Adverse Tissue Research Articles

In vivo behavior of biomicroconcretes based on α-tricalcium phosphate and hybrid hydroxyapatite/chitosan granules and sodium alginate.

The current studies provide insights into how predictions based on results of physicochemical and in vitro tests are consistent with the results of in vivo studies. The new biomicroconcrete type materials were obtained by mixing the solid phase, composed of hybrid hydroxyapatite/chitosan granules and highly reactive α-tricalcium phosphate powder, used as the setting agent. This approach guaranteed a good adhesion of the continuous cement phase to the surface of granules. It has been demonstrated that developed biomicroconcretes are surgically handy, possessed favorable physicochemical and biological properties and can be considered as effective bone implant material. The hierarchical porosity and compressive strength (2-6 MPa) similar to cancellous bone made them suitable for low-load bearing applications. Despite the fact that final setting times of biomicroconcretes were longer than recommended in the literature (i.e., exceeded 15 min), their short cohesion time allows for a successful implantation in a rabbit femoral defect model. Histological analysis and Raman studies revealed newly formed bone tissues around the sides of implanted materials. Furthermore, the process of neovascularization and reconstruction of the bone tissue, as well as a reverse scaffolding process, was visible. No signs of inflammation or adverse tissue reactions were observed during the experiment.

A Collagen Based Cryogel Bioscaffold that Generates Oxygen for Islet Transplantation.

The aim of this work was to develop, characterize and test a novel 3D bioscaffold matrix which can accommodate pancreatic islets and provide them with a continuous, controlled and steady source of oxygen to prevent hypoxia-induced damage following transplantation. Hence, we made a collagen based cryogel bioscaffold which incorporated calcium peroxide (CPO) into its matrix. The optimal concentration of CPO integrated into bioscaffolds was 0.25wt.% and this generated oxygen at 0.21±0.02mM/day (day 1), 0.19±0.01mM/day (day 6), 0.13±0.03mM/day (day 14), and 0.14±0.02mM/day (day 21). Accordingly, islets seeded into cryogel-CPO bioscaffolds had a significantly higher viability and function compared to islets seeded into cryogel alone bioscaffolds or islets cultured alone on traditional cell culture plates; these findings were supported by data from quantitative computational modelling. When syngeneic islets were transplanted into the epididymal fat pad (EFP) of diabetic mice, our cryogel-0.25wt.%CPO bioscaffold improved islet function with diabetic animals re-establishing glycemic control. Mice transplanted with cryogel-0.25wt.%CPO bioscaffolds showed faster responses to intraperitoneal glucose injections and had a higher level of insulin content in their EFP compared to those transplanted with islets alone (P<0.05). Biodegradability studies predicted that our cryogel-CPO bioscaffolds will have long-lasting biostability for approximately 5 years (biodegradation rate: 16.00±0.65%/year). Long term implantation studies (i.e. 6 months) showed that our cryogel-CPO bioscaffold is biocompatible and integrated into the surrounding fat tissue with minimal adverse tissue reaction; this was further supported by no change in blood parameters (i.e. electrolyte, metabolic, chemistry and liver panels). Our novel oxygen-generating bioscaffold (i.e. cryogel-0.25wt.%CPO) therefore provides a biostable and biocompatible 3D microenvironment for islets which can facilitate islet survival and function at extra-hepatic sites of transplantation.

Mitochondrial ROS Formation in the Pathogenesis of Diabetic Cardiomyopathy.

Diabetic cardiomyopathy is a result of diabetes-induced changes in the structure and function of the heart. Hyperglycemia affects multiple pathways in the diabetic heart, but excessive reactive oxygen species (ROS) generation and oxidative stress represent common denominators associated with adverse tissue remodeling. Indeed, key processes underlying cardiac remodeling in diabetes are redox sensitive, including inflammation, organelle dysfunction, alteration in ion homeostasis, cardiomyocyte hypertrophy, apoptosis, fibrosis, and contractile dysfunction. Extensive experimental evidence supports the involvement of mitochondrial ROS formation in the alterations characterizing the diabetic heart. In this review we will outline the central role of mitochondrial ROS and alterations in the redox status contributing to the development of diabetic cardiomyopathy. We will discuss the role of different sources of ROS involved in this process, with a specific emphasis on mitochondrial ROS producing enzymes within cardiomyocytes. Finally, the therapeutic potential of pharmacological inhibitors of ROS sources within the mitochondria will be discussed.

