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

Aim of the study: The aim of this study was to explore whether adverse reactions would occur during the material’s degradation period even at a later time point after fracture healing had been completed, in metacarpal fractures treated with third generation bioabsorbable implants. Materials and Methods: 12 unstable, displaced metacarpal fractures in 10 consecutive patients (7 males, 3 females; mean age 36.4 y, range 18–75 y) were treated with third generation absorbable plates and screws (Inion. ®. OTPSTM Biodegradable Mini Plating System), where resorption is supposed to occur within 2 to 4 years. 9 patients (10 fractures) were available for follow-up (mean 25.6 months, range 14 to 44 m) and were examined both clinically and radiologically. For patients without appearance of foreign body reaction the minimum follow-up time was 24 months. Results: Fracture healing was uneventful in all cases. A foreign body reaction was observed more than a year postoperatively in 4 patients, who were subjected to surgical debridement and implant remnants removal. Histological examination confirmed the diagnosis of aseptic inflammation and foreign body reaction. 2 further patients reported a self subsiding transient local swelling. Conclusion: Our results indicate that modern absorbable implants with longer degradation period have not eliminated the problem of foreign body reaction, but simply postponed it at a later time postoperatively. Patients treated with bioabsorbable implants should be advised of this possible late complication and should be followed for at least two years, possibly longer

The aim of this study was to explore whether adverse reactions would occur during the material’s degradation period even at a later time point after surgery and whether these phenomena were clinically significant and would influence the final outcome. 12 unstable, displaced metacarpal fractures in 10 patients (7 males, 3 females; mean age 36.4 y, range 18–75 y) were treated with the Inion. ®. OTPSTM Biodegradable Mini Plating System. 9 patients (10 fractures) were available for follow-up (mean 25.6 months, range 14 to 44 m). For patients without appearance of foreign body reaction the minimum follow-up time was 24 months. Patients were examined both radiologically to evaluate fracture healing, and clinically by completing the DASH-score and a visual analogue scale for pain assessment. Grip strength, finger strength and range of motion of metacarpo-phalangeal and interphalangeal joints were measured. Fracture healing occurred uneventfully in all patients within six weeks. The most important complication was a foreign body reaction observed in 4 of our patients more than a year postoperatively. All were re-operated and had the materials removed. Histological examination confirmed the diagnosis of aseptic inflammation and foreign body reaction. Although internal fixation of metacarpal fractures by using bioabsorbable implants is a satisfactory alternative fixation method, patients should be advised of this possible late complication and should be followed postoperatively for at least one and a half year, possibly longer

A patient in his thirties developed synovitis with grade 4 chondrolysis and a stiff knee with a fixed flexion deformity between three and six years following PLC and PCL reconstruction using LARS (Ligament Augmentation and Reconstruction System, Corin). There was histologic evidence of foreign body reaction, the knee was painful, swollen and stiff. We did not use any further LARS ligaments for soft tissue reconstructions of the kneein our practice. We commenced a recall programme for all 83 patients patients who underwent a soft tissue knee reconstruction using LARS. Of those contacted, 41 replied (49%) and 16 patients had symptoms (19%) and were investigated further with XRay, MRI and arthroscopy as indicated. We discovered a total of five patients had histologically proven synovitis with foreign body reactions (6%), three of whom had life-changing symptomatic pain, swelling and stiffness with degenerate changes (3.6%). These patients had undergone various reconstructions, including a) PLC only, b) ACL and PCL, c) PCL and PLC and d) ACL, PCL and PLC. A further single case of massive bone cyst formation was noted, following PCL reconstruction using LARS (1.2%)

