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

Polyimide (MP-1, MMATech, Haifa, Israel), is a high performance aerospace thermoplastic used for its lubricity, stability, inertness and radiation resistance. A wear resistant thin robust bearing is needed for total hip arthroplasty (THR). After independent laboratory testing, in 2006, the author used the material as a bearing in two Reflection (Smith and Nephew, USA) hip surgeries. The first, a revision for polyethylene wear, survives with no evidence of wear, noise, new osteolysis or complications related to the MP-1 bearing after 16 yrs. The second donated his asymptomatic MP-1 hip at 6.5yrs for post-mortem examination. There were no osteoclasts, cellular reaction bland in contrast to that of polyethylene. In 2013 a clinical study with ethical committee approval was started using a Biolox Delta (Ceramtec, Germany) head against a polyimide liner in 97 patients. MMATech sold all liners, irradiated: steam 52:45. Sixteen were re-machined in New Zealand. Acetabular shells were Delta PF (LIMA, Italy). The liner locked by taper. The cohort consisted of 46:51 M:F, and ages 43 to 85, mean 65. Ten received cemented stems. For contralateral surgery, a ceramic or polyethylene liner was used. Initial patients were lower demand, later, more active patients, mountain-biking and running. All patients have on-going follow up, including MP-1 liner revision cases. There has been no measurable wear, or osteolysis around the acetabular components using weight-bearing radiographs. Squeaking within the first 6 weeks was noted in 39 number of cases and subtle increase in palpable friction, (passive rotation at 50 degrees flexion), but then disappeared. There were 6 revisions, four of which were related to cementless Stemsys implants (Evolutis, Italy) fixed distally with proximal linear lucencies in Gruen zones 1 and 7, and 2 and 6. No shells were revised and MP-1 liners were routinely changed to ceramic or polyethylene. The liners showed no head contact at the apex, with highly polished contact areas. There were no deep or superficial infections, but one traumatic anterior dislocation at 7 years associated with 5 mm subsidence of a non-collared stem. The initial squeaking and increased friction was due to the engineering of the liner / shell composite as implanted, not allowing adequate clearance for fluid film lubrication and contributed to by shell distortion during impaction. The revised bearings were “equatorial” rather than polar, and with lack of wear or creep this never fully resolved. Where the clearance was better, function was normal. The “slow” utilization was due to my ongoing concern with clearances not being correct. The revision of 4 Stemsys stems, tribology issues may have contributed, but non “MP-1” / Stemsys combinations outside this study have shown the same response, thought to be due to de-bonding of the hydroxyapatite coating. With correct engineering and clearances, a 3.6 mm thick MP-1 bearing, a surface Ra<0.5, steam sterilized, shows no appreciable wear, and with confidence, can be used as a high performance THR bearing

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

The need for a more durable, metal free, non-osteolytic particle generating material in Total Hip Replacement (THR) is urgently required to reduce revision surgeries. Current used materials; ceramic, metal and UHMWPE remain discrepant for long-term use. Polyimide (MP-1™) is a high performance biopolymer, originating from aerospace industry. MP-1™ is heat resistant, highly cross-linked and exhibits a self-lubrication property required for bearings and articulating joints. Being resistant to fatigue, creep and chemicals and serializable by autoclave or irradiation, MP-1™ is ideal for medical devices. Finalizing pre-clinical testing, two patients were implanted 13 years ago after informed consent. A PM (Post Mortem) retrieval at 6.5 years, showed no measureable wear, a bland synovium, and no osteoclastic or bone marrow reaction. The 13Y patients' hip, a revision from Polyethylene wear to MP-1™, has an unchanged radiograph and is fully active (Fig. 1). The Ethical Committee approved 100 patients with a single surgeon (PJB) post-marketing trial running Delta ceramic femoral ball against MP-1™ liner. Age range is from 81 to 33 years. The younger patients now being offered MP-1™, in view of the retrieval data. The MP-1™ acetabular liner is 4mm thick, as currently used in a LIMA PF shell, which replaces polyethylene, ceramic or dual mobility options. Out of the 78 enrolled patients, 52 patients have the implant for more than 5 years. The only “Complications” in a few patients was an initial squeak which spontaneously disappears by 10 days and never returns. This is likely due to reduced clearance between head and liner and likely easily correctable. There have been no dislocations or restrictions on activity level. Oxford and Harris Hip scores along with radiology, blood and clinical examination are collected during follow-up. MP-1™ liner on Delta ceramic head in THA, or in the future with MP-1 head, looks very promising with advantages of ease of sterilization, insignificant wear, no tissue reactivity and ability to have thin section and larger femoral heads if desired for larger range of motion. MP-1™ biomaterial is used for other medical devices as well such as dental implants and trauma nails, plates and screws. For any figures or tables, please contact the authors directly