Outcome of Re-Revision Surgery for Adverse Local Tissue Reaction in Metal-on-Polyethylene and Metal-on-Metal Total Hip Arthroplasty

BackgroundAdverse local tissue reactions (ALTRs), initially described as a complication of metal-on-metal (MoM) total hip arthroplasty (THA), have also become an important risk factor for implant failure requiring revision surgery in metal-on-polyethylene (MoP) THA due to modular taper corrosion. This study aims to report early complication rates and outcomes as well as potential risk factors for a re-revision. MethodsA total of 252 consecutive THA patients who underwent revision for ALTR were reviewed. There were 40 patients (16%) who underwent a second revision: (1) 26 MoP patients with modular taper corrosion and (2) 14 MoM patients. Patient demographics as well as clinical information were analyzed. Binary logistic regression was used to test for associations between re-revision surgery and clinical parameters. ResultsThe overall complication rate following initial revision for ALTR was 21%. Sixteen percent of these revision patients required a re-revision. The most common indication for re-revision was dislocation (45%). The complication rate was 35% following a re-revision which included dislocation (36%), infection (36%), fracture (14%), and implant loosening (14%). The rate of patients requiring a third revision was 23% with the most common indications being dislocation (33%) and infection (33%) (P = .032). ConclusionHigh rate of early complications (35%) and third revisions (23%) were observed following re-revision of symptomatic ALTR patients with those requiring re-revision associated with extensive intraoperative tissue necrosis. These findings provide clinically useful information that may assist surgeons in clinical decision making and preoperative counseling of both MoM and MoP patients undergoing re-revision surgery for ALTR.

Cranial flap fixation in sheep using a resorbable bone adhesive.

The authors' goal in this study was to investigate the use of a novel, bioresorbable, osteoconductive, wet-field mineral-organic bone adhesive composed of tetracalcium phosphate and phosphoserine (TTCP-PS) for cranial bone flap fixation and compare it with conventional low-profile titanium plates and self-drilling screws. An ovine craniotomy surgical model was used to evaluate the safety and efficacy of TTCP-PS over 2 years. Bilateral cranial defects were created in 41 sheep and were replaced in their original position. The gaps (kerfs) were completely filled with TTCP-PS (T1 group), half-filled with TTCP-PS (T2 group), or left empty and the flaps fixated by plates and screws as a control (C group). At 12 weeks, 1 year, and 2 years following surgery, the extent of bone healing, local tissue effects, and remodeling of the TTCP-PS were analyzed using macroscopic observations and histopathological and histomorphometric analyses. Flap fixation strength was evaluated by biomechanical testing at 12 weeks and 1 year postoperatively. No adverse local tissue effects were observed in any group. At 12 weeks, the bone flap fixation strengths in test group 1 (1689 ± 574 N) and test group 2 (1611 ± 501 N) were both statistically greater (p = 0.01) than that in the control group (663 ± 385 N). From 12 weeks to 1 year, the bone flap fixation strengths increased significantly (p < 0.05) for all groups. At 1 year, the flap fixation strength in test group 1 (3240 ± 423 N) and test group 2 (3212 ± 662 N) were both statistically greater (p = 0.04 and p = 0.02, respectively) than that in the control group (2418 ± 1463 N); however, there was no statistically significant difference in the strengths when comparing the test groups at both timepoints. Test group 1 had the best overall performance based on histomorphometric evaluation and biomechanical testing. At 2 years postoperatively, the kerfs filled with TTCP-PS had histological evidence of osteoconduction and replacement of TTCP-PS by bone with nearly complete osteointegration. TTCP-PS was demonstrated to be safe and effective for cranial flap fixation in an ovine model. In this study, the bioresorbable, osteoconductive bone adhesive appeared to have multiple advantages over standard plate-and-screw bone flap fixation, including biomechanical superiority, more complete and faster bony healing across the flap kerfs without fibrosis, and the minimization of bone flap and/or hardware migration and loosening. These properties of TTCP-PS may improve human cranial bone flap fixation and cranioplasty.