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 Masquelet technique is a variable method for treating critical-sized bone defects, but there is a need to develop a technique for promoting bone regeneration. In recent studies of bone fracture healing promotion, macrophage-mesenchymal stem cell (MSC) cross-talk has drawn attention. This study aimed to investigate macrophage expression in the induced membrane (IM) of the Masquelet technique using a mouse critical-sized bone defect model. The study involved a 3-mm bone defect created in the femur of mice and fixed with a mouse locking plate. The Masquelet (M) group, in which a spacer was inserted, and the Control (C) group, in which the defect was left intact, were established. Additionally, a spacer was inserted under the fascia of the back (B group) to form a membrane due to the foreign body reaction. Tissues were collected at 1, 2, and 4 weeks after surgery (n=5 in each group), and immunostaining (CD68, CD163: M1, M2 macrophage markers) and RT-qPCR were performed to investigate macrophage localization and expression in the tissues. The study found that CD68-positive cells were present in the IM of the M group at all weeks, and RT-qPCR showed the highest CD68 expression at 1 week. In addition, there was similar localization and expression of CD163. The C group showed lower expression of CD68 and CD163 than the M group at all weeks. The B group exhibited CD68-positive cells in the fibrous capsule and CD163-positive cells in the connective tissue outside the capsule, with lower expression of both markers compared to the M group at all weeks. Macrophage expression in IM in M group had different characteristics compared to C group and B group. These results suggest that the IM differs from the fibrous capsules due to the foreign body reaction, and the macrophage-MSC cross-talk may be involved in Masquelet technique

Question: Is the histopathological response of the peri-prosthetic tissue to metal-on-metal bearings comparable to the well studied reactions to polyethylene debris or do specific reactions exist and are theses reactions depending on the implant design?. Methods: Periprosthetic tissue samples from 19 THR and Hip Resurfacings (11 Birmingham Hip Resurfacings, 2 (historical)McMinn Hybrid Hip Resurfacings, 5 MetaSUL THR) with a variety of failure mechanisms were examined histopathologically and immunohistochemically. Results: Only the samples of the (historical) McMinn Hybrid resurfacings showed a stronger histiocytic foreign body reaction and a higher grade metallosis. In all other cases only a mild if any histiocytic foreign body reaction was found. Additionally a chronic lymphoplasmacellular tissue reaction was present in all cases. 3 cases showed a higher grade chronic lymphoplasmacellular inflammatory tissue response comparable to a specific immune reaction. Discussion: We found two different response mechanisms of the periprosthetic tissues to metal-on-metal bearings. In addition to the classic histiocytic foreign body reaction which was usual mild and only stronger in cases with a greater amount of metallic debris a lymphoplasmacellular inflammatory reaction usually was present but did not reach the level of inflammatory alterations associated with potential osteolysis and was not related to the implant or amount of wear. In 3 of our 19 cases the lymphoplasmacellular infiltration was stronger and comparable to a specific immune reaction. The significance of the specific immune reaction could not be further explained because a correlation to the failure mechanisms was not detectable

Recent researches indicate that both M1 and M2 macrophages play vital roles in tissue repair and foreign body reaction processes. In this study, we investigated the dynamics of M1 macrophages in the induced membrane using a mouse femur critical-sized bone defect model. The Masquelet method (M) and control (C) groups were established using C57BL/6J male mice (n=24). A 3mm-bone defect was created in the right femoral diaphysis followed by a Kirschner wire fixation, and a cement spacer was inserted into the defect in group M. In group C, the bone defect was left uninserted. Tissues around the defect were harvested at 1, 2, 4, and 6 weeks after surgery (n=3 in each group at each time point). Following Hematoxylin and eosin (HE) staining, immunohistochemical staining (IHC) was used to evaluate the CD68 expression as a marker of M1 macrophage. Iron staining was performed additionally to distinguish them from hemosiderin-phagocytosed macrophages. In group M, HE staining revealed a hematoma-like structure, and CD68-positive cells were observed between the spacer and fibroblast layer at 1 week. The number of CD68-positive cells decreased at 2 weeks, while they were observed around the new bone at 4 and 6 weeks. In group C, fibroblast infiltration and fewer CD68-positive cells were observed in the bone defect without hematoma-like structure until 2 weeks, and no CD68-positive cells were observed at 4 and 6 weeks. Iron staining showed hemosiderin deposition in the surrounding area of the new bone in both groups at 4 and 6 weeks. The location of hemosiderin deposition was different from that of macrophage aggregation. This study suggests that M1 macrophage aggregation is involved in the formation of induced membranes and osteogenesis and may be facilitated by the presence of spacers