Ligament balancing can be difficult to perfect in total knee arthoplasty (TKA), where current surgical practice is subjective and highly dependent on the individual surgeon. Proper ligament balancing contributes to postoperative stability, prosthetic alignment, and proprioception. Conversely, imbalance is linked to increased wear rates of the polyethylene component within the implant and, in turn, early surgical revision. With the end goal of quantification of joint compartmental pressures, pressure sensor arrays have been designed to quantify contact stresses within the knee during TKA. Flexible, capacitive pressure sensors are designed as simple parallel plates, enabling a robust solid state design. Modification of cleanroom microfabrication processes enable realization of these arrays on polyimide (common in microdevices), and polyethylene (common in joint replacements). Readout circuitry implements an Analog Devices capacitance to digital chip and output is compared to direct LCR meter data. Testing verifies the highly linear response of the sensors with applied normal loads corresponding to pressure magnitudes present in passive (intraoperative) knee flexion. Spatial resolution of the arrays is 0.5 mm, with a critical dimension of 25 micrometers, allowing the magnitude and location of forces to be accurately recorded. The MEMS pressure sensors are mounted on a tibial trial, with the body of the trial housing all circuitry. The sensors are read sequentially, and the data undergoes analog to digital conversion prior to wireless data transmission at 2.4 GHz. An Instron machine is used for compressive loading for laboratory calibration and testing. This paper outlines device fabrication, readout circuit implementation, and preliminary results

Introduction/Background: This study was designed to determine the osteoinductive capacity of rhBMP-2 in a non-critical size femoral defect in normal rats and rats with diabetes mellitus (DM). It was hypothesized that DM would result in impaired bone regeneration in the femoral non-critical size defects due to reduced bone formation and local delivery of rhBMP-2 would accelerate non-DM healing and normalize impaired bone healing in DM rats to the levels of Non-DM bone healing. Materials/Methods: A total of 80 BB Wistar rats were used in the project. A 3mm defect was created during surgery and stabilized with a polyimide plate and either a 0.05cc/11μg dose of rhBMP-2 or buffer in a collagen sponge was implanted into the defect. Microradiographs were taken on the day of sacrifice and processing of samples for PECAM-1 immunohistochemistry, histomorphometry, and mechanical testing was performed. Results: Both Non-DM and DM groups treated with rhBMP-2 demonstrated significantly higher radiographic scoring, total new bone formation, BV quantification, and mechanical testing parameters compared to those treated with buffer at all timepoints with no significance noted between Non-DM and DM groups treated with rhBMP-2. Discussion/Conclusions: This study reveals decreased amount of new bone formation in DM animals compared to Non-DM animals, showing the detrimental effects of DM upon bone healing. A single application of rhBMP-2 resulted in new bone formation in DM animals similar to Non-DM animals, suggesting a critical role for rhBMP-2 in ameliorating the deleterious effects of DM on bone regeneration and formation. Besides these groups 15 more DM rats were used for PECAM-1 staining for angiogenesis (7 with 1 loss at a 3 week time point) and mechanical testing (8 at a 9 week time point)

Purpose: Healing may be problematic after lag screw osteosynthesis of pertrochanteric fractures in osteoporotic bone due to the greater risk of defective fixation. Acrylic cement has been proposed to reinforce the fixation of the lag screw in these patients, principally to avoid the risk of cutout, but the acrylic cement’s thermal toxicity, its poor biocompatibility, and the difficult manipulation are important drawbacks. Cortoss® is a new composite biomaterial composed of bisphenol-aglycidly (bis-GMA) which could be an attractive alternative to classical cements. Cortoss is an injectable material with mechanical properties similar to human cortical bone. The purpose of this clinical study was to describe the new method for injection the material and to assess the anchoring force and safety of Cortoss in osteoporotic patients undergoing surgical fixation of pertrochanteric fractures. Material and methods: This prospective study was approved by the local ethics committee. Twenty consecutive patients aged 70 years or more with pertro-chanteric fracture were included. The lag screw was inserted under fluoroscopic guidance, and the maximum insertion torque was measured. The screw was then unscrewed seven turns (length of the threaded head), and 2.5 cm Cortoss was injected via a polyimide catheter measuring 2.5 mm in diameter. The screw was then rescrewed in place to a troque 30% above that measured without Cortoss. Results: Eighteen women and two men, age 70 – 96 years, gave their informed consent to participate in the study. Mean maximal insertion torque without Cortoss was 1.23 Nm (min 0, max 4.8 Nm), which was increased 30% with Cortoss. Posto-operative x-rays showed that the screw head was embedded in an envelope of Cortoss and that the Cortoss had diffused into the adjacent bone. There were no adverse effects. Discussion and conclusion: Cortoss provided effective reinforcement of the fixation as demonstrated by the higher insertion torque. Cortoss can also increase the mechanical resistance of the screw-cancellous bone interface, limit fixation default, and reduce secondary displacement of the lag screw in patients with osteoporotic bone. Improved stability can also reduce immobilisation time and facilitate bone healing without increasing the risk of secondary displacement and subsequent morbidity. Due to its safety, easy use, and efficacy, Cortoss provides a better alternative than acrylic cement for reinforcement of lag screw fixation of porotic bone