regarding the underlying cellular mechanisms and immunological responses. Hence, we evaluated the role of macrophages in corrosion processes using the cell culture supernatant from different conditions and the effect of wear particles on macrophage dynamics. Monocytes were exposed to CoCrMo wear particles and their effect on macrophage differentiation was investigated by comparisons with M1 and M2 macrophage differentiation. Corrosion associated macrophages (MCA macrophages) exhibited upregulation of TNF-α, iNOS, STAT-6, and PPARG and down-regulation of CD86 and ARG, when compared to M1 and M2 macrophages. MCA cells also secreted higher levels of IL-8, IL-1β, IL-6, IL-10, TNF-α, and IL-12p70 than M1 macrophages and/or M2 macrophages. Our findings revealed variation in macrophage phenotype (MCA) induced by CoCrMo wear particles in generating a chemical environment that induces cell-accelerated corrosion of CoCrMo alloy at THR modular interfaces. Statement of SignificanceFretting wear and corrosion within the implant's modular taper junction are prominent causes of implant failure, as they promote the release of corrosion products and subsequent development of adverse local tissue reactions. Being a multifactorial process, several in vitro models have been developed to recreate the in vivo corrosion process, often summarized as mechanically-assisted crevice corrosion. Considering the excellent corrosion properties of CoCrMo alloy, the severity of chemically-generated damage observed at the modular interface has been surprising and poorly understood. The aim of the current study is to provide a better understanding of macrophages and their plasticity at the THR taper interface when they encounter wear debris from CoCrMo alloy. This is a preliminary study along the path towards determining the mechanism(s) of CAC.

The CD73/Ado System-A New Player in RT Induced Adverse Late Effects.

Radiotherapy (RT) is a central component of standard treatment for many cancer patients. RT alone or in multimodal treatment strategies has a documented contribution to enhanced local control and overall survival of cancer patients, and cancer cure. Clinical RT aims at maximizing tumor control, while minimizing the risk for RT-induced adverse late effects. However, acute and late toxicities of IR in normal tissues are still important biological barriers to successful RT: While curative RT may not be tolerable, sub-optimal tolerable RT doses will lead to fatal outcomes by local recurrence or metastatic disease, even when accepting adverse normal tissue effects that decrease the quality of life of irradiated cancer patients. Technical improvements in treatment planning and the increasing use of particle therapy have allowed for a more accurate delivery of IR to the tumor volume and have thereby helped to improve the safety profile of RT for many solid tumors. With these technical and physical strategies reaching their natural limits, current research for improving the therapeutic gain of RT focuses on innovative biological concepts that either selectively limit the adverse effects of RT in normal tissues without protecting the tumor or specifically increase the radiosensitivity of the tumor tissue without enhancing the risk of normal tissue complications. The biology-based optimization of RT requires the identification of biological factors that are linked to differential radiosensitivity of normal or tumor tissues, and are amenable to therapeutic targeting. Extracellular adenosine is an endogenous mediator critical to the maintenance of homeostasis in various tissues. Adenosine is either released from stressed or injured cells or generated from extracellular adenine nucleotides by the concerted action of the ectoenzymes ectoapyrase (CD39) and 5′ ectonucleotidase (NT5E, CD73) that catabolize ATP to adenosine. Recent work revealed a role of the immunoregulatory CD73/adenosine system in radiation-induced fibrotic disease in normal tissues suggesting a potential use as novel therapeutic target for normal tissue protection. The present review summarizes relevant findings on the pathologic roles of CD73 and adenosine in radiation-induced fibrosis in different organs (lung, skin, gut, and kidney) that have been obtained in preclinical models and proposes a refined model of radiation-induced normal tissue toxicity including the disease-promoting effects of radiation-induced activation of CD73/adenosine signaling in the irradiated tissue environment. However, expression and activity of the CD73/adenosine system in the tumor environment has also been linked to increased tumor growth and tumor immune escape, at least in preclinical models. Therefore, we will discuss the use of pharmacologic inhibition of CD73/adenosine-signaling as a promising strategy for improving the therapeutic gain of RT by targeting both, malignant tumor growth and adverse late effects of RT with a focus on fibrotic disease. The consideration of the therapeutic window is particularly important in view of the increasing use of RT in combination with various molecularly targeted agents and immunotherapy to enhance the tumor radiation response, as such combinations may result in increased or novel toxicities, as well as the increasing number of cancer survivors.