Reducing wear of endoprosthetic implants is still an important goal in order to increase the life time of the implant. Endoprosthesis failure can be caused by many different mechanisms, such as abrasive wear, corrosion, fretting or foreign body reactions due to wear accumulation. Especially, modular junctions exhibit high wear rates and corrosion due to micromotions at the connection of the individual components. The wear generation of cobalt-chromium-molybdenum alloys (CoCrMo) is strongly influenced by the microstructure. Therefore, the aim of this work is to investigate the subsurface phase transformation by deep rolling manufacturing processes in combination with a “sub-zero” cooling strategy. We analyzed the influence on the phase structure and the mechanical properties of wrought CoCr28Mo6 alloy (ISO 5832-12) by a deep rolling manufacturing process at various temperatures (+25°C,-10°C,-35°C) and different normal forces (700N and 1400N). Surface (S. a. ,S. z. ) and subsurface characteristics (residual stress) as well as biological behavior were investigated for a potential implant application. We showed that the microstructure of CoCr28Mo6 wrought alloy changes depending on applied force and temperature. The face centered cubic (fcc) phase could be transformed to a harder hexagonal-close-packed (hcp) phase structure in the subsurface. The surface could be smoothed (up to S. a. = 0.387 µm±0.185 µm) and hardened (≥ 700 HV 0.1) at the same time. The residual stress was increased by more than 600% (n=3). As a readout for metabolic activity of MonoMac (MM6) and osteosarcoma (SaOS-2) cells a WST assay (n=3) was used. The cells showed no significant negative effect of the sub-zero manufacturing process. We showed that deep rolling in combination with an innovative cooling strategy for the manufacturing process has a great potential to improve the mechanical properties of CoCr28Mo6 wrought alloy, by subsurface hardening and phase transformation for implant applications

For chondral damage in younger patients, surgical best practice is microfracture, which involves drilling into the bone to liberate the bone marrow. This leads to a mechanically inferior fibrocartilage formed over the defect as opposed to the desired hyaline cartilage that properly withstands joint loading. While some devices have been developed to aid microfracture and enable its use in larger defects, fibrocartilage is still produced and there is no clear clinical improvement over microfracture alone in the long term. Our goal is to develop 3D printed devices, which surgeons can implant with a minimally invasive technique. The scaffolds should match the functional properties of cartilage and expose endogenous marrow cells to suitable mechanobiological stimuli in-situ, in order to promote healing of articular cartilage lesions before they progress to osteoarthritis, and rapidly restore joint health and mobility. Importantly, scaffolds should direct a physiological host reaction, instead of a foreign body reaction, associated with chronic inflammation and fibrous capsule formation, negatively influencing the regenerative outcome. Our novel silica/polytetrahydrofuran/polycaprolactone hybrids were prepared by sol-gel synthesis and scaffolds were 3D printed by direct ink writing. 3D printed hybrid scaffolds with pore channels of ~250 µm mimic the compressive behaviour of cartilage. Our results show that these scaffolds support human bone marrow stem/stromal cell (hMSC) differentiation towards chondrogenesis in vitro under hypoxic conditions to produce markers integral to articular cartilage-like matrix evaluated by immunostaining and gene expression analysis. Macroscopic and microscopic evaluation of subcutaneously implanted scaffolds in mice showed that scaffolds caused a minimal resolving inflammatory response. Our findings show that 3D printed hybrid scaffolds have the potential to support cartilage regeneration. Acknowledgements: Authors acknowledge funding provided by EPSRC grant EP/N025059/1

