Wear of the polyethylene (PE) bearing surface and wear particle-induced osteolysis (bone resorption) can lead to failure of modular total knee replacements and make expensive revision surgery necessary. Gamma-in-air sterilization of the PE insert and having a modular tibial component are both risk factors for excessive backside wear that contribute to osteolysis and implant failure. The overall wear (backside and topside) of modular total knee replacements has been subjected to considerable research in order to avoid such implant failure. The investigations reported in the present thesis evaluated both the clinical and in vitro wear performance of modular total knee replacements. The clinical investigations included damage assessment of retrieved PE inserts. A semi-quantitative grading method was developed and used to assess backside surface damage on 52 PE inserts retrieved from contemporary total knee replacement surgeries. Statistical analyses, such as univariate and multiple linear regression analysis, were performed to identify factors that influence backside damage including implant design features and patient characteristics. The damage features on the retrieved tibial PE inserts were also assessed with surface characterization techniques, such as scanning electron microscopy, energy dispersive X-ray analysis, and surface profilometry. To reduce surface damage and thus wear, PE inserts should be either gas-plasma or ethylene-oxide sterilized, used with polished tibial trays and held in place with a partial-peripheral locking mechanism. Synovial fluid samples were aspirated from a total of twenty patients and some basic biochemical analyses were performed. The total protein concentration, protein constituent fractions, the level of osmolality, and trace element concentrations were measured and compared with the same characteristics of four serum lubricants that were frequently used in simulator wear testing to mimic synovial fluid. In vitro investigations were conducted to explore the effects of some major constituents of the serum lubricants on the wear rate using a knee simulator apparatus. Increased protein constituent degradation led to increased wear. Such findings suggested that a protein layer acted as a boundary lubricant to protect the PE surfaces of knee implants. The protein constituent fractions of alpha calf serum (ACS) were similar to those measured for synovial fluid. These ACS lubricants were used in further wear studies in which hyaluronic acid (HA) and phosphate buffer solution (PBS) were successively added. The PBS was used in place of the distilled water to generate a serum lubricant with a clinically relevant level of osmolality. The thermal stability of the ACS lubricants and synovial fluid were measured. The thermal stability of the ACS lubricant that contained HA and PBS was about the same as that of human synovial fluid. The simulator wear rate of PE was significantly influenced by both HA and PBS. In further investigations, sodium azide, which has been used to inhibit microbial growth in simulator wear testing, was shown to be highly ineffective. Microbial contamination was recognized and the organism responsible was identified using standard microbiological methods. The use of an antibiotic-antimycotic mixture as the microbial inhibitor in the ACS + PBS + HA lubricant created a sterile environment and thus very clinically relevant environment for wear testing. The content of this thesis represents a comprehensive data collection on retrieval analysis and lubricant-specific knee simulator wear testing of modular total knee replacements. A more clinically relevant lubricant composition for simulator wear testing was proposed (U.S. patent Serial number 60/899,894; pending since February 9th, 2007) that improved upon the current guideline from the International Standards Organization for knee simulator wear testing. The present thesis should serve as a guide for the surgeon, researcher and the implant manufacturer to evaluate retrieved implant components and to select lubricant additives for wear testing that closely mimics the in vivo wear conditions.

