Fixation of the glenoid component is critical to the outcome of total shoulder arthroplasty. In an in vitro study, we analysed the effect of surface design and thickness of the cement mantle on the pull-out strength of the polyethylene pegs which are considered essential for fixation of cemented glenoid components. The macrostructure and surface of the pegs and the thickness of the cement mantle were studied in human glenoid bone. The lowest pull-out forces, 20 ± 5 N, were for cylindrical pegs with a smooth surface fixed in the glenoid with a thin cement mantle. The highest values, 425 ± 7 N, were for threaded pegs fixed with a thicker cement mantle. Increasing the diameter of the hole into which the peg is inserted from 5.2 to 6.2 mm thereby increasing the thickness of the cement mantle, improved the mean pull-out force for the pegs tested

Intraneural electrodes can be harnessed to control neural prosthetic devices in human amputees. However, in chronic implants we witness a gradual loss of device functionality and electrode isolation due to a nonspecific inflammatory response to the implanted material, called foreign body reaction (FBR). FBR may eventually lead to a fibrous encapsulation of the electrode surface. Poly(ethylene glycol) (PEG) is one of the most common low-fouling materials used to coat and protect electrode surfaces. Yet, PEG can easily undergo encapsulation and oxidative damage in long-term in vivo applications. Poly(sulfobetaine methacrylate) - poly(SBMA) - zwitterionic hydrogels may represent more promising alternatives to minimize the FBR due to their ultra-low fouling features. Here, we tested and compared the poly(SBMA) zwitterionic hydrogel coating with the PEG coating in reducing adhesion and activation of pro-inflammatory and pro-fibrotic cells to polyimide surfaces, which are early hallmarks of FBR. We aimed to coat polyimide surfaces with a hydrogel thin film and analysed the release of a model drug from the hydrogel. We performed hydrogel synthesis, mechanical characterization and biocompatibility analysis. Cell adhesion, viability and morphology of human myofibroblasts cultured on PEG- and hydrogel-coated surfaces were evaluated through confocal microscopy-based high-content analysis (HCA). Reduced activation of pro-inflammatory human macrophages cultured on hydrogels was assessed as well as the hydrogel drug release profile. Because of its high hydration, biocompatibility, low stiffness and ultra-low fouling characteristics the hydrogel enabled lower adhesion and activation of pro-inflammatory and pro-fibrotic cells vs. polystyrene controls, and showed a long-term release of the anti-fibrotic drug Everolimus. Furthermore, a polyimide surface was successfully coated with a hydrogel thin film. Our soft zwitterionic hydrogel could outperform PEG as more suitable coating material of neural electrodes for mitigating the FBR. Such poly(SBMA)-based biomaterial could also be envisioned as long-term delivery system for a sustained release of anti-inflammatory and anti-fibrotic drugs in vivo

The degeneration of the intervertebral disc (IVD) is the primary cause for low back pain, which is treated with surgical interventions such as spinal fusion. A strategy to develop a regenerative and non-invasive treatment requires an injectable cell carrier system. Our efforts have focussed on developing a hyaluronan (HA)-based hydrogel system that can be used as a carrier for therapeutic agents in annulus fibrosus (AF) repair. High molecular weight HA at 20mM is chemically crosslinked with varying concentrations of 4-arm PEG. Hydrogels were optimised for degree of crosslinking, stability and rheological properties. Subsequently, the morphology and viability of the human AF cells encapsulated in the hydrogels were studied. The highest crosslinking was seen with 4-arm PEG at 1:1 HA:PEG molar ratio. This was the most stable against enzymatic and hydrolytic degradation, and had greater swelling property, which is desired as the degeneration decreases the water retention capability of the IVD. The gelation time, important for in situ injectability, was under five minutes for all formulations. Storage modulus was between 0.4–1.1 kPa. Compared to 2D cultures, cells were rounder after encapsulation, mimicking the native microenvironment, and had the similar metabolic activity for seven days. AF cells encapsulated in HA/4-arm PEG hydrogel were stiffer compared to the nucleus pulposus (NP) cells encapsulated similarly as measured with Brillouin microscopy. The 4-arm PEG crosslinked HA-based hydrogel system promises to be a candidate for an injectable carrier for cells for AF repair and regeneration