Screw fixation is an established method for anterior cruciate ligament (ACL) reconstruction, although with a high rate of implant-related complications. An allograft system for implant fixation in ACL reconstruction, the Shark Screw ACL (surgebright GmbH) could overcome some of the shortcomings of bioabsorbable screws, such as foreign body reaction, need for implant removal and imaging artefacts. However, it needs to provide sufficient mechanical stability. Therefore, the aim of this study was to investigate the biomechanical stability, especially graft slippage, of the novel allograft system versus a conventional bioabsorbable interference screw (BioComposite Interference Screw; Arthrex Inc.) for tibial implant fixation in ACL reconstruction. Twenty-four paired human proximal tibiae (3 female, 9 male, 72.7 ± 5.6 years) underwent ACL reconstruction. The quadrupled semitendinosus and gracilis tendon graft were fixed in one specimen of each pair using the allograft fixation system Shak Screw ACL and the contralateral one using an interference screw. All specimens were cyclically loaded at 1 Hz with peak load levels monotonically increased from 50 N at a rate of 0.1 N/cycle until catastrophic failure. Relative movements of the graft versus the tibia were captured with a stereographic optical motion tracking system (Aramis SRX; GOM GmbH). The two fixation methods did not demonstrate any statistical difference in ultimate load at graft slippage (p = 0.24) or estimated survival at slippage (p = 0.06). Both, the ultimate load and estimated survival until failure were higher in the interference screw (p = 0.04, and p = 0.018, respectively). Graft displacement at ultimate load reached values of up to 7.2 mm (interference screw) and 11.3 mm (Shark Screw ACL). The allograft screw for implant fixation in ACL reconstruction showed similar behavior in terms of graft slippage compared to the conventional metal interference screw but underperformed in terms of ultimate load. However, the ultimate load may not be considered a direct indicator of clinical failure

Menisci are crucial structures for knee homeostasis: they provide increase of congruence between the articular surfaces of the distal femur and tibial plateau, bear loading, shock absorption, lubrication, and proprioception. After a meniscal lesion, the golden rule, now, is to save as much meniscus as possible: only the meniscus tissue which is identified as unrepairable should be excised and meniscal sutures find more and more indications. Several different methods have been proposed to improve meniscal healing. They include very basic techniques, such as needling, abrasion, trephination and gluing, or more complex methods, such as synovial flaps, meniscal wrapping, or the application of fibrin clots. Basic research of meniscal substitutes has also become very active in the last decades. The features needed for a meniscal scaffold are: promotion of cell migration, it should be biomimetic and biocompatible, it should resist forces applied and transmitted by the knee, it should slowly biodegrade and should be easy to handle and implant. Several materials have been tested, that can be divided into synthetic and biological. The first have the advantage to be manufactured with the desired shapes and sizes and with precise porosity dimension and biomechanical characteristics. To date, the most common polymers are polylactic acid (PGA); poly-(L)-lactic acid (PLLA); poly- (lactic-co-glycolic acid) (PLGA); polyurethane (PU); polyester carbon and polycaprolactone (PCL). The possible complications, more common in synthetic than natural polymers are poor cell adhesion and the possibility of developing a foreign body reaction or aseptic inflammation, leading to alter the joint architecture and consequently to worsen the functional outcomes. The biological materials that have been used over time are the periosteal tissue, the perichondrium, the small intestine submucosa (SIS), acellular porcine meniscal tissue, bacterial cellulose. Although these have a very high biocompatibility, some components are not suitable for tissue engineering as their conformation and mechanical properties cannot be modified. Collagen or proteoglycans are excellent candidates for meniscal engineering, as they maintain a high biocompatibility, they allow for the modification of the porosity texture and size and the adaptation to the patient meniscus shape. On the other hand, they have poor biomechanical characteristics and a more rapid degradation rate, compared to others, which could interfere with the complete replacement by the host tissue. An interesting alternative is represented by hydrogel scaffolds. Their semi-liquid nature allows for the generation of scaffolds with very precise geometries obtained from diagnostic images (i.e. MRI). Promising results have been reported with alginate and polyvinyl alcohol (PVA). Furthermore, hydrogel scaffolds can be enriched with growth factors, platelet-rich plasma (PRP) and Bone Marrow Aspirate Concentrate (BMAC). In recent years, several researchers have developed meniscal scaffolds combining different biomaterials, to optimize the mechanical and biological characteristics of each polymer. For example, biological polymers such as chitosan, collagen and gelatin allow for excellent cellular interactions, on the contrary synthetic polymers guarantee better biomechanical properties and greater reliability in the degradation time. Three-dimensional (3D) printing is a very interesting method for meniscus repair because it allows for a patient-specific customization of the scaffolds. The optimal scaffold should be characterized by many biophysical and biochemical properties as well as bioactivity to ensure an ECM-like microenvironment for cell survival and differentiation and restoration of the anatomical and mechanical properties of the native meniscus. The new technological advances in recent years, such as 3D bioprinting and mesenchymal stem cells management will probably lead to an acceleration in the design, development, and validation of new and effective meniscal substitutes