Protective effect of N-acetyl cysteine against radiotherapy-induced cardiac damage

Purpose: Although radiotherapy (RT) is an important component of cancer treatment, it induces adverse tissue reactions in the around of cancer tissue. Therefore, radioprotectives are needed to protect normal tissues. The aim of this study was to investigate the radioprotective effect of N-acetylcysteine (NAC) on RT-induced cardiac damage in rats for the acute term.Materials and methods: The animals were divided into four groups. The rats in control group were injected with saline for 7 d; the rats in NAC group were injected NAC at dose of 240 mg/kg d for 7 d; the rats in RT group were injected with saline for 7 d plus was irradiated 1 h after the last injection and the rats in NAC + RT group were injected with NAC for 7 d and irradiated 1 h after the last NAC dose. The electrocardiogram was recorded and evaluated PR interval, QRS duration, QT interval, T wave alterations and heart rate. Serum interleukin-4, interleukin-6, tumor necrosis factor-alpha, interleukin 1 beta, galectin-3 levels and creatine kinase and creatine kinase isoenzyme-MB activities were determined in all groups. Also, tissue malondialdehyde (MDA) and nitric oxide levels, superoxide dismutase, catalase and glutathione peroxidase activities were determined. In addition, histological changes of heart were evaluated. All measurements were performed 24 h after RT.Results: In the RT group, findings supporting cardiac injury were observed in the electrocardiogram. Also, cytokine levels and oxidative stress were significantly increased. Pretreatment of rats with NAC ameliorated cardiac injury induced by RT.Conclusions: Our findings suggested that NAC may be a potential radioprotector which is capable of preventing cardiac damage.

Fast dissolving glucose porogens for early calcium phosphate cement degradation and bone regeneration

Here, we demonstrate the in vivo efficacy of glucose microparticles (GMPs) to serve as porogens within calcium phosphate cements (CPCs) to obtain a fast-degrading bone substitute material. Composites were fabricated incorporating 20 wt% GMPs at two different GMP size ranges (100–150 μm (GMP-S) and 150–300 μm (GMP-L)), while CPC containing 20 wt% poly(lactic-co-glycolic acid) microparticles (PLGA) and plain CPC served as controls. After 2 and 8 weeks implantation in a rat femoral condyle defect model, specimens were retrieved and analyzed for material degradation and bone formation. Histologically, no adverse tissue response to any of the CPC-formulations was observed. All CPC-porogen formulations showed faster degradation compared to plain CPC control, but only GMP-containing formulations showed higher amounts of new bone formation compared to plain CPC controls. After 8 weeks, only CPC-porogen formulations with GMP-S or PLGA porogens showed higher degradation compared to plain CPC controls. Overall, the inclusion of GMPs into CPCs resulted in a macroporous structure that initially accelerated the generation of new bone. These findings highlight the efficacy of a novel approach that leverages simple porogen properties to generate porous CPCs with distinct degradation and bone regeneration profiles.

How to Interpret Metal Ions in THA

BackgroundModern total hip arthroplasty has seen an unfortunate increase in proportional implant failures secondary to adverse local tissue reactions (ALTRs) secondary to wear of metal-on-metal (MoM) bearings and mechanically assisted crevice corrosion (MACC) related to corrosion at implant junctions and tapers. The purpose of this study is to describe the appropriate choice of metal ion testing and evaluation of those levels to identify failed total hip arthroplasty implants containing cobalt and chromium. MethodsWhen presented with an arthroplasty of concern, the surgeon must determine what metal ion levels to obtain and then incorporate those levels into a treatment algorithm. Patients with painful hip arthroplasties are evaluated for chromium and cobalt by obtaining whole blood and synovial metal levels. ResultsSynovial fluid cobalt had the highest correlation with ALTR compared with the other tests, with a threshold of 19.75 ng/ml, with a specificity of 89%, if the cobalt-to-chromium ratio is greater than 1.4 ng/ml in a metal on polyethylene hip, with a sensitivity of 95%. ConclusionThe interpretation of whole blood metal ions is a key component of the algorithm in treating the symptomatic hip arthroplasty but is not to be used in a vacuum.

