Inflammatory tissue response in human soft tissue is caused by a higher particle load near carbon fiber-reinforced PEEK compared to titanium plates.

Titanium as the leading implant material in locked plating is challenged by polymers such as carbon fiber-reinforced polyetheretherketone (CFR-PEEK), which became the focus of interest of researchers and manufacturers in recent years. However, data on human tissue response to these new implant materials are rare. Osteosynthesis plates and peri­implant soft tissue samples of 16 healed proximal humerus fractures were examined (n = 8 CFR-PEEK, n = 8 titanium). Soft tissue was analyzed by immunohistochemistry and µCT. The entrapped foreign bodies were further examined for their material composition by FTIR. To gain insight into their origin and formation mechanism, explanted and new plates were evaluated by SEM, EDX, profilometry and HR-CT. In the peri­implant soft tissue of the CFR-PEEK plates, an inflammatory tissue reaction was detected. Tissues contained foreign bodies, which could be identified as tantalum wires, carbon fiber fragments and PEEK particles. Titanium particles were also found in the peri­implant soft tissue of the titanium plates but showed a less intense surrounding tissue inflammation in immunohistochemistry. The surface of explanted CFR-PEEK plates was rougher and showed exposed and broken carbon fibers as well as protruding and deformed tantalum wires, especially in used screw holes, whereas scratches were identified on the titanium plate surfaces. Particles were present in the peri­implant soft tissue neighboring both implant materials and could be clearly assigned to the plate material. Particles from both plate materials caused detectable tissue inflammation, with more inflammatory cells found in soft tissue over CFR-PEEK plates than over titanium plates. STATEMENT OF SIGNIFICANCE: Osteosynthesis plates are ubiquitously used in various medical specialties for the reconstruction of bone fractures and defects and are therefore indispensable for trauma surgeons, ENT specialists and many others. The leading implant material are metals such as titanium, but recently implants made of polymers such as carbon fiber-reinforced polyetheretherketone (CFR-PEEK) have become increasingly popular. However, little is known about human tissue reaction and particle generation related to these new implant types. To clarify this question, 16 osteosynthesis plates (n = 8 titanium and n = 8 CFR-PEEK) and the overlying soft tissue were analyzed regarding particle occurrence and tissue inflammation. Tissue inflammation is clinically relevant for the development of scar tissue, which is discussed to cause movement restrictions and thus contributes significantly to patient outcome.

Functional outcomes before and after implant removal in patients with posttraumatic shoulder stiffness and healed proximal humerus fractures: does implant material (PEEK vs. titanium) have an impact? - a pilot study.

BACKGROUND: Posttraumatic shoulder stiffness remains a problem after proximal humerus fracture (PHF) despite good healing rates. The aim of this pilot study was to determine whether the implant material and overlying soft tissue have an effect on shoulder range of motion (ROM) before and after implant removal (IR). METHODS: 16 patients (mean age 55.2 ± 15.3 (SD) years; 62.5% female) were included who underwent operative treatment with locking plates of either carbon fiber reinforced Polyetheretherketone (PEEK) (PEEKPower® humeral fracture plate, Arthrex, Naples, Florida, USA, n = 8) or titanium alloy (Ti) (Philos®, DePuy Synthes, Johnson & Johnson Medical, Raynham, Massachusetts, USA, n = 8) for PHF. All patients presented with a limited ROM and persistent pain in everyday life after the fracture had healed, whereupon IR was indicated. ROM before and after IR were compared as well as the Constant Score (CS) and the CS compared to the contralateral shoulder (%CS) 1 year after IR. RESULTS: In group PEEK, elevation was 116.3° ± 19.2° pre- and 129.4° ± 23.7° post-IR (p = 0.027). External rotation was 35.0° ± 7.6° pre- and 50.6° ± 21.8° post-IR (p = 0.041). External rotation with the humerus abducted 90° was 38.8° ± 18.1° pre- and 52.5° ± 25.5° post-IR (p = 0.024). In group Ti, elevation was 110.0° ± 34.6° pre- and 133.8° ± 31.1° post-IR (p = 0.011). External rotation with the humerus at rest was 33.8° ± 23.1° pre- and 48.8° ± 18.7° post-IR (p = 0.048). External rotation with the humerus abducted 90° was 40.0° ± 31.6° pre- and 52.5° ± 22.5° post-IR (p = 0.011). Comparison of the two implant materials showed no significant difference. The overall CS was 90.3 ± 8.8, the %CS was 91.8% ± 14.7%. CONCLUSION: There was no significant difference in ROM, CS and %CS with respect to plate materials, although lower cell adhesion is reported for the hydrophobic PEEK. However, all patients showed improved functional outcomes after IR in this pilot study. In patients with shoulder stiffness following locked plating for PHF, implants should be removed and open arthrolysis should be performed, independently from the hardware material. LEVEL OF EVIDENCE: II.