Invasive intraneural electrodes implanted in peripheral nerves are neural prosthetic devices that are exploied to control advanced neural-interfaced prostheses in human amputees. One of the main issues to be faced in chronic implants is represented by the gradual loss of functionality of such intraneural interfaces due to an electrical impedance increase caused by the progressive formation of a fibrotic capsule around the electrodes, which is originally due to a nonspecific inflammatory response called foreign body reaction (FBR). In this in vitro work, we tested the biocompatibility and ultra-low fouling features of the synthetic coating - poly(ethylene glycol) (PEG) - compared to the organic polymer - zwitterionic sulfated poly(sulfobetaine methacrylate) (SBMA) hydrogel - to prevent or reduce the first steps of the FBR: plasma protein adsorption and cell adhesion to the interface. Synthesis and characterization of the SBMA hydrogel was done. Preliminary biocompatibility analysis of the zwitterionic hydrogel, using hydrogel-conditioned medium, showed no cytotoxicity at all vs. control. We seeded GFP-labelled human myofibroblasts on PEG- and SBMA hydrogel-coated polyimide surfaces and evaluated their adhesion and cell viability at different time-points. Because of the high hydration, low stiffness reflecting the one of neural tissue, and ultra-low fouling characteristics of the SBMA hydrogel, this polymer showed lower myofibroblast adhesion and different cell morphology compared to adhesion controls, thereby representing a better coating than PEG for potentially mitigating the FBR. We conclude that soft SBMA hydrogels could outperform PEG coatings in vitro as more suitable dressings of intraneural electrodes. Furthermore, such SBMA-based antifouling materials can be envisioned as long-term diffusion-based delivery systems for controlled release of anti-inflammatory and anti-fibrotic drugs in vivo

Prosthetic joint infections represent complications connected to the implantation of biomedical devices. Bacterial biofilm is one of the main issues causing infections from contaminated orthopaedic prostheses. Biofilm is a structured community of microbial cells that are firmly attached to a surface and have unique metabolic and physiological attributes that induce improved resistance to environmental stresses including toxic compounds like antimicrobial molecules (e.g. antibiotics). Therefore, there is increasing need to develop methods/treatments exerting antibacterial activities not only against planktonic (suspended) cells but also against adherent cells of pathogenic microorganisms forming biofilms. In this context, metal-based coatings with antibacterial activities have been widely investigated and used in the clinical practice. However, traditional coatings exhibit some drawbacks related to the insufficient adhesion to the substrate, scarce uniformity and scarce control over the toxic metal release reducing the biofilm formation prevention efficacy. Additionally, standardized and systematic approaches to test antibacterial activity of newly developed coatings are still missing, while standard microbiological tests (e.g. soft-agar assays) are typically used that are limited in terms of simultaneous conditions that can be tested, potentially leading to scarce reproducibility and reliability of the results. In this work, we combined the Calgary Biofilm Device (CBD) as a device for high-throughput screening, together with a novel plasma-assisted technique named Ionized Jet Deposition (IJD), to generate and test new generation of nanostructured silver- and zinc-based films as coatings for biomedical devices with antibacterial and antibiofilm properties. During the experiments we tested both planktonic and biofilm growth of four bacterial strains, two gram-positive and two gram-negative bacterial strains, i.e. Staphylococcus aureus ATCC 6538P, Enterococcus faecalis DP1122 and Escherichia coli ATCC 8739 and Pseudomonas aeruginosa PAO1, respectively. The use of CBD that had the only wells covered with the metal coatings while the biofilm supports (pegs) were not sheltered allowed to selectively define the toxic effect of the metal release (from the coating) against biofilm development in addition to the toxic activity exerted by contact killing mechanism (on biofilms formed on the coating). The results indicated that the antibacterial and antibiofilm effects of the metal coatings was at least partly gram staining dependent. Indeed, Gram negative bacterial strains showed high sensitivity toward silver in both planktonic growth and biofilm formation, whereas zinc coatings provided a significant inhibitory activity against Gram positive bacterial strains. Furthermore, the coatings showed the maximal activity against biofilms directly forming on them, although, Zn coating showed a strong effect against biofilms of gram-positive bacteria also formed on uncoated pegs. We conclude that the metal-based coatings newly developed and screened in this work are efficient against bacterial growth and adherence opening possible future applications for orthopedic protheses manufacturing