Innovative tailor made dextran based membranes with excellent non-inflammatory response: In vivo assessment.

In this work, dextran based membranes with potential to be used as implantable devices in Tissue Engineering and Regenerative Medicine (TERM) were prepared by a straightforward strategy. Briefly, two polymers approved by the Food and Drug Administration, viz. dextran and poly(ε-caprolactone) (PCL) were functionalized with methacrylate moieties, and subjected to photocrosslinking. Employing different weight ratios of each polymer in the formulations allowed to obtain transparent membranes with tunable physicochemical properties and low adverse host tissue response. Independently of the material, all formulations have shown to be thermally stable up to 300 °C whilst variations in the polymer ratio resulted in membranes with different glass transition temperatures (Tg) and flexibility. The swelling capacity ranged from 50% to 200%. On the other hand, in vitro hydrolytic degradation did not show to be material-dependent and all membranes maintained their structural integrity for more than 30 days, losing only 8-12% of their initial weight. Preliminary in vitro biological tests did not show any cytotoxic effect on seeded human dental pulp stem cells (hDPSCs), suggesting that, in general, all membranes are capable of supporting cell adhesion and viability. The in vivo biocompatibility of membranes implanted subcutaneously in rats' dorsum indicate that M100/0 (100%wt dextran) and M25/75 (25 %wt dextran) formulations can be classified as "slight-irritant" and "non-irritant", respectively. From the histological analysis performed on the main tissue organs it was not possible to detect any signs of fibrosis or necrosis thereby excluding the presence of toxic degradation by-products deposited or accumulated in these tissues. In combination, these results suggest that the newly developed formulations hold great potential as engineered devices for biomedical applications, where the biological response of cells and tissues are greatly dependent on the physical and chemical cues provided by the substrate.

Validation of revision data for total hip and knee replacements undertaken at a high volume orthopaedic centre against data held on the National Joint Registry

BackgroundWith over 2.35 million records, the National Joint Registry (NJR) is the largest arthroplasty registry in the world. It provides a powerful tool to monitor implant survivorship and influence different surgical strategies. To date, little work has been undertaken to investigate the validity of the ‘Reason for Revision’ recorded in Consultant Outcome Reports on the NJR.MethodsThe NJR was queried to identify all revisions on the THR performed at a single centre over an 11-year period. Review and validation of ‘Reason for Revision’ for each case was undertaken using radiological imaging studies, pathology, histology, microbiology and electronic medical records.ResultsOf the 22,046 primary total hip replacements (THR) and total knee replacements (TKR) undertaken by 23 surgeons at our hospital, over an 11-year period, 1.35% (297) were subsequently reported to the NJR as revised. Discrepancies in reporting to the NJR were identified for 41 cases (25.63%) for THR and 28 (20.40%) cases for TKR. Revision for infection was under-reported for both THR and TKR by 1.88% and 3.65% respectively. Reporting of adverse soft tissue reaction to particulate debris for THR was unreported by 11%. Progressive arthritis following a TKR was unreported by 6.56%. All the cases reported as ‘other’ (8.75% for THRs and 3.65% for TKRs) were reclassified to the most appropriate ‘reason for revision’ category. The ‘reason for revision’ data is recorded to the NJR with findings at the time of surgery. It is some days before microbiology and histology reports become available and source data is not always updated.ConclusionIf an average of 23% wrong data entry at a highly organised institution is replicated throughout the UK, a formal process to validate primary and revision data submitted to the NJR should be considered. Local scrutiny, review and validation of revision data are all vital to optimise the value of the NJR. Accurate data recorded to the NJR is imperative to provide safe and effective improvements in orthopaedic surgery.

Individual Radiosensitivity in Oncological Patients: Linking Adverse Normal Tissue Reactions and Genetic Features.