The cervical spine must provide structural support for the head, allow large range of motion and protect both the spinal cord and branching nerves. There are two types of spinal joints: the intervertebral discs which are flexible connections and the facets, which are articulating synovial joints. Both types degenerate with age. Current surgical treatments include spinal fusion and articulating disc replacement implants. If both disc and facet joints are degenerated, fusion is the only option. In spinal fusion, the disc is removed and the adjacent vertebrae are fused which causes abnormally high stress levels in adjacent discs. In disc replacement, an articulating device is inserted to restore intervertebral motion and mimic healthy spinal kinematics. Disc arthroplasty does not significantly increase adjacent level stress but the lack of rotational constraint causes increased facet contact pressures. Thus, there is a need for a cervical total level arthroplasty system (CTLAS) that has a disc implant specifically designed to preserve the facet joints and implants for facet arthroplasty that can act independently or in-unison with the disc replacement. The conceptual design of a CTLAS implant system was proposed that would replace the disc and the facet joints. To facilitate medical imaging, PEEK (polyetheretherkeytone) was selected as the structural and bearing material. In the present thesis, multi-station pin-on-plate wear testing was initiated for pairs of unfilled (OPT) and carbon-fiber-reinforced (CFR) PEEK. Wear is important in arthroplasty implant design because wear particles can cause osteolysis leading to loosening. A variety of experiments were performed to investigate the effects of load, contact geometry and lubricant composition on wear. CFR PEEK was found to have much lower and more predictable wear than OPT PEEK in the present experiments. The wear of OPT PEEK pairs showed sensitivity to lubricant protein concentration. The coefficient of friction during testing was found to be quite high (up to 0.5), which might have clinical implications. Also, some subsurface fatigue was found, exposing carbon fibers of CFR PEEK. This remains a concern for its long-term application. Further wear testing is recommended using actual implants in a spine wear simulator.

There are more than 150,000 anterior cruciate ligament reconstructions each year with the goal of recovering the balance between knee stability and mobility. As many as 25 percent of these procedures will end in joint instability that can cause further damage. The risk of developing degenerative joint disease (DJD) increases in patients with previous knee injury, resulting in a higher instance of total knee arthroplasty (TKA). There are more than 400,000 TKA procedures each year, but the waiting lists for this surgery shows that many more patients are hoping to undergo this procedure. TKA provides improved knee function and pain relief for patients suffering from DJD. Although this procedure is considered successful, as younger patients undergo this treatment, the long-term performance must be improved. Major mechanisms of failure include component loosening from stress-shielding, poor integration of the implant with native tissue, and ion release from the implant. TiNb alloys are more biocompatible than currently used alloys, such as NiTi, and have mechanical properties closer to bone, so they would reduce the instance of stress shielding. TiNb can be made porous for better integration with the native bone and has superior corrosion resistance than NiTi. Engineered ligaments have generally failed to achieve mechanical properties sufficiently similar to their native counterparts, but also lack the osteochondral interface critical to the transfer of load between ligament and bone. The osteochondral interface could be incorporated through a gradient of inorganic content toward the bony insertion ends of the ligament graft, as we showed that in increase of inorganic content resulted in the transdifferentiation of osteoblasts toward chondrocyte-like cells (bone to cartilage-like). A composite scaffold composed of an electrospun mesh with either a hydrogel component or extracellular matrix (ECM) produced by the cells may be a suitable tissue engineered ligament graft. The non-linear stress-strain behavior seen in native ligament is exhibited by both of these systems, and the ECM produced by these systems is consistent with ligament tissue. The ECM-electrospun mesh composite exhibited higher elastic modulus than the fibrin-electrospun mesh composite, but required extensive pre culture while the fibrin-electrospun mesh composite could be fabricated in situ.

Ultra-high molecular weight polyethylene (UHMWPE) is used worldwide as a bearing material in total joint replacement prostheses. Despite its excellent biocompatibility and high wear resistance, wear of UHMWPE components continues to be a major problem limiting the clinical lifespan of UHMWPE-containing orthopaedic implant devices. Multi-directional motion or cross-path motion is known to affect wear rates of UHMWPE in total knee and hip replacement prostheses. The purpose of this study was to quantify the effect of counterface roughness on the cross-path wear of UHMWPE and to determine if the previously established unified theory of wear model could accurately predict wear rates in an abrasive wear environment. UHMWPE pins were articulated against both smooth (centerline roughness, Ra, of 0.015 µm) and rough (Ra = 0.450µm) cobalt-chromium counterfaces in a series of six rectangular wear paths (width = A, length = B) with systematically increasing aspect ratios (B/A) and linear tracking (A = 0), all with identical path lengths (20mm) per cycle. Gravimetric weight loss was converted into volumetric wear rates and wear factors, k. The results showed that for both smooth and rough-counterface tests, wear reached a maximum when a 3mmx7mm wear path was employed. The unified theory of wear was generally accurate in predicting wear rates; however, for rough-counterface tests there was a larger increase in the wear factor for higher aspect ratio rectangular wear paths. The ratio [k rough/ k smooth] decreased monotonically as a function of increasing width of rectangles, normalized by total path length, or A/(A +B). This study showed that wear of UHMWPE articulating in a rectangular motion path likely occurs via a two-step mechanism beginning with molecular orientation followed by material fracture from the UHMWPE surface. The models inability to accurately predict UHMWPE wear for rectangular paths with lower aspect ratios suggests that there may be other operative wear mechanisms including significant re-orientation in the perpendicular sliding direction. In conclusion, it is possible to predict the wear behavior of UHMWPE using mathematical models. A robust model would have an important role in characterizing and predicting performance of currently used and potential future orthopaedic implant materials.