Introduction. Glenoid loosening, still a main complication for shoulder arthroplasty, was suggested to be related implant design, surgical aspects, and also bone quality. However, typical studies of fixation do not account for heterogeneity in bone morphology and density which were suggested to affect fixation failure. In this study, a combination of cyclic rocking horse tests on cadaver specimens and microCT-based finite element (microFE) analysis of specimens of a wide range of bone density were used to evaluate the effects of periprosthetic bone quality on the risks of loosening of anatomical keeled or pegged glenoid implants. Methods. Six pairs of cadaveric scapulae, scanned with a quantitative computer tomography (QCT) scanner to calculate bone mineral density (BMD), were implanted with either cemented anatomical pegged or keeled glenoid components and tested under constant glenohumeral load while a humeral head component was moved cyclically in the inferior and superior directions. Edge displacements were measured after 1000, 4000 and 23000 test cycles, and tested for statistical differences with regards to changes or implant design. Relationships were established between edge displacements and QCT-based BMD below the implant. Four other specimens were scanned with high-resolution peripheral QCT (82µm) and implanted with the same 2 implants to generate virtual models. These were loaded with constant glenohumeral force, varying glenohumeral conformity and superior or inferior load shifts while internal stresses at the cement-bone and implant-cement interfaces were calculated and related to apparent bone density in the periprosthetic zone. Results. Mean displacements at the inferior and superior edges showed no statistical difference between keeled and pegged designs (p>0.05). Compression and distraction were however statistically different from the initial reference measurement at even 1000 and 4000 cycles for both implant designs (p<0.05). For both implant designs, superior and inferior distractions were generally highest at each measurement time in specimens where BMD below the lifting edge was lower, showing a trend of increased distraction with decreased BMD. Moreover, the microFE models predicted higher bone and cement stresses for specimens of lower apparent bone density. Finally, highest peak stresses were located at the cement-bone interface, which seemed the weaker part of the fixation. Discussion. With this combined experimental and numerical study, it was shown that implant distraction and stresses in the cement layer are greater in glenoids of lower bone density for both implant designs. This indicates that fixation failure will most likely occur in bone of lower density, and that fixation design itself may play a secondary role. These results have important impact for understanding the mechanisms of glenoid component failure, a common complication of total shoulder arthroplasty

Introduction and Objective. In recent years, along with the extending longevity of patients and the increase in their functional demands, the number of annually performed RSA and the incidence of complications are also increasing. When a complication occurs, the patient often needs multiple surgeries to restore the function of the upper limb. Revision implants are directly responsible for the critical reduction of the bone stock, especially in the shoulder. The purpose of this paper is to report the use of allograft bone to restore the bone stock of the glenoid in the treatment of an aseptic glenoid component loosening after a reverse shoulder arthroplasty (RSA). Materials and Methods. An 86-years-old man came to our attention for aseptic glenoid component loosening after RSA. Plain radiographs showed a complete dislocation of the glenoid component with 2 broken screws in the neck of glenoid. CT scans confirmed the severe reduction of the glenoid bone stock and critical bone resorption and were used for the preoperative planning. To our opinion, given the critical bone defect, the only viable option was revision surgery with restoration of bone stock. We planned to use a bone graft harvested from distal bone bank femur as component augmentation. During the revision procedure the baseplate with a long central peg was implanted “on table” on the allograft and an appropriate osteotomy was made to customize the allograft on the glenoid defect according to the CT-based preoperative planning. The Bio-component was implanted with stable screws fixation on residual scapula. We decided not to replace the humeral component since it was stable and showed no signs of mobilization. Results. The new bio-implant was stable, and the patient gained a complete functional recovery of the shoulder. The scheduled radiological assessments up to 12 months showed no signs of bone resorption or mobilization of the glenoid component. Conclusions. The use of bone allograft in revision surgery after a RSA is a versatile and effective technique to treat severe glenoid bone loss and to improve the global stability of the implant. Furthermore, it represents a viable alternative to autologous graft since it requires shorter operative times and reduces graft site complications. There are very few data available regarding the use of allografts and, although the first studies are encouraging, further investigation is needed to determine the biological capabilities of the transplant and its validity in complex revisions after RSA