Introduction: Adverse effects of radiotherapy (RT) significantly affect patient's quality of life (QOL). The possibility to identify patient-related factors that are associated with individual radiosensitivity would optimize adjuvant RT treatment, limiting the severity of normal tissue reactions, and improving patient's QOL. In this study, we analyzed the relationships between genetic features and toxicity grading manifested by RT patients looking for possible biomarkers of individual radiosensitivity.Methods: Early radiation toxicity was evaluated on 143 oncological patients according to the Common Terminology Criteria for Adverse Events (CTCAE). An individual radiosensitivity (IRS) index defining four classes of radiosensitivity (highly radiosensitive, radiosensitive, normal, and radioresistant) was determined by a G2-chromosomal assay on ex vivo irradiated, patient-derived blood samples. The expression level of 15 radioresponsive genes has been measured by quantitative real-time PCR at 24 h after the first RT fraction, in blood samples of a subset of 57 patients, representing the four IRS classes.Results: By applying univariate and multivariate statistical analyses, we found that fatigue was significantly associated with IRS index. Interestingly, associations were detected between clinical radiation toxicity and gene expression (ATM, CDKN1A, FDXR, SESN1, XPC, ZMAT3, and BCL2/BAX ratio) and between IRS index and gene expression (BBC3, FDXR, GADD45A, and BCL2/BAX).Conclusions: In this prospective cohort study we found that associations exist between normal tissue reactions and genetic features in RT-treated patients. Overall, our findings can contribute to the identification of biological markers to predict RT toxicity in normal tissues.

Midterm outcomes of total hip arthroplasty with a modular Birmingham head.

Birmingham Hip Resurfacing (BHR) implants may be combined with a conventional femoral stem to create a modular metal-on-metal total hip arthroplasty (BHR MoM THA). There is little outcome data regarding this construct. This study examines midterm outcomes of BHR MoM THA compared to oxidised zirconium total hip arthroplasty (THA). A retrospective institutional review identified all patients receiving BHR MoM THA between April 2005 and February 2011 and a matched control cohort of zirconium THA patients. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Harris Hip Score (HHS), and SF-12 Health status scores were obtained. Revisions and complications were collected from clinical records. Radiographs were assessed for evidence of component malposition, loosening, osteolysis, or heterotopic ossification. 63 modular BHR MoM THA were identified in 61 patients (36 with BHR cups, 27 with R3 cups) and 63 zirconium THA in 58 matched controls. Mean follow-up was 58 months. 14 BHR MoM THA hips (22.2%) were revised (4 infections, 1 dislocation, 9 soft tissue reactions) compared to 3 (4.8%) zirconium THA (all infections). At latest follow-up, 18.4% of surviving BHR MoM THA hips were painful compared to 0.5% of zirconium THA controls (p < 0.001). WOMAC, HHS, and SF-12 did not differ significantly between surviving members of the 2 groups. BHR MoM THA demonstrated a high revision rate, largely for adverse local soft tissue reaction and pain. Among those not revised, many reported some residual pain despite similar quality of life measures to those who received zirconium THA.

The influence of protein concentration, temperature and cathodic polarization on the surface status of CoCrMo biomedical grade alloys

CoCrMo alloys have been widely used in hip replacements. On the one hand they have exhibited excellent long-term survival rates, but recently high failure rates have been observed, associated with adverse local tissue reactions. It is still a puzzle why CoCrMo alloys sometimes work very well, while at the other times the failure rate is unacceptably high. The current work aims to investigate the influence of protein adsorption on the oxide layer properties and consequently on corrosion behaviour of CoCrMo biomedical grade alloys in different surface and media conditions. Electrochemical Impedance Spectroscopy (EIS), SEM and AFM were employed to characterise the surfaces. TEM was also used to reveal the subsurface chemical composition. The results showed a significant drop in the resistance of the oxide layer on the surfaces after some cathodic potential polarization. It was also shown that higher protein content and temperature reduced the oxide layer/metal surface interface resistivity. EDX quantitative chemical composition spot analysis of the subsurface after cathodic polarization showed a depletion of chromium in the outermost layer. AFM imaging and peak-force quantitative nanomechanical mapping QNM revealed lower adhesion forces for a relatively thick proteinaceous adsorbed layer on the surface after high cathodic polarization in particular at 50 °C.