Influence of steel implant surface microtopography on soft and hard tissue integration.

After implantation of an internal fracture fixation device, blood contacts the surface, followed by protein adsorption, resulting in either soft-tissue adhesion or matrix adhesion and mineralization. Without protein adsorption and cell adhesion under the presence of micro-motion, fibrous capsule formation can occur, often surrounding a liquid filled void at the implant-tissue interface. Clinically, fibrous capsule formation is more prevalent with electropolished stainless steel (EPSS) plates than with current commercially pure titanium (cpTi) plates. We hypothesize that this is due to lack of micro-discontinuities on the standard EPSS plates. To test our hypothesis, four EPSS experimental surfaces with varying microtopographies were produced and characterized for morphology using the scanning electron microscope, quantitative roughness analysis using laser profilometry and chemical analysis using X-ray photoelectron spectroscopy. Clinically used EPSS (smooth) and cpTi (microrough) were included as controls. Six plates of each type were randomly implanted, one on both the left and right intact tibia of 18 white New Zealand rabbits for 12 weeks, to allow for a surface interface study. The results demonstrate that the micro-discontinuities on the upper surface of internal steel fixation plates reduced the presence of liquid filled voids within soft-tissue capsules. The micro-discontinuities on the plate under-surface increased bony integration without the presence of fibrous tissue interface. These results support the hypothesis that the fibrous capsule and the liquid filled void formation occurs mainly due to lack of micro-discontinuities on the polished smooth steel plates and that bony integration is increased to surfaces with higher amounts of micro-discontinuities. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 705-715, 2018.

Surface-enrichment with hydroxyapatite nanoparticles in stereolithography-fabricated composite polymer scaffolds promotes bone repair.

Fabrication of composite scaffolds using stereolithography (SLA) for bone tissue engineering has shown great promises. However, in order to trigger effective bone formation and implant integration, exogenous growth factors are commonly combined to scaffold materials. In this study, we fabricated biodegradable composite scaffolds using SLA and endowed them with osteopromotive properties in the absence of biologics. First we prepared photo-crosslinkable poly(trimethylene carbonate) (PTMC) resins containing 20 and 40wt% of hydroxyapatite (HA) nanoparticles and fabricated scaffolds with controlled macro-architecture. Then, we conducted experiments to investigate how the incorporation of HA in photo-crosslinked PTMC matrices improved human bone marrow stem cells osteogenic differentiation in vitro and kinetic of bone healing in vivo. We observed that bone regeneration was significantly improved using composite scaffolds containing as low as 20wt% of HA, along with difference in terms of osteogenesis and degree of implant osseointegration. Further investigations revealed that SLA process was responsible for the formation of a rich microscale layer of HA corralling scaffolds. To summarize, this work is of substantial importance as it shows how the fabrication of hierarchical biomaterials via surface-enrichment of functional HA nanoparticles in composite polymer stereolithographic structures could impact in vitro and in vivo osteogenesis. STATEMENT OF SIGNIFICANCE: This study reports for the first time the enhance osteopromotion of composite biomaterials, with controlled macro-architecture and microscale distribution of hydroxyapatite particles, manufactured by stereolithography. In this process, the hydroxyapatite particles are not only embedded into an erodible polymer matrix, as reported so far in the literature, but concentrated at the surface of the structures. This leads to robust in vivo bone formation at low concentration of hydroxyapatite. The reported 3D self-corralling composite architecture provides significant opportunities to develop functional biomaterials for bone repair and tissue engineering.