How Useful Is Magnetic Resonance Imaging in Evaluating Adverse Local Tissue Reaction?

Biologic failures of hip arthroplasty have emerged as an increasing threat to the longevity of the prosthesis. While wear of modern-day bearings has been greatly reduced with the advent of cross-linked polyethylene, local reaction to metal particles either from the bearing itself or to any of the modular tapers appears to be on the rise. Monitoring of these reactions by the use of plain radiographs or serum markers appears to be insufficient to gauge the gravity of the response.Over the past decade, the use of magnetic resonance imaging (MRI) techniques has emerged as the superior noninvasive instrument to assess the extent of soft tissue reaction around hip implants. The use of MRI around implants was initially challenging due to the presence of relatively high ferrous metals especially cobalt which causes local distortion of the magnetic fields. Novel changes in pulse sequencing have greatly improved the sensitivity and specificity of MRI so that at this time, MR is the most predictive diagnostic tool in evaluating the extent of tissue destruction. We feel strongly that modern MRI techniques are the most important tool in the workup of the patient suspected of having an adverse tissue reaction after hip arthroplasty.

What Surgeons Need to Know About Adverse Local Tissue Reaction in Total Hip Arthroplasty

Adverse local tissue reactions (ALTRs) were first associated with patients with failed metal-on-metal surface replacements and total hip arthroplasty (THA). However, an increasing number of cases of ALTR in metal-on-polyethylene (MOP) THA patients is being reported. Clinically, ALTR appears as benign, aseptic masses or bursae in the periprosthetic tissues. Histopathologically, ALTRs are distinguished by an intense lymphocyte infiltrate, destruction of the synovial surfaces, widespread necrosis, and fibrin exudate. Tribocorrosion of modular junctions appears to be the cause of ALTR in MOP patients. The various tribocorrosion damage modes occurring at modular junctions produce metal ions and a diversity of particulates in relation to size, chemical composition, and structure. The mechanisms by which these various products of tribocorrosion lead to ALTR are still a matter of considerable research. This review clarifies what constitutes ALTR, its relationship to implant factors, and highlights current methods for diagnosis and management of patients with ALTR in the setting of MOP THA.

Long-term study on the osteogenetic capability and mechanical behavior of a new resorbable biocomposite anchor in a canine model

BackgroundBiodegradable suture anchors are commonly used for repairing torn rotator cuffs, but these biodegradable materials still suffer from low mechanical strength, poor osteointegration, and the generation of acidic degradation byproducts. MethodThe purpose of this study was to evaluate the long-term mechanical behavior and osteogenetic capabilities of a biocomposite anchor injection molded with 30% β-tricalcium phosphate microparticles blended with 70% poly (L-lactide-co-glycolide) (85/15). This study investigated in vitro degradation and in vivo bone formation in a canine model. The initial mechanical behavior, mechanical strength retention with degradation time, and degradation features were investigated. ResultsThe results showed that the biocomposite anchor had sufficient initial mechanical stability confirmed by comparing the initial shear load on the anchor with the minimum shear load borne by an ankle fracture fixation screw, which is considered a worst-case implantation site for mechanical loading. The maximum shear load retention of the biocomposite anchor was 83% at 12 weeks, which is desirable, as it aligns with the rate of bone healing. The β-tricalcium phosphate fillers were evenly dispersed in the polymeric matrix and acted to slow the degradation rate and improve the mechanical strength of the anchor. The interface characteristics between the β-tricalcium phosphate particles and the polymeric matrix changed the degradation behavior of the biocomposite. Phosphate buffer saline was shown to diffuse through the interface into the biocomposite to inhibit the core accelerated degradation rate. In vivo, the addition of β-tricalcium phosphate induced new bone formation. The biocomposite material developed in this study demonstrated improved osteogenesis in comparison to a plain poly (L-lactide-co-glycolide) material. Neither anchor produced adverse tissue reactions, indicating that the biocomposite had favorable biocompatibility following long-term implantation. ConclusionIn summary, the new biocomposite anchor presented in this study had favorable osteogenetic capability, mechanical property, and controlled degradation rate for bone fixation. Translational potential of this articleThe new biocomposite anchor had sufficient initial and long-term fixation stability and bone formation capability in the canine model. It is indicated that the new biocomposite anchor has a ​potential for orthopedic application.