Creating an antibacterial surface on beta TNZT alloys for hip implant applications by laser nitriding

The National Joint Registry reported that the main causes for hip implant revision surgery include aseptic loosening, infection and adverse soft tissue reaction to particulate debris. There is a great need to improve the implant properties which can be achieved through a combined solution of beta titanium alloy (TNZT) with low elastic modulus and laser surface nitriding to improve mechanical properties and biological response. While titanium nitride (TiN) possesses good biocompatibility and remarkable antibacterial properties; its effectiveness as a coating on Ti-35Nb-7Zr-6Ta has not been investigated in relation to stem cell response and antibacterial capability. TNZT surfaces were laser-nitrided in incremental laser power, specifically 35, 40 and 45 W. Investigation included surface roughness and topography in microscale (WLI and SEM), microstructure (XRD) and wettability (water contact angle). Biological studies of the laser-nitrided surfaces included in vitro culture for 24 h using mesenchymal stem cell (MSC) fluorescence staining and Staphylococcus aureus (S. aureus) Live/Dead staining. Sample groups consisted of control base metal (BM), laser-nitrided at 35 W (LT35), 40 W (LT40) and 45 W (LT45). Results revealed that laser nitriding generates significantly rougher surfaces (Ra value of BM was 199.3 nm, LT35 was 722.8 nm, LT40 was 458.4 nm and LT45 was 1180.2 nm) with distinctive surface features (Rsk < 0 and Rku > 3). Surfaces after laser nitriding, regardless of laser power, can be tailored to become hydrophilic (27.1–34.2°). Fibre laser nitriding can be used to create antibacterial surface patterns on TNZT in a high power regime. A laser power of 45 W proved to be the most effective in this study, creating an overlapping crescent shape which becomes more obvious with increasing power. To summarise, laser-nitrided surfaces led to a significant antibacterial effect but offered no particular advantage to MSC response.

Diagnosis and Management of Adverse Reactions to Metal Debris

Modern total hip arthroplasty implants have incorporated modularity into their designs, providing the benefits of intraoperative flexibility and the ability to exchange the femoral heads in the future if necessary. However, this feature has unfortunately predisposed patients to the effects of corrosion, potentially resulting in adverse local tissue reactions (ALTR) and even systemic effects. A thorough understanding of the science of corrosion is important for the treating surgeon so that they can understand the underlying pathology, quickly diagnose the condition of ALTR, and risk stratify their patients to determine the best method of treatment. Revision surgery is not always necessary in cases of trunnionosis or ALTR, but the results of revision surgery are generally favorable.

Radiographic evaluation of hip resurfacing: the role of x-rays in the diagnosis of a problematic resurfaced hip.

Hip resurfacing (HRA) requires a new standardised radiographic evaluation protocol. Evaluation of acetabular components is similar to total hip arthroplasty (THA) but femoral components require different criteria. This study evaluates the efficacy of a new femoral zonal system for radiographic HRA assessment in identifying clinical problems. A new proximal femoral zonal system divides implant-cement-bone interfaces at head and neck into 7 DeSmet zones. 611 in situ and 100 revised HRA were assessed for component positioning, borderline findings (reactive lines, cortical thickening, cancellous condensation) or sinister findings (lucent lines, bone resorption, osteolysis). Findings were correlated with gender, size, implant survival, clinical scores, metal ions, and adverse soft tissue reactions (ALTR). Radiological changes were found in 265 hips (37.3%), 154 sinister (21.7%) and 111 borderline (15.6%). 84% of revisions had sinister findings versus 11.4% of in situ HRA (p < 0.001). The mean number of abnormal acetabular and femoral zones was 3.3 in revised compared to 0.6 in situ HRA (p < 0.001). Sinister findings were associated with female gender, lower clinical scores, smaller sizes or ASR design (all: p < 0.001). Metal ions were higher with sinister (p < 0.001) and borderline (p < 0.01) findings compared to normal radiographs. Pathological findings in ⩾4 zones had a sensitivity of 50% and specificity of 94.2% (AUC = 0.898) in detecting hips with ALTR (odds ratio = 49). In order to accurately evaluate progressive radiographic changes in HRA, specific zones have been established around the femoral component. There was a high correlation between radiographic findings and outcome measures. 84% of problematic hips and 90.4% of proven ALTR had sinister changes.

Revision of a dual-modular stem in patients with adverse tissue reaction.