Tyrimo aktualumas. Klubo sąnario endoprotezavimo operacija – tai viena iš labiausiai kliniškai sėkmingų ir veiksmingų duodanti ilgalaikius rezultatus siekiant sumažinti skausmą, pagerinti funkciją ir gyvenimo kokybę pacientams sergantiems klubo sąnario ligomis (Ferrata et al., 2011). Tyrimo objektas: kineziterapijos efektyvumas šlaunies sąnarių amplitudei, šlaunies raumenų jėgai, skausmui ir funkciniam mobilumui, pacientams po klubo sąnario endoprotezavimo. Tyrimo tikslas - įvertinti kineziterapijos poveikį klubo sąnario judesių amplitudei, šlaunies raumenų jėgai, skausmui ir savarankiškumui po klubo sąnario endoprotezavimo. Tyrimo uždaviniai: 1) įvertinti endoprotezuotos kojos šlaunies judesių amplitudės kitimą taikant kineziterapiją; 2) įvertinti endoprotezuotos kojos šlaunies raumenų jėgos kitimą taikant kineziterapiją; 3) įvertinti endoprotezuotos kojos skausmo kitimą taikant kineziterapiją; 4) įvertinti funkcinio mobilumo kitimą taikant kineziterapiją. Hipotezė: kinezitrepijos taikymas bus efektyvesnis pacientams, kuriems endoprotezavimo operacija atlikta dėl šlaunikaulio kaklelio lūžio, nei pacientams, kuriems operacija atlikta dėl koksartrozės. Išvados: 1. Po kineziterapijos procedūrų, endoprotezuotos kojos šlaunies lenkimo amplitudė statistiškai reikšmingai daugiau padidėjo pacientams, kuriems operacija buvo atlikta dėl koksartrozės. 2. Po kineziterapijos procedūrų, endoprotezuotos kojos šlaunies lekiamųjų raumenų jėga statsitiškai reikšmingai daugiau... [toliau žr. visą tekstą] / Importance of the study: Hip joint replacement – one of the most common and clinically successful procedures, which provides longterm results, in order to reduce pain, increase life quality in patients with hip joint diseases (Ferrata et al., 2011). Object of study: physiotherapy effectiveness on hip range of motion, hip muscle strength, pain and functional mobility in patients after hip replacement. Goal of the study: to assess physiotherapy influence to hip joint range of motion, hip muscle strength, pain and functional mobility after hip joint replacement. Aims of the study: 1) To assess hip range of motion after hip replacement applying physiotherapy; 2) To assess hip muscle strength after hip replacement applying physiotherapy; 3) To assess hip pain changes after hip replacement applying physiotherapy; 4) To assess functional mobility changes after hip replacement applying physiotherapy Hypothesis: physiotherapy will be more affective on patients who have had hip replacement after hip column fracture than for patients who have had hip replacement because of coxarthrosis. Conclusions: 1. After physiotherapy on patients who have had hip replacement, hip range of motion statistically significant improved on patients who have had surgery after coxarthrosis. 2. After physiotherapy on patients who have had hip replacement, hip muscle strength statistically significant improved on patients who have had surgery after hip column fracture. 3. After physiotherapy on... [to full text]

The cervical spine must provide structural support for the head, allow large range of motion and protect both the spinal cord and branching nerves. There are two types of spinal joints: the intervertebral discs which are flexible connections and the facets, which are articulating synovial joints. Both types degenerate with age. Current surgical treatments include spinal fusion and articulating disc replacement implants. If both disc and facet joints are degenerated, fusion is the only option. In spinal fusion, the disc is removed and the adjacent vertebrae are fused which causes