Adverse Local Tissue Reactions in Total Hip Arthroplasty: Who, When, and How to Revise

Adverse local tissue reaction (ALTR) has initially been described as a complication in metal-on-metal total hip arthroplasty (THA) [ 1 Kwon Y.-M. Glyn-Jones S. Simpson D.J. Kamali A. McLardy-Smith P. Gill H.S. et al. Analysis of wear of retrieved metal-on-metal hip resurfacing implants revised due to pseudotumours. J Bone Joint Surg Br. 2010; 92: 356-361https://doi.org/10.1302/0301-620X.92B3.23281 Crossref PubMed Scopus (185) Google Scholar , 2 Kwon Y.-M. Fehring T.K. Lombardi A.V. Barnes C.L. Cabanela M.E. Jacobs J.J. Risk stratification algorithm for management of patients with dual modular taper total hip arthroplasty: consensus statement of the American Association of Hip and Knee Surgeons, the American Academy of Orthopaedic Surgeons and the Hip Society. J Arthroplasty. 2014; 29: 2060-2064https://doi.org/10.1016/j.arth.2014.07.029 Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar , 3 Liow M.H.L. Kwon Y.-M. Metal-on-metal total hip arthroplasty: risk factors for pseudotumours and clinical systematic evaluation. Int Orthop. 2017; 41: 885-892https://doi.org/10.1007/s00264-016-3305-1 Crossref PubMed Scopus (37) Google Scholar , 4 Kwon Y.-M. Cross-sectional imaging in evaluation of soft tissue reactions secondary to metal debris. J Arthroplasty. 2014; 29: 653-656https://doi.org/10.1016/j.arth.2014.02.007 Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar , 5 MacDonald S.J. Brodner W. Jacobs J.J. A consensus paper on metal ions in metal-on-metal hip arthroplasties. J Arthroplasty. 2004; 19: 12-16https://doi.org/10.1016/j.arth.2004.09.009 Abstract Full Text Full Text PDF PubMed Scopus (131) Google Scholar ]. However, there have recently been increasing concerns regarding the occurrence of ALTR in metal-on-polyethylene THA due to corrosion at the head-neck taper junction in a process described as mechanically assisted crevice corrosion [ [6] Jacobs J.J. Gilbert J.L. Urban R.M. Corrosion of metal orthopaedic implants. J Bone Joint Surg Am. 1998; 80: 268-282https://doi.org/10.2106/00004623-199802000-00015 Crossref PubMed Scopus (743) Google Scholar ]. The generation of biologically active, nanometer-sized metal particles and metal ions from the arthroplasty bearing surfaces and taper junctions has been associated with the occurrence of localized, adverse periprosthetic soft tissue response, which has been recently recognized as an important emerging mode of failure in THA patients [ 7 Liow M.H.L. Urish K.L. Preffer F.I. Nielson G.P. Kwon Y.-M. Metal ion levels are not correlated with histopathology of adverse local tissue reactions in taper corrosion of total hip arthroplasty. J Arthroplasty. 2016; 31: 1797-1802https://doi.org/10.1016/j.arth.2016.01.041 Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar , 8 Kwon Y.-M. MacAuliffe J. Arauz P.G. Peng Y. Sensitivity and specificity of metal ion level in predicting adverse local tissue reactions due to head-neck taper corrosion in primary metal-on-polyethylene total hip arthroplasty. J Arthroplasty. 2018; 33: 3025-3029https://doi.org/10.1016/j.arth.2018.04.007 Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar , 9 Cooper H.J. Urban R.M. Wixson R.L. Meneghini R.M. Jacobs J.J. Adverse local tissue reaction arising from corrosion at the femoral neck-body junction in a dual-taper stem with a cobalt-chromium modular neck. J Bone Joint Surg Am. 2013; 95: 865-872https://doi.org/10.2106/JBJS.L.01042 Crossref PubMed Scopus (296) Google Scholar , 10 Vendittoli P.-A. Roy A. Mottard S. Girard J. Lusignan D. Lavigne M. Metal ion release from bearing wear and corrosion with 28 mm and large-diameter metal-on-metal bearing articulations: a follow-up study. J Bone Joint Surg Br. 2010; 92: 12-19https://doi.org/10.1302/0301-620X.92B1.22226 Crossref PubMed Scopus (100) Google Scholar , 11 Seon J.-K. Park J.-K. Shin Y.-J. Seo H.-Y. Lee K.-B. Song E.-K. Comparisons of kinematics and range of motion in high-flexion total knee arthroplasty: cruciate retaining vs. substituting designs. Knee Surg Sports Traumatol Arthrosc. 2011; 19: 2016-2022https://doi.org/10.1007/s00167-011-1434-z Crossref PubMed Scopus (51) Google Scholar ]. At the 2019 Annual Meeting of American Association of Hip and Knee Surgeons, the symposium on ALTRs with particular focus on “who, when, and how to revise” patients with ALTR was presented. The objectives of this symposium were to summarize clinical challenges in optimizing patient evaluation and revision surgery outcome. Specifically, the symposium presentations highlighted that there is a spectrum of clinical presentations of ALTRs due to taper corrosion and metal bearing surface wear, reflecting a complex interplay of implant, surgical, and patient factors. The current state of knowledge on the importance of various taper material combinations and taper design geometry on taper corrosion is evolving. A systematic risk stratification approach based on currently available data is critical in optimizing evaluation and revision surgery indications. The utility and limitations of specialized diagnostic tests including metal ion levels and cross-sectional imaging studies such as metal artifact reduction sequence magnetic resonance imaging in the clinical decision-making process is important in evaluation of these patients. Furthermore, optimizing revision surgery outcome for ALTRs involves careful preoperative planning, implant selection, and surgical techniques to overcome challenges associated with soft tissue necrosis.