Dual-modular femoral components with exchangeable cobalt-chrome neck segments have had higher than expected failure rates due to corrosion and adverse local tissue reaction (ALTR). Complications, survival rates and early clinical outcomes of revision surgery for the treatment of corrosion and ALTR as a result of these implants are underreported. We identified 44 cases of revision THA for corrosion and ALTR resulting from the same dual modular stem. All revision procedures were performed using a modular tapered fluted titanium stem, ceramic heads and highly cross-linked polyethylene. Complications included: dislocation, infection, reoperation, and chronic pain. Mean Harris Hip Score was 84 following revision surgery. Patients undergoing revision surgery for ALTR related to this prosthesis should be aware of the risk of postoperative dislocation and other complications and the potential long-term risk of some chronic pain.

Abstract 520: Cavin-2/SDPR in Cardiac Fibroblasts Modulates TGF-β/Smad Signaling and Promotes Pressure Overload-induced Fibrosis

Introduction: Heart failure (HF) is a debilitating disease associated with high morbidity and mortality. The high mortality rate reflects the inadequacy of modern therapy and calls for new treatments. A major cause of HF is the adverse tissue remodeling with fibrosis. Excessive extracellular matrix (ECM) turnover is involved in the poor outcome. Resident fibroblasts are responsible for cardiac fibrosis on pressure-overload heart failure. Caveolins and Cavins are known as caveolar-related proteins. Caveolin-1 inhibits TGF-β1-induced fibrosis in the previous reports. Although Cavin-2/Serum deprivation response protein (SDPR), which is one of the caveolar-relatedproteins, is also abundant in fibroblasts, the role of Cavin-2 in cardiac fibrosis and function remains unknown. Methods and Results: To clarify the role of Cavin-2 in the cardiac fibroblasts in the pressure-overloadedheart, we performed transverse aortic constriction (TAC) operation on SDPR flox/flox mice and fibroblast-specific Cavin-2 cKO mice (Postin Cre ; SDPR flox/flox ). Four weeks after TAC, left ventricular fractionalshortening (LVFS) was preservedwith a significant reduction of cardiac fibrosis in PostinCre; SDPRflox/flox mice. Fibrosis-associated mRNA expressions ( Col1a1 , Ctgf , Col3 ), α1 type I collagen deposition, and αSMA-positive cells were also reducedin the hearts of Cavin-2 cKO mice after TAC. Trans-differentiation of fibroblasts into activated myofibroblasts is a defining feature of fibrosis. Myofibroblasts express α-smooth muscle actin (αSMA) and secrete ECM proteins via Smad signaling. In mouse embryonic fibroblasts (MEFs),Cavin-2 deficiency reduced the levels of αSMA protein and fibrosis-associated mRNA expressions by TGF-β1 stimulation. Furthermore, TGF-β1-induced Smad2 phosphorylation was attenuatedin Cavin-2 KO MEFs compared to WT MEFs. On the other hand, adenovirus-mediated Cavin-2 overexpression significantly increased αSMA and the fibrosis-associated mRNA expressions. Conclusions: Our observations suggest that Cavin-2 contributes to the development of cardiac fibrosis through the differentiation from fibroblasts into myofibroblasts via TGF-β/Smad signaling. Cavin-2 may be a novel therapeutic target for cardiac fibrosis.

Mechanisms of Adverse Local Tissue Reactions to Hip Implants.

Adverse Local Tissue Reactions (ALTRs) are one of the main causes of hip implant failures. Although the metal release from the implants is considered as a main etiology, the mechanisms, and the roles of the released products are topics of ongoing research. The alloys used in the hip implants are considered biocompatible and show negligible corrosion in the body environment under static conditions. However, modularity and its associated mechanically assisted corrosion have been shown to release metal species into the body fluids. ALTRs associated with metal release have been observed in hip implants with metal-on-metal articulation initially, and later with metal-on-polyethylene articulation, the most commonly used design in current hip replacement. The etiological factors in ALTRs have been the topics of many studies. One commonly accepted theory is that the interactions between the metal species and body proteins and cells generate a delayed type IV hypersensitivity reaction leading to ALTRs. However, lymphocyte reactions are not always observed in ALTRS, and the molecular mechanisms have not been clearly demonstrated. A more accepted mechanism is that cell damage generated by metal ions may trigger the secretion of cytokines leading to the inflammatory reactions observed in ALTRs. In this inflammatory environment, some patients would develop hypersensitivity that is associated with poor outcomes. Concerns over ALTRS have brought significant impact to both the clinical selection and development of hip implants. This review is focused on the mechanisms of ALTRs, specifically, the metal release process and the roles of the metal species released in the etiology and pathogenesis of the disease. Hopefully, our presentation and discussion of this biological process from a material perspective could improve our current understanding on the ALTRs and provide useful guidance in developing preventive solutions.