Millions of medical devices made of synthetic or modified natural materials all trigger a similar reaction—the foreign body reaction. Biocompatibility, for materials that pass routine cytoxicity assays, is largely associated with a mild foreign body reaction. I.e. a thin, avacular, collagenous, non-adherent foreign body capsule. The implant is incorporated into a dead-zone of acellular scar. The contemporary tissue engineering paradigm would suggest that synthetic polymers and scaffolds lacking cellular, biomolecule or biomimetic elements will give this same fibrotic, avascular healing reaction. In this talk, a synthetic biomaterial will be described that readily integrates into tissue and may stimulate spontaneous reconstruction of tissue. The material is fabricated by a process called sphere-templating and it can be made from many synthetic polymers including hydrogels, silicones and polyurethanes. All pores are identical in size and interconnected. Studies from our group have shown optimal healing (as suggested by extensive vascularity and minimal fibrosis) for spherical pores of 30–40 m size. The integrative healing noted is independent of biomaterial. Similar results are observed with sphere-templated silicone rubber and pHEMA hydrogel. In addition, surface chemical modification of the hydrogel with carbonyl diimidazole, or immobilisation on the hydrogel of collagen I or laminin did not change the healing response. Also, good healing results have been seen upon implantation in skin (subcutaneous, percutaneous), heart muscle, sclera, skeletal muscle, bone and vaginal wall. We consistently find the pore spaces heavily populated by monocytic cells that stain for macrophage cell surface markers. However, at long implantation times (16 or more weeks), the ability to stain for macrophage surface markers decreases. It could be possible that these cells populating the implants are differentiating into other tissues. Thus, such materials may represent a path to cell-free tissue engineering. Others have seen similar healing results, via completely different materials strategies, generally involving biological molecules. The in vivo results from our group and related results from other groups suggest we are on the cusp of a revolution in healing, biomaterials integration and tissue reconstruction. Also, the boundaries between biomaterials and tissue engineering continue to blur

Aims: Fracture repair with biodegradable implants (BDI) avoids implant removal, associated with improved patientñs beneþt and reduced health cost. However, foreign body reactions around the implants have been reported. Furthermore, data on in-vivo degradation of BDI remain limited on animal trials or human case reports. Therefore, the purposes of this prospective study were 1) to evaluate clinical and radiological results and side effects of biodegradable rods used to treat radial head fractures and 2) to assess the role of magnetic resonance imaging (MRI) to visualise BDI and their degradation. Methods: 31 displaced radial head fractures in 31 patients (median age of 30 (20–59) years) were þxed with PDLLA-rods. Clinical and radiological results were evaluated after a median follow-up of 18 (3–41) months (Broberg-Morrey score). MRI (1.5 Tesla) was applied in 14 patients. Results: The average Broberg-Morrey score was 90.5; 97% of the cases were classiþed as excellent or good, 3% as fair. Patientñs satisfaction was rated as excellent or good in 93%, as fair in 7%. No foreign body reaction was observed. In all 14 MRI cases localization, size and type of BDI were sufþciently depictable. Signiþcantly changed signal intensity, potentially representing material degradation, was not observed throughout a maximal follow-up interval of three years. Conclusions: More than 93% excellent or good subjective and objective results conþrm the advantageous use of PDLLA-rods for þxation of radial head fractures. MRI proved to be an appropriate non-invasive method to visualise type and size of BDI, whereas signs of implant degradation have not been seen after a median F/U of 18 months