Pericyte plasticity - comparative investigation of the angiogenic and multilineage potential of pericytes from different human tissues.

Pericyte recruitment is essential for the stability of newly formed vessels. It was also suggested that pericytes represent common ancestor cells giving rise to mesenchymal stem cells (MSCs) in the adult. Here, we systematically investigated pericytes and MSCs from different human tissues in terms of their angiogenic and multilineage differentiation potential in vitro in order to assess the suitability of the different cell types for the regeneration of vascularised tissues. Magnetic-activated cell sorting (MACS®) was used to enrich CD34-CD146+ pericytes from adipose tissue (AT) and bone marrow (BM). The multilineage potential of pericytes was assessed by testing their capability to differentiate towards osteogenic, adipogenic and chondrogenic lineage in vitro. Pericytes and endothelial cells were co-seeded on Matrigel™ and the formation of tube-like structures was examined to study the angiogenic potential of pericytes. MSCs from AT and BM were used as controls. CD34-CD146+ cells were successfully enriched from AT and BM. Only BM-derived cells exhibited trilineage differentiation potential. AT-derived cells displayed poor chondrogenic differentiation upon stimulation with transforming growth factor-ß1. Interestingly, osteogenic differentiation was more efficient in AT-PC and BM-PC compared to the respective full MSC population. Matrigel™ assays revealed that pericytes from all tissues integrated into tube-like structures. We show that MACS®-enriched pericytes from BM and AT have the potential to regenerate tissues of different mesenchymal lineages and support neovascularisation. MACS® represents a simple enrichment strategy of cells, which is of particular interest for clinical application. Finally, our results suggest that the regenerative potential of pericytes depends on their tissue origin, which is an important consideration for future studies.

Stress-shielding induced bone remodeling in cementless shoulder resurfacing arthroplasty: a finite element analysis and in vivo results.

Cementless surface replacement arthroplasty (CSRA) of the shoulder was designed to preserve the individual anatomy and humeral bone stock. A matter of concern in resurfacing implants remains the stress shielding and bone remodeling processes. The bone remodeling processes of two different CSRA fixation designs, conical-crown (Epoca RH) and central-stem (Copeland), were studied by three-dimensional (3-D) finite element analysis (FEA) as well as evaluation of contact radiographs from human CSRA retrievals. FEA included one native humerus model with a normal and one with a reduced bone stock quality. Compressive strains were evaluated before and after virtual CSRA implantation and the results were then compared to the bone remodeling and stress-shielding pattern of eight human CSRA retrievals (Epoca RH n=4 and Copeland n=4). FEA revealed for both bone stock models increased compressive strains at the stem and outer implant rim for both CSRA designs indicating an increased bone formation at those locations. Unloading of the bone was seen for both designs under the central implant shell (conical-crown 50-85%, central-stem 31-93%) indicating high bone resorption. Those effects appeared more pronounced for the reduced than for the normal bone stock model. The assumptions of the FEA were confirmed in the CSRA retrieval analysis which showed bone apposition at the outer implant rim and stems with highly reduced bone stock below the central implant shell. Overall, clear signs of stress shielding were observed for both CSRAs designs in the in vitro FEA and human retrieval analysis. Especially in the central part of both implant designs the bone stock was highly resorbed. The impact of these bone remodeling processes on the clinical outcome as well as long-term stability requires further evaluation.