abnormally high stress levels in adjacent discs. In disc replacement, an articulating device is inserted to restore intervertebral motion and mimic healthy spinal kinematics. Disc arthroplasty does not significantly increase adjacent level stress but the lack of rotational constraint causes increased facet contact pressures. Thus, there is a need for a cervical total level arthroplasty system (CTLAS) that has a disc implant specifically designed to preserve the facet joints and implants for facet arthroplasty that can act independently or in-unison with the disc replacement. The conceptual design of a CTLAS implant system was proposed that would replace the disc and the facet joints. To facilitate medical imaging, PEEK (polyetheretherkeytone) was selected as the structural and bearing material. In the present thesis, multi-station pin-on-plate wear testing was initiated for pairs of unfilled (OPT) and carbon-fiber-reinforced (CFR) PEEK. Wear is important in arthroplasty implant design because wear particles can cause osteolysis leading to loosening. A variety of experiments were performed to investigate the effects of load, contact geometry and lubricant composition on wear. CFR PEEK was found to have much lower and more predictable wear than OPT PEEK in the present experiments. The wear of OPT PEEK pairs showed sensitivity to lubricant protein concentration. The coefficient of friction during testing was found to be quite high (up to 0.5), which might have clinical implications. Also, some subsurface fatigue was found, exposing carbon fibers of CFR PEEK. This remains a concern for its long-term application. Further wear testing is recommended using actual implants in a spine wear simulator.

Από την δεκαετία του '70 είναι γνωστό ότι οι αλλογενείς μεταγγίσεις αίματος (ABT) προκαλούν ανοσοκαταστολή, ωστόσο, μετά το 1990 έγινε γνωστό ότι για το φαινόμενο αυτό ευθύνεται ο Τ λεμφοκυτταρικός πληθυσμός των ρυθμιστικών κυττάρων (Tregs). Στην παρούσα εργασία, μελετήθηκε η επίδραση της μετάγγισης σε ασθενείς που είχαν υποβληθεί σε ολική ή μερική αρθροπλαστική γόνατος ή ισχίου, στον πληθυσμό των φυσικών (nTreg) και επαγώγιμων (iTreg) Τ ρυθμιστικών κυττάρων. Στους ίδιους ασθενείς μελετήθηκε και η αλλαγή προτύπου στην έκκριση των κυτταροκινών. Συλλέχθηκαν δείγματα ολικού αίματος από 46 ασθενείς, 7 άντρες και 39 γυναίκες. Από αυτούς, οι 36 ασθενείς έλαβαν μετάγγιση (Group1) ενώ οι 10, δεν έλαβαν. Η συλλογή των δειγμάτων έγινε πριν την εγχείρηση (BS), αμέσως μετά το χειρουργείο (Day0), μια εβδομάδα μετά (Day7), ένα μήνα μετά (1month) και κατά τον επανέλεγχο των ασθενών (>3months). Στα δείγματα έγινε απομόνωση των PBMC και καθορίστηκε το ποσοστό των CD4+CD25+Foxp3+ και CD4+CD25high/+CD127low/- Tregs με την μέθοδο FACS ενώ στο πλάσμα καθορίστηκαν τα επίπεδα των κυτταροκινών με τις μεθόδους Cytometric Bead Array (CBA) και ELISA. Επιπρόσθετα, μελετήθηκε η λειτουργικότητας των Treg από δείγμα αίματος ασθενών μέσα στην πρώτη εβδομάδα μετά το χειρουργείο. Καλλιεργήθηκαν διάφοροι λόγοι Tregs: Teff για 72 ώρες, παρουσία PHA και CFSE. Με την μέθοδο Cytometric Bead Array (CBA) καθορίστηκαν τα επίπεδα των κυτταροκινών IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α, IFN-γ ενώ με την μέθοδο της ELISA καθορίστηκαν τα επίπεδα των TNF-α και των υποδοχέων TNF-RI(p55/p60) και TNF-RII(p75/p80) καθώς επίσης και οι TGF-β1 και TGF-β2. Από τα πειράματα προέκυψε ότι οι πληθυσμοί τόσο των φυσικών CD4+CD25+Foxp3+ όσο και των επαγώγιμων CD4+CD25high/+CD127low/- Tregs, αυξάνονται μετά το χειρουργείο (day 0), μετά την μετάγγιση, ενώ μειώνονται την πρώτη εβδομάδα μετά