Genipin and EDC crosslinking of extracellular matrix hydrogel derived from human umbilical cord for neural tissue repair

Extracellular matrix (ECM) hydrogels, produced by tissue decellularization are natural injectable materials suitable for neural tissue repair. However, the rapid biodegradation of these materials may disrupt neural tissue reconstruction in vivo. The aim of this study was to improve the stability of the previously described ECM hydrogel derived from human umbilical cord using genipin and N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC), crosslinking at concentration of 0.5–10 mM. The hydrogels, crosslinked by genipin (ECM/G) or EDC (ECM/D), were evaluated in vitro in terms of their mechanical properties, degradation stability and biocompatibility. ECM/G, unlike ECM/D, crosslinked hydrogels revealed improved rheological properties when compared to uncrosslinked ECM. Both ECM/G and ECM/D slowed down the gelation time and increased the resistance against in vitro enzymatic degradation, while genipin crosslinking was more effective than EDC. Crosslinkers concentration of 1 mM enhanced the in vitro bio-stability of both ECM/G and ECM/D without affecting mesenchymal stem cell proliferation, axonal sprouting or neural stem cell growth and differentiation. Moreover, when injected into cortical photochemical lesion, genipin allowed in situ gelation and improved the retention of ECM for up to 2 weeks without any adverse tissue response or enhanced inflammatory reaction. In summary, we demonstrated that genipin, rather than EDC, improved the bio-stability of injectable ECM hydrogel in biocompatible concentration, and that ECM/G has potential as a scaffold for neural tissue application.

In vitro and preclinical characterisation of compressed, macro-porous and collagen coated poly-ε-caprolactone electro-spun scaffolds

Low in macro-porosity electro-spun scaffolds are often associated with foreign body response, whilst macro-porous electro-spun scaffolds have low mechanical integrity. Herein, compressed, macro-porous and collagen (bovine Achilles tendon and human recombinant) coated electro-spun poly-ε-caprolactone scaffolds were developed and their biomechanical, in vitro and in vivo properties were assessed. Collagen coating, independently of the source, did not significantly affect the biomechanical properties of the scaffolds. Although no significant difference in cell viability was observed between the groups, collagen coated scaffolds induced significantly higher DNA concentration. In vivo, no signs of adverse tissue effect were observed in any of the groups and all groups appeared to equally integrate into the subcutaneous tissue. It is evidenced that macro-porous poly-ε-caprolactone electro-spun meshes with adequate mechanical properties and acceptable host response can be developed for biomedical applications.

Registry study on failure incidence in 1,127 revised hip implants with stem trunnion re-use after 10 years of follow-up: limited influence of an adapter sleeve

Background and purpose — Little is known about the role of retained trunnions in revision hip arthroplasties, i.e., when only the femoral head is substituted. Wear (fretting corrosion) and ceramic head fractures are 2 poorly understood concerns related to use, and the role of adapter sleeves has not been defined. In this registry study we assessed the influence of sleeve interposition on re-revision rates in revision hip arthroplasties with retained stems. Confounding factors (demographics, implant-related features) and failures were also analyzed.Patients and methods — We conducted a registry study on 1,127 revised implants (retained trunnion and head exchange). In 26% of implants an adapter sleeve was interposed; in 74% no adapter sleeve was implanted. Demographic and implant-related features were investigated including a descriptive analysis of failures.Results — The mean follow-up of revised implants with and without the use of an adapter sleeve was 3.3 and 5.1 years, respectively. The implant survival without an adapter sleeve was significantly higher, 98.4% (95% CI 96.9–99.8) vs. 95.2% (CI 93.2–96.6) with an adapter sleeve at 5 years. No re-revisions due to adverse local tissue reactions or ceramic head fractures were reported. In order to overcome the different distribution of head materials and head sizes in the two cohorts, only Delta balls were investigated.Interpretation — Adapter sleeve interposition had a minor influence on the revision rates. No adverse local tissue reactions or head fractures occurred.