Comparison of imaging methods used for dental implant osseous integration assessment.

Two different imaging techniques used to determine bone tissue response to dental implants were compared. Dental implants were implanted into the maxillae of 18 pigs, which were sacrificed after 4, 8 and 12 weeks. Implants with surrounding bone tissue were retrieved for methyl methacrylate histology and contact radiography. On identical sections peri-implant bone density and bone implant contact (BIC) ratio were assessed with two different imaging methods. Evaluation of Giemsa eosin stained and contact radiographed sections showed direct osseous integration for all implants and both methods showed a strong correlation with correlation coefficient r = 0.930 (P < 0.0001) for peri-implant bone density and r = 0.817 (P < 0.0001) for bone implant contact ratio. While the two imaging methods showed moderate differences for peri-implant bone density there were significant differences between the BIC values determined. In general, contact radiography tends to underestimate BIC for approximately 4.5 % (P = 0.00003).

In vivo performance of zirconia and titanium implants: a histomorphometric study in mini pig maxillae.

OBJECTIVES: To compare the bone tissue response to surface-modified zirconia (ZrO2 ) and titanium implants. METHODS: Cylindrical low-pressure injection moulded zirconia (ZrO2 ) implants were produced with an acid-etched surface. Titanium implants with identical shape, sandblasted and acid-etched surface (SLA) served as controls. Eighteen adult miniature pigs received both implant types in the maxilla 6 months after extraction of the canines and incisors. The animals were euthanized after 4, 8 and 12 weeks and 16 zirconia and 18 titanium implants with the surrounding tissue were retrieved, embedded in methylmethacrylate and stained with Giemsa-Eosin. The stained sections were digitized and histomorphometrically analysed with regard to peri-implant bone density (bone volume/total volume) and bone-implant contact (BIC) ratio. Statistical analysis was performed using Mann-Whitney' U-test. RESULTS: Histomorphometrical analysis showed direct osseous integration for both materials. ZrO2 implants revealed mean peri-implant bone density values of 60.4% (SD ± 9.9) at 4 weeks, 65.4% (SD ± 13.8) at 8 weeks, and 63.3% (SD ± 21.5) at 12 weeks after implantation, whereas Ti-SLA implants demonstrated mean values of 61.1% (SD ± 6.2), 63.6% (SD ± 6.8) and 68.2% (SD ± 5.8) at corresponding time intervals. Concerning the BIC ratio, the mean values for ZrO(2) ranged between 67.1% (SD ± 21.1) and 70% (SD ± 14.5) and for Ti-SLA between 64.7% (SD ± 9.4) and 83.7% (SD ± 10.3). For the two parameters investigated, no significant differences between both types of implants could be detected at any time point. CONCLUSION: The results indicate that there was no difference in osseointegration between ZrO2 implants and Ti-SLA controls regarding peri-implant bone density and BIC ratio.

[Comparison of regional distribution of cancellous bone in osteoporotic and non-osteoporotic distal radii]. / Vergleich der lokalen Spongiosadichte osteoporotischer und nichtosteoporotischer distaler Radii.

BACKGROUND: In cases of distal radius fractures information about the regional distribution of cancellous bone is essential for adequate fixation of osteosynthesis material. MATERIALS AND METHODS: Using quantitative computed tomography (qCT) measurements 12 distal radii were divided into 2 groups (good and bad bone quality). High-resolution CT scans were obtained at 13 locations (1-40 mm distant from radial styloid processes). The resulting cross-sections were divided into 4 quadrants and the cancellous bone density was assessed in each of them. RESULTS: In both groups regional cancellous bone density was highest immediately beneath the joint surface and decreased towards the metaphyseal region. Comparing the radial with the ulnar quadrants significant differences were found between distances of 4 mm and 12 mm from the joint surface in both groups. The comparison of the palmar and the dorsal quadrants resulted in an almost identical cancellous bone distribution. CONCLUSION: In osteoporotic distal radii cancellous bone density decrease occurs homogeneously in all regions and is least pronounced beneath the joint surface. Comparing the regional cancellous bone density (radial versus ulnar and palmar versus dorsal) significant differences were mainly found near the joint surface in both groups.