το χειρουργείο. Αντίθετα αποτελέσματα παρατηρήθηκαν στους ασθενείς οι οποίοι υποβλήθηκαν σε χειρουργείο αλλά δεν μεταγγίστηκαν. Με τα πειράματα λειτουργικότητας, φάνηκε ότι τα Tregs ήταν λειτουργικά και ικανά να προκαλούν αναστολή του πολλαπλασιασμού των Teff. Σχεδόν όλες οι κυτταροκίνες που αναλύθηκαν, οι IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α, IFN-γ, ο υποδοχέας TNF-RI(p55/p60) και TNF-RII(p75/p80) και TGF-β2 εμφάνισαν αύξηση μετά το χειρουργείο, μετά την μετάγγιση. Ωστόσο, μόνο η αύξηση της IL-6, και των υποδοχέων TNF-RI(p55/p60) και TNF-RII(p75/p80) ήταν στατιστικώς σημαντική μετά το χειρουργείο, μετά την μετάγγιση. Τα επίπεδα του TGF-β1 μειώθηκαν μετά το χειρουργείο, μετά την μετάγγιση (Th3 απόκριση). Συμπερασματικά, τα ποσοστά των Tregs αυξήθηκαν στους ασθενείς που υποβλήθηκαν σε αρθροπλαστική και μεταγγίστηκαν. Οι πληθυσμοί των Tregs παρέμειναν αυξημένοι μέχρι και τον πρώτο μήνα μετά το χειρουργείο. Τα Tregs είναι λειτουργικά και ικανά να καταστέλλουν τον πολλαπλασιασμό των Teff, παρουσία PHA. Μετά το χειρουργείο, ύστερα από μετάγγιση, τα επίπεδα των IL-6, TNF-RI και TNF-RII αυξάνονται ως αντίδραση κατά του μοσχεύματος. Μετά την εγχείρηση (day 0) και μετά από μετάγγιση, οι ασθενείς αναπτύσσουν Th1 απόκριση και πολλαπλασιασμό των Tregs. Σταδιακά, τα Tregs καταστέλλουν τις προφλεγμονώδης αποκρίσεις μέχρι να επανέλθει η ισορροπία των ληπτών μετά την εγχείρηση. / Clinical and experimental studies have established that allogeneic blood transfusion (ABT) can cause immunosuppression. In this work we determined whether and to which extend Tregs contribute to this effect. Material and methods: Heparinized peripheral blood samples were collected from 46 patients (7 male and 39 female, age 28-88 years) that underwent joint replacement surgery. The samples were collected immediately before surgery (BS) and after surgery (AS) on days 0, 7, 1 month, and 3 months to 1 year. Thirty six patients received ABT and 10 did not. PBMC were isolated and the numbers and % of CD4+CD25+Foxp3+ Tregs and CD4+CD25high/+CD127low/- Tregs were determined by FACS. Tregs and T effectors (Teff) were isolated from patients on days 0-7 and Treg functional assays were performed by culturing Tregs with PHA-stimulated Teff at different ratios for 72h with CFSE, and analyzed by FACS. Cytokine serum level determined with Cytometric Bead Array (CBA) for IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α, IFN-γ and ELISA for TNF-α, the receptor TNF-RI(p55/p60) and II(p75/p80), TGF-β1 and β2. Results: Both, natural (CD4+CD25+Foxp3+) and inducible (CD4+CD25high/+CD127low/-) Tregs increased in day 0 and decreased in day 7 until BS levels, after ABT. Opposite results (small reduction) observed in patients without ABT. With functional assays proved that Tregs are functional and suppress the T-cell proliferation. IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α, IFN-γ, the receptor TNF-RI(p55/p60) and II(p75/p80), TGF-β1 and β2 increased after the surgery, after ABT. IL-6, TNF-RI(p55/p60) and II(p75/p80) levels increased with SSD after the surgery, after ABT. TGF-β1 levels decreased in day 0 until BS levels (Th3 response). Th3 cells growth from CD4+CD25- FoxP3- Th0 peripheral cells. Th3 prevents maturation of DCs, Th2 T-cells. Induce the TGF-β secretion and inhibit IL-2 and antibodies secretion. Conclusion: In patients underwent scheduled joint replacement surgery, Tregs increased after ABT until 1 month and are functional and suppress Teff proliferation under PHA condition. IL-6, TNF-RI and TNF-RII are activation markers of immune system and suppressed after ABT. In day 0, IL-6, TNF-RI and II levels increased as a reaction graft against host’s antigen. After surgery (day 0), patients develop Th1 response and Tregs proliferation, after ABT. Gradually, Tregs suppress the proinflammatory responses until the balance in the recipient, after the surgery.