Radiological Imaging Evaluation of the Failing Total Hip Replacement.

Total hip replacements (THR) have been performed in the UK from the 1960s and since then we have seen surgical techniques, the design of implants, and imaging modalities rapidly develop. This paper will aim to review the different complications and imaging appearance which help to evaluate each problem. As for all investigations for bone and joints, a radiograph is the first imaging to be performed for any patient with a THR and can detect a majority of complications. CT is relatively low-cost, simple to perform and easily available making it an excellent tool to supplement radiographs when trying to evaluate a hip prosthesis. Single photon emission computed tomography with CT (SPECT-CT) is an emerging modality which has shown to combine the sensitivity that bone scintigraphy offers with the high specificity of CT. SPECT imaging also has the advantage of showing the bone's metabolic activity and is less prone to metal artifact than Magnetic resonance imaging (MRI). MRI has evolved to become an important diagnostic tool for the evaluation of THR in the post-operative period. Optimized pulse sequences and metal artifact reduction techniques have made MRI a useful tool in diagnosis of soft tissue abnormalities and is particularly useful in identifying adverse local tissue reactions in metal on metal implants. CT and MRI are accurate in identifying the diagnosis of most causes of THR complications except infection. Research confirms that leukocyte-marrow scintigraphy is the modality of choice for accurately diagnosing prosthetic joint infection and reassures us of its superiority over other nuclear medicine imaging. However, due to the limited availability and increased costs when performing leukocyte-marrow scintigraphy, CT and SPECT-CT would be a more preferred option when suspecting prosthesis infection. Ultrasound (US) has a limited role in the assessment of most THR complications but can be useful to identify peri-prosthetic fluid collections and the presence of soft tissue sinus tracts. Being aware of the imaging modalities that are available to orthopedic surgeons, and discussing these challenging cases with specialist radiologists will enable optimal management of THR complications.

Mechanical and numerical characterization of ceramic femoral components for hip resurfacing arthroplasty.

Hip resurfacing arthroplasty may have distinct advantages for young and active patients, but large metal-on-metal bearings can be associated with increased wear, adverse tissue reactions and higher rate of implant loosening. Ceramic wear couples are a commonly used alternative to metals and therefore might be an alternative for hip resurfacing arthroplastys. The aim of this study was to evaluate the mechanical strength of femoral components made of an alumina-toughened zirconia composite by means of experimental testing and finite element analysis. For the mechanical characterization, ceramic femoral components (Ø: 48 mm) were tested under compression loading experimentally until fracture occurred or a maximum load of 85 kN was obtained. The femoral components were either loaded against a ceramic cup or a copper ring (outer diameter Ø: 7.0 mm). In addition, the complex geometry of the ceramic femoral component was simplified, and only the stem was loaded in a cantilever test until fracture. In addition, the fracture tests were numerically simulated to investigate the influence of additional loading conditions and geometric parameters, which were not experimentally tested. The experimental data were used for validation of the finite element analysis. None of the tested ceramic femoral components fractured at a compression load of 85 kN when they were loaded against a ceramic cup at an inclination angle of 45°. When the femoral components were loaded against a copper ring, the femoral components fractured at 29.9 kN at a testing angle of 45°. The fracture load was reduced when an angle of 30° and increased when an angle of 60° was simulated. Using an experimental cantilever test, the stem of the femoral component fractured at 1124.0 N. When the stem length was increased or the diameter was reduced by 10% in the finite element analysis, the fracture load was reduced. Decreasing the length or increasing the diameter led to an increase of the fracture load. The strongest influence was found for the reduction of the transition radius of the stem, with a decrease of the fracture load up to 27.2%. The analyzed femoral components made of alumina-toughened zirconia (ATZ) showed sufficient mechanical capability to withstand high loadings during unfavorable loading conditions. However, further biomechanical and tribological investigations are required before clinical application.