[Graft integration in the lumbar spine of bovine cancellous bone compared to autologous iliac crest in a sheep model]. / Das Einwachsverhalten von trikortikalen Beckenkammspänen und lösungsmittelkonservierter, boviner Spongiosa bei ventraler Spondylodese der Lendenwirbelsäule im Schafsmodell.

BACKGROUND: Spinal injuries are common and a standard procedure for the stabilisation of spinal injuries is ventral spondylodesis with an autograft from the iliac crest. Because of the high incidence of harvesting complications there is a need to search for alternative materials. The aim of our study was to evaluate graft integration in the lumbar spine of bovine cancellous bone compared to autologous iliac crest material. MATERIAL AND METHODS: Two groups of eight female adult sheep (median age 3 years, range 2.4-3.8 years) received surgical treatment in the form of anterior monosegmental spondylodesis. The spondylodesis was performed in all animals in the motion segment L3/4 through a lateral approach with the animals lying on their right sides. To produce serial sections, the explanted vertebral segments were implanted in methyl methacrylate. On one side the histological preparation was examined qualitatively and in addition we analysed the quantity of the bone structure with special software. RESULTS: The bone structure in both groups did not differ significantly and demonstrated integration of the grafts in the adjacent vertebral bodies. Fractures and lysis occurred in the region of the intervertebral disc and were more frequent in the group with the bovine graft. CONCLUSION: The bony integration of the grafts of both groups was not significantly different and showed good results. Almost all of the bovine grafts fractured or presented regions of lysis. In our opinion bovine cancellous bone graft is not a good alternative to autologous iliac crest.

Use of the fulcrum axis improves the accuracy of true anteroposterior radiographs of the shoulder.

In 100 patients the fulcrum axis which is the line connecting the anterior tip of the coracoid and the posterolateral angle of the acromion, was used to position true anteroposterior radiographs of the shoulder. This method was then compared with the conventional radiological technique in a further 100 patients. Three orthopaedic surgeons counted the number of images without overlap between the humeral head and glenoid and calculated the amount of the glenoid surface visible in each radiograph. The analysis was repeated for intraobserver reliability. The learning curves of both techniques were studied. The amount of free visible glenoid space was significantly higher using the fulcrum-axis method (64 vs 31) and the comparable glenoid size increased significantly (8.56 vs 6.47). Thus the accuracy of the anteroposterior radiographs of the shoulder is impaired by using this technique. The intra and interobserver reliability showed a high consistency. No learning curve was observed for either technique.

Osseointegration of zirconia and titanium dental implants: a histological and histomorphometrical study in the maxilla of pigs.

OBJECTIVES: The purpose of the present study was to histologically compare the bone tissue responses to surface-modified zirconia and titanium implants. METHODS: Threaded zirconia implants were produced using a new low-pressure injection moulding technique and thereafter surface treated by acid etching. Titanium implants with the exact shape and surface treated by sandblasting and acid etching (SLA) served as controls. Fifteen adult pigs received both implant types in the maxilla 6 months after extraction of the second and third incisors. The animals were sacrificed after 4, 8 and 12 weeks and 30 implants with surrounding bone were retrieved. RESULTS: Histological evaluation showed osseous integration for both materials. Zirconia implants revealed mean peri-implant bone density values of 42.3% (SD +/- 14.5) at 4 weeks, 52.6% (SD +/- 5.7) at 8 weeks and 54.6% (SD +/- 11.5) at 12 weeks after implantation, whereas Ti-SLA implants demonstrated mean values of 29% (SD +/- 10), 44.1% (SD +/- 18) and 51.6% (SD +/- 8.6) at corresponding time intervals. With respect to the bone-implant contact ratio, the mean values for zirconia ranged between 27.1% (SD +/- 3.5) and 51.1% (SD +/- 12.4) and for Ti-SLA, it ranged between 23.5% (SD +/- 7.5) and 58.5% (SD +/- 11.4). For the parameters investigated, no statistically significant differences between both types of implants could be detected at any time point. CONCLUSIONS: No statistical difference between implants could be demonstrated with any of the methods used. The limited number of animals per group, however, does not allow to conclude that there is no difference in osseointegration between the two types of implants, although the data tend to suggest such a trend.