Introduction Rotator cuff degeneration is considered to be a major factor in the pathogenesis of rotator cuff tendon tear. Degenerative weakening of the rotator cuff can result in irreversible complete cuff-tear arthropathy syndrome. Recently a porcine small intestinal submucosa (SIS) has been approved by TGA as biological implant for the repair of rotator cuff tendon tear. The aims of this study are to evaluate the safety and efficacy of SIS. Methods A commercial brand of SIS was examined by histology and PCR technique. The material was implanted into mice and rabbits for the evaluation of biological reaction and inflammatory response. Next, we have used SIS to replace the rotator cuff tendon in rabbit (N=10) and compared to control (N=10). Histological examination was conducted at four and eight weeks after implantation. To further confirm if cells present in SIS material were of porcine origin, nested PCR for the amplification of DAP12 gene was used. Results Fresh SIS membrane before implantation contain multiple layers of spindle-shaped cells mixed with a small population of round-shaped cells. Chloroacetate esterase staining showed that the round-shaped cells are positive, indicating that they are mast cells. The tissue architecture of SIS mimics tendon structure as evidenced by H & E staining. The SIS membrane contained porcine DNA materials. Subcutaneous implant of SIS in mice (by six) for up to seven days showed no obvious inflammatory response or foreign body reaction. The result demonstrated that SIS has remained in the region and mixed with regenerative fibrous tissue after eight weeks. In some cases there was a massive recruitment of lymphocytes along the surface of membrane. However, no foreign body reactive giant cells were observed. Conclusions The result of this study indicated that SIS contains porcine cells and nucleic acid, which contradicts current views that SIS is a cell free biomaterial. Although no foreign body reaction of SIS was observed, SIS implant may cause chronic inflammation. Further studies should be conducted to confirm the clinical efficacy of SIS implant for rotator cuff tendon tear

[Introduction]. In 1995, Muller reported on the improvement of metal-on-metal (MOM) bearing over the existing metal-on-polyethylene (MOP) articulations which demonstrated more rapid wear together with granulomatous foreign body reactions, damage of periarticular bony and soft tissues and associated expansile psoas bursal masses. He suggested that adequate lubrication together with improved material properties and manufacturing technologies would bring to the market a superior device with greater longevity. We wish to present our experience with a modern version of a MOM bearing. [Material and Methods]. Between April 2008 and February 2012, we implanted 160 MOM THA with head diameters of 38–50 mm in 139 patients (21 males and 118 females). Their ages were 40–86 years (avg. 63.6 yrs). Follow up was 9 to 53 months post implantation (avg. 28 months). All implants were manufactured by one company (Wright Medical Technology, Arlington, TN, USA). The stems were of a standard titanium-aluminum alloy, either 45 ANCA-FIT or 115 PROFEMUR Z non-cemented stems. Acetabular components were all CONSERVE PLUS cobalt-chromium monoblock shells. Heads were also fabricated out of cobalt-chromium alloy, with modular junctions. Patients with complaints of groin pain and/or swelling or hip instability underwent MRI examination in order to detect the presence of fluid collections or soft tissue masses (Fig. 1 and 2). The statistical correlation between abnormal findings on MRI and age, gender, head diameter, component position and duration post-surgery was performed. [Results]. 27 hips in 23 patients (16.9%) were found to have either a fluid collection or “pseudotumor”. These were in 2 males and 21 female patients. There were 19 males and 97 females without complaints who did not undergo MRI examination. There was no difference in age between these two groups of patients (63.1 vs. 63.7 yrs). There was no difference in duration from the time of implantation, but there was an early presentation of symptomatic pseudotumor. There appeared to be a significant difference between the mean head diameter of the two groups, 41.8 mm and 44.2 mm respectively. There was no statistical difference between the two groups with regard to implant orientation: cup inclination 18–70 degrees (40.4 vs. 43.8 degrees); cup anteversion −13−49 degrees (14.0 vs. 15.0 degrees); stem anteversion 2–48 degrees (20.2 vs. 23.1 degrees); and stem offset 17.5–56.2 mm (38.2 vs. 37.8 mm). [Discussion]. In this study, it is important to emphasize that the appearance of symptoms and development of a pseudotumor occurred early after a MOM THA in some patients. It may represent a hypersensitivity to materials implanted. However, the possibility that this may represent a foreign body reaction to particulate debris produced by articulating surfaces much like that seen with alternative material such as MOP, reflective of wear, insufficient lubrication or other causes. In this regard, our study suffers from the limitation that serum levels of chromium and cobalt were not obtained from symptomatic patients. Nor were these patients skin tested for hypersensitivity to these materials. Also it will be important to subject all patients to MRI examination to evaluate the possibility of “silent” fluid collections and pseudotumors