Complex pathophysiologies involve different signalling mechanisms, with a multitude of often interconnected potential therapeutic targets. Therefore, there is a need for the development of multi-compartment delivery vehicles for combinatorial and synergistic therapeutic approaches. In this study it was hypothesized that multi-compartment crosslinked collagen type I systems can deliver multiple bioactive agents in a controlled manner in an in vitro model condition of skin fibrosis. Multi-compartment collagen-based systems were made using solutions of dialyzed type I collagen mixed with 10× PBS, after which they were neutralised and crosslinked with 1 and 2.0 mM 4 arm-succinimidyl glutarate ester PEG (4 arm-PEG-SG), respectively, followed by incubation at 37ºC. The systems were characterised through swelling assessment, collagenase degradation assay and compression tests. The release of encapsulated drugs from the hydrogels was studied by ELISA and the effect of the delivered bioactive agents was assessed through imaging and quantification for fibrotic markers in an in vitro model. A pilot study using FITC-dextran proved that the inner compartment was capable of promoting a sustained release over a long period of time (7 days), which was further confirmed with drug release assays using a TNF-α antagonist and recombinant decorin, fitting the intended therapeutic release profile. Protein expression studies showed a decrease of endogenous collagen type I and α-smooth muscle actin expression (p<0.05) indicating amelioration of fibrosis. In summary, this indicates that this system is suitable for dual delivery of multiple bioactive agents, resulting in a controlled release in vitro and illustrating its potential in therapy

Background/Study Aim. Injectable scaffolds which also deliver cells and bioactive molecules to augment bone healing overcome many of the limitations associated with current bone graft substitutes. The aim of this study was to develop and test a novel injectable scaffold that self-assembles isothermically in situ to form a biodegradable porous osteoconductive material, and to assess the viability of human mesenchymal stem cells (hMSC) seeded onto the scaffold. Methods. Rheological assessment was performed on three different molecular weights (Mw) of poly(lactic-co-glycolic acid) (PLGA) (26kDa, 53kDa and 92kDa) combined with differing ratios of polyethylene glycol (PEG) to control the temperature required for scaffold self-assembly. The strength (MPa) and stiffness (Young's Modulus) patterns of the scaffolds were assessed in compression. The cell viability, proliferation and distribution patterns of hMSCs seeded within the scaffold were assessed through various assays (Alamar Blue), confocal microscopy and micro-CT. The hMSC differentiation in osteogenic media was characterised by the identification of specific bone formation markers (e.g. alkaline phosphatase). Results. Rheological assessment identified a stepwise control of the trigger-temperature required for scaffold self-assembly (37°C) through adjustment of PLGA Mw and PLGA/PEG ratios. Mechanical analysis of the scaffolds revealed compressive (2-6MPa) and stiffness (Young's Modulus of 10MPa) strengths similar to that of cancellous bone. Confocal microscopy analysis demonstrated the scaffold's interconnecting pores and biocompatibility supporting proliferation of viable HMSCs, and complemented data from cell proliferation assays. Identification of bone formation markers reinforced the scaffolds potential to provide a supporting osteoconductive environment for bone formation and deposition. Conclusions. This study has generated injectable scaffold formulations that self-assemble at physiologically relevant temperatures and possess compressive and stiffness strengths in the range of cancellous bone. It is possible to tailor the architecture/mechanical/biodegradable properties of the scaffold through manipulation of PLGA Mw, and PEG ratios. This injectable scaffold system provides a means of delivery for hMSCs (and growth factors or antibiotics) and is an architecturally suitable 3D scaffold that has the potential to be not only osteoconductive, but also osteoinductive and osteogenic

Infection of orthopaedic implants is a significant problem, with increased antibiotic resistance of adherent ‘biofilm’ bacteria causing difficulties in treatment. We have investigated the in vitro effect of a pulsed electromagnetic field (PEMF) on the efficacy of antibiotics in the treatment of infection of implants. Five-day biofilms of Staphylococcus epidermidis were grown on the tips of stainless-steel pegs. They were exposed for 12 hours to varying concentrations of gentamicin or vancomycin in microtitre trays at 37°C and 5% CO. 2. The test group were exposed to a PEMF. The control tray was not exposed to a PEMF. After exposure to antibiotic the pegs were incubated overnight, before standard plating onto blood agar for colony counting. Exposure to a PEMF increased the effectiveness of gentamicin against the five-day biofilms of Staphylococcus epidermidis. In three of five experiments there was reduction of at least 50% in the minimum biofilm inhibitory concentration. In a fourth experiment there was a two-log difference in colony count at 160 mg/l of gentamicin. Analysis of variance (ANOVA) confirmed an effect by a PEMF on the efficacy of gentamicin which was significant at p < 0.05. There was no significant effect with vancomycin