An immunohistochemical study of the triangular fibrocartilage complex of the wrist: regional variations in cartilage phenotype.

The triangular fibrocartilage complex (TFCC) transmits load from the wrist to the ulna and stabilizes the distal radioulnar joint. Damage to it is a major cause of wrist pain. Although its basic structure is well established, little is known of its molecular composition. We have analysed the immunohistochemical labelling pattern of the extracellular matrix of the articular disc and the meniscal homologue of the TFCC in nine elderly individuals (age range 69-96 years), using a panel of monoclonal antibodies directed against collagens, glycosaminoglycans, proteoglycans and cartilage oligomeric matrix protein (COMP). Although many of the molecules (types I, III and VI collagen, chondroitin 4 sulphate, dermatan sulphate and keratan sulphate, the oversulphated epitope of chondroitin 6 sulphate, versican and COMP) were found in all parts of the TFCC, aggrecan, link protein and type II collagen were restricted to the articular disc and to entheses. They were thus not a feature of the meniscal homologue. The shift in tissue phenotype within the TFCC, from a fibrocartilaginous articular disc to a more fibrous meniscal homologue, correlates with biomechanical data suggesting that the radial region is stiff and subject to considerable stress concentration. The presence of aggrecan, link protein and type II collagen in the articular disc could explain why the TFCC is destroyed in rheumatoid arthritis, given that it has been suggested that autoimmunity to these antigens results in the destruction of articular cartilage. The differential distribution of aggrecan within the TFCC is likely to be reflected by regional differences in water content and mobility on the radial and ulnar side. This needs to be taken into account in the design of improved MRI protocols for visualizing this ulnocarpal complex of the wrist.

[Systemic spread of wear debris--an in-vivo study]. / In-vivo-Analyse zur systemischen Verteilung von metallischen Abriebpartikeln.

AIM: The aim of this study was to elucidate whether there is a systemic spread of wear debris from peripherally applied stainless steel and titanium particles into the blood and subsequently to parenchymatous organs. Furthermore, we report on histological findings at the implantation site. METHOD: In Syrian Gold hamsters we implanted 2 mm3 wear debris of stainless steel and titanium into the dorsal skin fold chamber. Over a period of 2 weeks we took blood samples and afterwards explanted the implant area, the heart, lung, liver and spleen. One half of the organs and the implant area were used for histological analysis. The other half of the organs and the blood samples were analysed by optical emission spectrometer with inductively coupled plasma and graphite furnace atomic absorption spectrophotometry for their contents of chromium, nickel and titanium. RESULTS: In the group with titanium particles, histological analysis of the implant site showed moderate phagocyted wear in granulocytes but no other pathological findings. Animals treated with stainless steel wear debris had a massive inflammatory reaction, in some cases leading to necrosis. The analysis of the blood and one half of the organs showed increased levels of chromium and, already 24 hours after implantation, raised values for nickel. The result of the hamsters treated with titanium showed significantly elevated levels of titanium ions in the organs, but not in the blood samples. Histology of the organs did not reveal pathological findings. CONCLUSION: In this study we could show a massive inflammatory reaction for stainless steel wear debris in contrast to titanium wear debris at the implantation site. The elevated blood levels of chromium and increased values of other metals in the organs suggest the haematogenic distribution of ions from the peripherally implanted wear debris.