In vitro evaluation of human myoblast function after exposure to cobalt and chromium ions.

The replacement of a native hip joint by a metal-on-metal prosthesis may induce deleterious inflammatory side effects that are associated with the release of wear particles and metal ions. These events are referred to the adverse reaction to metal debris (ARMD) and the adverse local tissue reaction (ALTR). While wear particles seem involved in ARMD, the role of metal ions in ALTR and their impact on myoblasts, located in the prosthesis vicinity, has not been fully identified. To clarify this issue we investigated, using an in vitro culture system, the effect of cobalt and/or chromium ions (Co2+ and/or Cr3+ ) on human myoblast proliferation, cellular differentiation, and inflammatory marker expression. Freshly isolated human myoblasts were cultured in media supplemented with graded concentrations of Co2+ and/or Cr3+ . Co2+ induced a concentration-dependent decrease of both myoblast viability and myogenic differentiation while Cr3+ did not. Co2+ or Co2+ /Cr3+ also induced the upregulation of ICAM-1, whereas HLA-DR expression was unaffected. Moreover, allogenic monocytes induced the synergistic increase of Co2+ -induced ICAM-1 expression. We also found that Co2+ stabilized HIF-1α and increased TLR4, tumor necrosis factor-alpha (TNF-α), and interleukin 1β (IL-1β) expression in a dose and time-dependent manner in human myoblasts. This study showed that Co2+ , but not Cr3+ , was toxic toward myoblasts and induced, in the surviving cells, expression of inflammatory markers such as ICAM-1, TLR4, TNF-α, and IL-1β. This suggests that Co2+ , most efficiently in the presence of monocytes, may be a key inducer of ALTR, which may, if severe and long-lasting, eventually result in prosthesis loosening.

Accolade TMZF trunnion corrosion and mechanical failure 9 yr after primary surgery: A case report and treatment options

Accolade TMZF trunnion corrosion and mechanical failure 9 yr after primary surgery: A case report and treatment options

Progression of adverse local tissue reaction in ASR metal-on-metal hip arthroplasty: a longitudinal MARS-MRI study at mid- to long-term.