Introduction: Hip simulator tests, analyses of retrieved components as well as radiostereometric measurements revealed that cups made of highly linked polyethylene show a much better wear performance than cups of conventional polyethylene. However, to the best of our knowledge, histomorphological studies of tissues from the surrounding of highly cross – linked polyethylene components have not been reported yet. The aim of this study was to examine such tissues for particles, released from highly cross – linked polyethylene cups and to compare the findings with those of conventional polyethylene. Material and methods: So far, periprosthetic tissues retrieved at revisions of 11 total hip endoprostheses with highly cross – linked polyethylene cups could be analysed. The revisions became necessary 3 to 50 months after implantation because of cup loosening (4), stem loosening (1), infection (3), periprosthetic fracture of the femur (1), multiple dislocations (1) and periarticular ossification (1). The findings were compared with those of 5 artificial joints (2 ABG, 2 Müller Cup older design, 1 Metalback pressfit) with conventional polyethylene cups and 54 to 231 months of function. 5 μm sections were made from the tissues and conventionally stained with HE and van Gieson. Morphometric measurements were done using objectives 10 and 40 of an Olympus microscope and the ‘Analysis’ program of Soft Ware Imaging GmbH. In the Durasul TM – cases, the total amount and the total area of particles were ascertained while in the cases used for comparison only random CX 40 samples could be measured because of the much higher content of particles. Results: The DurasulTM cases showed in contrast to the cases with conventional polyethylene cups, no distinct foreign body reaction. In four of the DurasulTM cases no particles could be detected at all and in the remaining seven particles could be found only in a few areas. Their number per section was between 6 and 1208, their total area per mm. 2. section ranged between 0,03 and 6,99 × 10 5.mm. 2. In the conventional polyethylene cases the number of particles per section was between 2832 and 71447, their total area per mm. 2. section ranged between 1,06 and 25,91 × 10 3mm. 2. ! The average size of the DurasulTM particles was clearly bigger than the size of the conventional Polyethylene. Discussion: The measurements in tissues of early revisions show that DurasulTM releases much less particles into the surrounding than PE and cause rather no foreign body reaction. Accordingly, the burden of the tissue with polyethylene debris is much lower while the particle size is bigger with DurasulTM than with PE

Introduction: It is well known that the fate of biomaterials is determined by the distribution of proteins attached to the surface from the initial contact with blood or serum. This profile determines wether a material is inert, creates a foreign body response or is bioactive. Bioinert materials, such as polyethylene completely denature surface proteins, whilst materials inducing inflammatory responses are predisposed to complement protein attachment. Bioactive materials such autologous tissue grafts adsorb, but do not denature serum proteins such as fibronectin and Von Willebrand’s factor. This does not interfere with the healing cascade. This aim of this study is to prepare a synthetic bone graft substitute that activates the body’s autologous healing cascade by activating platelets, without activating a complement response through the controlled adsorption of serum proteins. Methods: Polymers composed of varied concentration of acrylic acid (AA) and comonomers (methyl, ethyl and butyl methacrylates (MMA, EMA, BMA)) were prepared in glass vials by free radical polymerisation. Fresh blood was collected from a healthy donor and pipetted immediately into each chamber. Glass was used as a control. The chambers were incubated at 37o C for 2 hours. The surface morphology was examined using Scanning Electron Microscopy (SEM). Concentration of complement protein C5a and prothrombin fragments 1 and 2 were determined using commercial ELISA kits. Foreign body reaction (FBR) initiated by the biomaterial was estimated by counting leukocytes on clot sections using immunofluorescence. Results: Extent of coagulation was correlated with plasma concentrations of Prothrombin fragments 1 and 2. These measurements show blood incubated with various polymers composed of different comonomers all promoted the formation of blood clots. It was found that the leukocyte population towards the interface of clot and polymer (AA:MMA) decreased with increasing surface acid concentration (65%AA:MMA 30 leukocytes/0.25mm2, glass 70 leukocytes/0.25mm2 (p< 0.05)). FBR is induced by the activation of complement system. The percentage of C5a concentration detected in blood incubated with various polymers composed of different comonomers relative to normal serum level of C5a (35ng/mL). No significant elevations of C5a were measured from polymer 65% AA:MMA and 65% AA:EMA. Glass induced vigorous complement response as expected. The synergistic combination of surface acid concentration and comonomers had a significant effect on extent of FBR. Increased acid concentration resulted in decreased C5a level with MMA and ET but increased level with BMA. Discussion: The functional groups exposed on the surface of a material influence whether leukocyte or platelet activation is responsible for the subsequent physiological response. By modifying the combinations of surface acid concentrations and comonomers, we show that a biomaterial with an appropriate surface chemistry promotes the platelet plug formation and coagulation but down regulated foreign body reaction. This study shows that that a biomaterial with the appropriate surface chemistry to evoke the same coagulation response as damaged tissue, mediated through platelet activation and intrinsic and extrinsic coagulation, initiates the initial pathways of the bone healing cascade. This material is a realistic candidate for biomaterial induced bone regeneration