The intervertebral disc faces high compressive forces during daily activities. Axial compression induces creeping fluid loss and reduction in disc height. With degeneration, disc fluids and height are progressively lost, altering biomechanics. It is assumed that this loss of fluids is caused by a drop in osmolality in the disc due to proteoglycan depletion. Here we investigate the isolated effect of a reduction in osmosis on the biomechanical properties of the intervertebral disc. Continuous diurnal loading was applied to healthy caprine intervertebral discs in a loaded disc culture system for a total of 6 days. We increased testing bath osmolality with two doses of polyethylene-glycol (PEG), thereby reducing the osmotic gradient between the disc and the surrounding fluid. This way we could study the isolated effect of reduced osmosis on axial creep, without damaging the disc. We evaluated: daily creep and recovery, recovery time-constants and compressive stiffness. Additionally, we investigated water content. There was a strong dose-dependent effect of PEG concentration on water content and axial creep behaviour: disc height, amplitude and rate of creep and recovery were all significantly reduced. Axial compressive stiffness of the disc was not affected. Reduction of water content and amplitude of creep and recovery showed similarity to degenerative disc biomechanics. However, the time-constants increased, indicating that the hydraulic permeability was reduced, in contrast to what happens with degeneration. This suggests that besides the osmotic gradient, the permeability of the tissues determines healthy intervertebral disc biomechanics

Study Aim. Femoral components used in total knee arthroplasty (TKA) are primarily designed on the basis of kinematics and ease of fixation. This study considers the stress-strain environment in the distal femur due to different implant internal geometry variations (based on current industry standards) using finite element (FE) analyses. Both two and three dimensional models are considered for a range of physiological loading scenarios – from full extension to deep flexion. Issues associated with micro-motion at the bone-implant interface are also considered. Materials and methods. Two (plane strain) and three dimensional finite element analyses were conducted to examine implant micro-motions and stability. The simple 2D models were used to examine the influence of anterior-posterior (AP) flange angle on implant stability. AP slopes of 3°, 7° and 11° were considered with contact between bone and implant interfaces being modeled using the standard coulomb friction model. The direction and region of loading was based on loading experienced at full extension, 90° flexion and 135° flexion. Three main model variations were created for the 3D analyses, the first model represented an intact distal femur, the second a primary implanted distal femur and the third a distal femur implanted with a posterior stabilising implant. Further each of the above 3D model sets were divided into two group, the first used a frictional interface between the bone and implant to characterise the behavior of uncemented implants post TKA and the second group assumed 100% osseointegration had already taken place and focused on examining the subsequent stress/strain environment in the femur with respect to different femoral component geometries relative the intact distal femur model. Results and Discussion. Analyses indicate a trend relating the slope of the anterior-posterior (AP) flange to implant loosening at high flexion angles for uncemented components. Once cemented, this becomes less important. Results from the 3D analyses show that the posterior stabilising implant causes stress concentrations which can lead to bicondylar fatigue fracture. All femoral components cause stress shielding in cancellous bone particularly when they are fully bonded. Investigations into implant micromotion show that revision implants with box sections provided more resistance to micromotion than the pegged primary implants. However for the gait cycle tested the maximum recorded micromotion of both implants was well within acceptable levels for osseointegration to occur

Objectives

This systematic review aimed to assess the in vivo and clinical effect of strontium (Sr)-enriched biomaterials in bone formation and/or remodelling.

Although much has been published on the causes of slipped upper femoral epiphysis and the results of treatment, little attention has been given to the mechanism of the slip. This study presents the results of the analysis of 13 adolescent femora, and the attempts to reproduce the radiological appearances of a typical slip. The mean age of the skeletons was 13 years (11 to 15). It was found that the internal bony architecture in the zone of the growth plate was such that a slip of the epiphysis on the metaphysis (in the normal meaning of the word slip) could not take place, largely relating to the presence of a tubercle of bone projecting down from the epiphysis. The only way that the appearance of a typical slipped upper femoral epiphysis could be reproduced was by rotating the epiphysis posteromedially on the metaphysis. The presence and size of this peg-like tubercle was shown radiologically by CT scanning in one pair of intact adolescent femurs.