Despite the large number of studies assessing adverse local tissue reaction (ALTR) in metal-on-metal (MoM) hip implants, there is still a lack of knowledge about the natural progression of ALTR. The aims of this study were to describe the natural course of changes in ALTR at mid- to long-term follow-up for patients treated with metal-on-metal hip arthroplasty and to determine possible risk factors associated with change in ALTR. A total of 158 patients (158 hips), 109 MoM hip resurfacing arthroplasties (HRAs) and 49 MoM total hip arthroplasties (THAs), with 2 clinical follow-ups including MARS-MRIs were included. The mean time from index operation to the first visit was 7.6 years (range 3.4-11.4 years), and the mean time between the 2 visits was 1.0 year (range 0.7-1.6 years). The proportion of patients with moderate or severe ALTR did not increase significantly between the first and second visit for the MoM HRA group (14.7-15.6%; p = 0.850) or the MoM THA group (32.7-36.7%; p = 0.671). 8 (7.3%) HRA patients and 9 (18.4%) THA patients progressed in ALTR grade. None of the collected clinical variables was sensitive or specific in identifying patients with ALTR progression. Although ALTR prevalence was high in our cohort, clinically significant ALTR progression was rare. We were unable to find any predictors associated with ALTR change. This indicates that MARS-MRI remains a valuable tool in the follow-up of patients treated with MoM hip devices in identifying patients who may need revision surgery.

Use of Silk Proteins to Form Organic, Flexible, Degradable Biosensors for Metabolite Monitoring

The development of sustainable and degradable biosensors and bioelectronics has implications for implantable systems, as well in addressing issues of electronic waste. Mechanically flexible and bioresorbable sensors can find applications at soft biological interfaces. While devices typically use metallic and synthetic components and interconnects that are non-degradable, or have the potential to cause adverse tissue reactions, the use of nature-derived materials and conducting polymers can provide distinct advantages. In particular, silk fibroin and sericin can provide a unique complement of properties, providing both structural and functional elements. Here, a fully organic, mechanically flexible biosensor in an integrated 3-electrode configuration is demonstrated. Silk sericin conducting ink is micropatterned on a silk fibroin substrate using a facile photolithographic process. Next, using a conducting polymer wire sheathed in silk fibroin, organic interconnects are used to form the electrical connections. This fully organic electrochemical system has competitive performance metrics for sensing in comparison to conventional systems, as verified by detection of a model analyte – ascorbic acid. The stability of the silk biosensor through biodegradation was observed, showing that the sensors can function for several days prior to failure. Such protein-based systems can provide a useful tool for biomonitoring of analytes in the body or environment for controlled periods of time, followed by complete degradation, as transient systems for various applications.

What Are the Contemporary Etiologies for Revision Surgery and Revision After Primary, Noncemented Total Hip Arthroplasty?

Contemporary failure etiologies of primary total hip arthroplasties (THAs) have not been precisely defined because of heterogeneity of referral practices. A single-institution registry of 4,555 primary, noncemented THAs performed by subspecialty trained arthroplasty surgeons between 2000 and 2012 was analyzed. Only revision surgeries and revisions that occurred after THAs initially performed at the institution were included. The estimated 10-year survivorships free from THA revision surgery, modular implant revision, and nonmodular implant revision were 98.2%, 98.1%, and 96.3%, respectively. The most common reasons for revision surgeries were wound-related complications (49%), periprosthetic fracture (25%), and pain (18%). Hip instability (53%) and acute periprosthetic joint infection (26%) were the most common etiologies of revision procedures with isolated exchange of at least one modular implant. The most common reasons for replacement or removal of nonmodular implant were periprosthetic fracture (32%), aseptic loosening (22%), and adverse tissue reaction (17%). Focusing on primary THAs initially performed by a contemporary, subspecialty practice allowed an accurate determination of etiologies and rates of failure (defined by revision surgery or revision) after THA. Level IV.