Ceramic-on-ceramic bearing is an attractive alternative to metal-on-polyethylene bearing due to the unique tri-bological advantages of alumina. However, despite the long-term satisfactory results obtained so far in the vast majority of patients, failure may occur in a few cases. Clinical, radiographic, laboratory and microbiological data of 30 consecutive subjects with failed alumina-on-alumina total hip arthroplasties (THA) were analyzed to define if foreign body reaction to wear debris may be responsible for periprosthetic bone resorption, as in conventional metal-to-polyethylene bearings. In all cases, clinical and radiographical material was reviewed, retrieved implants were examined, and histology of periprosthetic tissues was analyzed. Massive osteolysis was never observed. Apart from 5 five patients for which revision surgery was necessary due to the occurrence of late infection, in all other cases failure had occurred due to secondary implant instability (as in the case of screwed sockets, 19 cases) or to malpositioning of the implant (5 cases). One patient suffered from chronic dislocation. In the vast majority of cases, ceramic wear debris was absent or scarce, and did not induce any tissue reaction. In a few cases with severe wear, debris was evident in clusters of perivascular macrophages, notably in the absence of foreign body multinucleated cells, confirming the excellent biocompatibility of ceramics. These findings indicate that wear debris and peri-prostetic bone resorption were the effect rather than the cause of failure, differently from revised metal-on-polyethylene bearings, in which foreign body cell reaction is the main pathogenetic mechanism of failure. On the contrary, mechanical problems, due to incorrect surgical technique or to inadequate prosthetic design, may cause instability of the implant, in turn resulting in wear debris production and moderate if any biological reaction

The retear of the rotator cuff (RC) repair is a significant problem. Usually it is the effect of poor quality of the tendon. The aim was to evaluate histologically two types of RC reconstruction with scaffold. We have chosen commercially available scaffold polycaprolactone based poly(urethane urea). Rat model of supraspinatus tendon injury was chosen. There were four study groups: RC tear (no repair) (n=10), RC repair (n=10), RC repair augmented with scaffold (n=10) and RC reconstruction with scaffold interposition between tendon and bone (n=10). The repairs were investigated histologically at 6 and 16 weeks. The results in two groups in which scaffold was used had significantly better scores at 6 weeks comparing to non-scaffold groups (16,4±3, 17,3± 2,8 vs. 12,5±4,4, 13,8±1,4 respectively) and 16 weeks (23±1,9, 22,8±1,6 vs. 13,8±3,3, 14,9± 3,8 respectively). Results in two scaffold groups improved between 6 and 16 weeks. Signs of foreign body reaction against scaffold were not observed. Application of scaffold to strengthen the repair site and bridging of the tendon defect improved healing of the RC repair in animal model at 6 and 16 weeks. The quality of reconstructed tendon improved over time. No such effect was observed in groups without repairs and isolated repairs were performed