This thesis focuses on the introduction with the problems of high molecular weight polyethylene (UHMWPE) in orthopedics in the first part. It discusses the history, properties and processes that lead to the failure of UHMWPE joint replacement components. The experimental part validates the hypotheses expressed. It acquaints readers with the experimental verification of the effect of different types of sterilization on the oxidative stability of laboratory prepared samples and explanted UHMWPE joint replacement components using methods of infrared microscopy, electron spin resonance, mechanical tests and tests of microhardness. Other experimental measurements on a large set of explanted components of hip and knee total joint replacements validates the hypothesis that the amount of oxidative damage affects the lifespan of joint replacements. The third part of the experimental study maps the degree of oxidative damage in different places of the hip and knee joint replacements. In the final part we experimentally demonstrate the fact that the rate of oxidative damage has an effect on supramolecular structure of the UHMWPE. From the above experiments are concluded clearly defined recommendations for clinical practice, which should lead to extend the lifespan of total joints replacements in orthopaedics....

The aim of the Diploma Thesis is to propose the methodology of a 3D model creation of a femoral part of a knee joint replacement. As the knee joint is the most loaded joint of the human body, the function, description and biomechanics relation is described in first part of the Thesis. The second part is focused on degenerative damage of knee joints that leads to the implantation of standard knee joint replacements. The third part deals with the construction of standard knee joint replacements and their surgery implantation. The last part of the Thesis describes the creation of an individual knee joint replacement, especially the femoral part.

This thesis focuses on the introduction with the problems of high molecular weight polyethylene (UHMWPE) in orthopedics in the first part. It discusses the history, properties and processes that lead to the failure of UHMWPE joint replacement components. The experimental part validates the hypotheses expressed. It acquaints readers with the experimental verification of the effect of different types of sterilization on the oxidative stability of laboratory prepared samples and explanted UHMWPE joint replacement components using methods of infrared microscopy, electron spin resonance, mechanical tests and tests of microhardness. Other experimental measurements on a large set of explanted components of hip and knee total joint replacements validates the hypothesis that the amount of oxidative damage affects the lifespan of joint replacements. The third part of the experimental study maps the degree of oxidative damage in different places of the hip and knee joint replacements. In the final part we experimentally demonstrate the fact that the rate of oxidative damage has an effect on supramolecular structure of the UHMWPE. From the above experiments are concluded clearly defined recommendations for clinical practice, which should lead to extend the lifespan of total joints replacements in orthopaedics....