Strategy to improve the mechanical properties of bioabsorbable materials based on chitosan for orthopedic fixation applications

Bioabsorbable polymeric fixation devices have been used as an alternative to metallic implants in orthopedics, preventing the stress shielding effect and avoiding a second surgery for implant removal. However, several problems are still associated with current bioabsorbable implants, including the limited mechanical stiffness and strength, and the adverse tissue reactions generated. To minimize or even eliminate the problems associated with these implants, strategies have been developed to synthesize new implant materials based on chitosan. To overcome the brittle behavior of most 3D chitosan-based structures, glycerol and sorbitol were blended to chitosan and the effect of these plasticizers in the produced specimens was analyzed by flexural tests, Berkovich tests, scanning electron microscopy (SEM) and micro-CT analyzes. The improvement of the mechanical properties was also tested by adding ceramics, namely hydroxyapatite powder and biphasic mixtures of hydroxyapatite (HA) and beta-tricalcium phosphate (β-TCP). In the plasticizers group, the best combination of the measured properties was obtained for chitosan with 10% glycerol (flexural strength of 53.8 MPa and indentation hardness of 19.4 kgf/mm2), while in the ceramics group the best mechanical behavior was obtained for chitosan with 10% HA+β-TCP powder (flexural strength of 67.5 MPa and indentation hardness 28.2 kgf/mm2). All the tested material compositions were dense and homogeneous, fundamental condition for a good implant performance. These are encouraging results, which support the continued development of chitosan-based materials for orthopedic fixation applications.

Cobalt and Chromium Ion Release in Metal-on-Polyethylene and Ceramic-on-Polyethylene THA: A Simulator Study With Cellular and Microbiological Correlations

BackgroundThe aims of this study were to determine the levels of cobalt (Co) and chromium (Cr) ions generated in simulators from metal-on-polyethylene (MoP) and ceramic-on-polyethylene (CoP) constructs. Furthermore, we aimed to investigate the cytotoxic effect of these ion levels on native tissues and their potential to modify periprosthetic joint infection risk. MethodsWe used in vitro culture of human adipose-derived mesenchymal stem cells (AMSCs) and Staphylococcus epidermidis cultures, respectively. Ten hip simulator constructs (5 MoP and 5 CoP) were assembled and run for 1,000,000 cycles in bovine serum and evaluated for CoCr concentration. Cytotoxicity and growth impact on AMSCs and S. epidermidis was compared between CoCr and inert silicon dioxide. ResultsAfter 1,000,000 cycles, mean MoP and CoP Co concentration was 2264 and 0.6 ng/mL, respectively (P < .001). Mean MoP and CoP Cr concentration was 217 and 4.3 ng/mL, respectively (P < .001). Mean MoP Co:Cr ratio was 10:1. Co ions were significantly more toxic to human AMSCs than control silicon dioxide in a dose-response manner (P < .001). S. epidermidis growth was not significantly impacted by Co concentrations observed in the simulators. ConclusionMoP constructs built in ideal conditions generated substantial CoCr debris, highlighting a baseline risk with these implants that may be exacerbated by host factors or imperfect surgical technique. Evaluation of impact on AMSCs suggests that debris levels produced under simulator conditions can be cytotoxic. In addition, these concentrations did not potentiate or inhibit S. epidermidis growth, suggesting that elevated periprosthetic joint infection rates with adverse local tissue reaction are related to other factors potentially associated with tissue necrosis.

Universal surface modification using dopamine-hyaluronic acid conjugates for anti-biofouling

Various materials are used to make implantable devices such as pumps, catheters, and stimulators. However, such implants inevitably undergo biofouling, which is associated with non-specific proteins and cell adhesion on the material surfaces. Severe biofouling often leads to adverse tissue reactions, such as foreign body responses, and thick scar tissue formation around the implantation, which in turn hampers the function and performance of the implants. Herein, a simple and effective surface modification method using dopamine-hyaluronic acid conjugate (DA-HA) is demonstrated to implement anti-biofouling in various biomaterials. DA-HA was synthesized and utilized as a coating material and five commonly used implantable substrates (i.e., polyimide (PI), gold (Au), poly(methyl methacrylate) (PMMA), polytetrafluoroethylene (PTFE), and polyurethane (PU)) were tested for modification with DA-HA. Highly hydrophilic HA chains were immobilized on the substrate surfaces through self-polymerization of DA-HA at an alkaline pH. The DA-HA-modified substrates displayed significant resistance to both non-specific protein adsorption and cell adhesion on the surfaces. In addition, a reduction in scar tissue formation was observed in the DA-HA-coated substrates compared to the unmodified bare substrates after a 4-week subcutaneous implantation. This universal surface coating can be further implemented in various biomedical applications in which severe biofouling is highly undesirable.