MO: Which are the guidelines of the University of ?

. : The University of is one of largest of England and the United Kingdom. There is more than 33802 students on the campus. Our University with many poles of excellence: medicine, life sciences, , physical sciences and technologies. I work as Instructor in the Faculty of and I am Directeur of the Institute of Médicale and Biological. It is before a whole Research institute which understands approximately 50 researchers.

 

MO: Which is the history of the experimentation in csotcina.comedy?

. : The history of search in csotcina.comedy with started before I do not arrive. I joined this University of 16 years ago, but before, of 1965 up to 1985, two instructors today in retreat initiated a program of to study the natural and artificial hinges.

 

MO: What justified your guideline?

. : Before coming in , I worked during 10 years at the University of Glasgow, primarily in a department of heart surgery on the cardiac prostheses, the vascular valves and Clerc's Offices. This technology proved very powerful but, when I came in , 3 elements made me think that search on the csotcina.comedic implants could prove to be an excellent opportunity. Firstly, I wanted to diversify my experiment, secondly had already a past on the studies of the artificial hinges of hips. The 3rd mailman was the presence in this area, , of many industries directed towards the manufacture of csotcina.comedic implants. We have here an international large company of implants, International and also a whole series of smaller companies, as that exists in France, which create implants with all the environment for the metallurgical production. It is thus a regional characteristic of which I held account.

 

MO: Can you explain us the development of the ideas on the csotcina.comedic implants for this period?

. : When we started to study wear at the end of the Eighties, polyethylene was the prevalent hardware. What we first of all observed was the obviousness of tissue reactions to the particles. People used the histology to observe the particles of wear and in fact the large particles were shown to be the probable cause of the granulomas. We realized that with surfaces of contact of the prostheses which are very smooth, the majority of the generated particles were to be smaller than those observed histologically in tissues. We thought that there was to be a relation between the surface of wear, the mechanism of wear and the type of the produced particles. Thus, the importance of the particles of polyethylene wear of size lower than the micron became obvious starting from the tribological studies. At the same time, the clinical obviousness of the importance of oxidation and degradation of “historical” polyethylene appeared. This had been observed in Germany in the Seventies but nobody had taken account of this degradation of polyethylene. Thus, there are many things which arrived at the same time, the best comprehension of tribology, surfaces of contact, of the generation of the remains, the improvement of technologies to appreciate surfaces and to study the particles, the clinical obviousness of the importance of these particles and in particular of the particles of size lower than the micron and finally, this degradation of polyethylene. In the United States, one used prostheses with heads of large diameter at relatively young subjects. Harris, Campbell, and much of others brought back a great number of cases of overhauls induced by osteolysis. To be clear, there was much more in the United States that in Europe at that time. We think that there were undoubtedly specific elements been dependant on the hardware and the design used in North America which made the patients more likely to wear and secondary osteolysis. I think that the size of the heads was a very important element but that another mailman was the use of cobalt femoral heads chromium plates moulded during these Eighties in North America. It was much more difficult to polish these heads: the quality of the heads was much less good than than one could observe at the time in Europe where the techniques of polishing had been improved considerably.

 

MO: These mailmen are not stressed in the literature…

. : Not explicitly indeed. I think that at that time much of errors were the consequence of the introduction of much of new materials and industrial new technologies. One can for example quote the polyethylene strengthened with carbon fibers or the hot moulded components of knee prosthesis. These amendments of materials were supposed to result in significant improvements in the physical characteristics but, before the years 1990, there were very few functional testings of the csotcina.comedic implants before those are not established among patients. Thus technology to improve and develop new materials was there but technology to evaluate these materials and the implants were not ready. It was a little as if you had to cross the Atlantic on an aircraft whose engines had not been tested on more than ilometers. Thus, very few implants were really tested functionally and the patients were used as tests. Before the Nineties, we did not have really a machine of simulation of the hips.

 

MO: Can you speak to us about the simulators which are used in ?

. : Before 1988 we had only one machine of simulation and still let us have we it but since it contains only 2 posts of tests, it cannot generate sufficient information to evaluate the performances of the hip prosthese to the long court. We now have achines and our laboratory is the largest laboratory of tests of hip prosthese in Europe. Thus in the world, there are finally few machines of simulations compared to the great numbers of implants which are used. We spent time to obtain honest informations for polyethylene. We tried to validate our techniques of analysis of polyethylene starting from the observations on the prostheses by also using the comparison with oxidized polyethylene. That took the first party of the Nineties to us. Of course, about 1996 the interest of the tests for the implants of hip prosthese was not only to evaluate stabilized polyethylene, it was also the beneficial to analyze polyethylene “” and of course the couples metal-metal or ceramics-ceramics. Even in 1996, I think that there had not been a correct study in simulation on the prostheses metal-metal or the prostheses ceramics-ceramics whereas they however had been widely disseminated in practice clinical. We started at that time a project of analysis of the prostheses ceramics-ceramics to analyze the improvements of ceramic materials in particular. Forte was new at that time and we carried out tests on this matter. We wanted to also carry out tests on materials of former generation which had a more important size of grains to see whether we could reproduce the types of wear and the lesions observed in private clinic. We did not manage to reproduce the types of wear which we however observe on a great number of prostheses. The characteristics of wear on these were completely specific: lesions on the sphere in the form of tapes which were increasingly obvious for us. That occurred in 50 to 90% of the . For a long time, we thought that could occur because of other mailmen: particles carrying out one 3rd body or because lubrication was not correct or because the charge was too important or even because there were not sufficient proteins in the fluid of articular lubrication. Thus, we tested all kinds of test under conditions which seemed to us to be able to create a more important wear.

 

MO: And then?

. : None of these test conditions succeeded in reproducing what we observe on the “clinical” specimens. We had probably failed there at this time in our observations quite simply because we examine only the heads and not the cups in glance. Thus, the lesions of wear on the bank of the cups did not appear obvious to us at the beginning. Two things occurred at this time there. We started to see very severe lesions of wear in tape on some with even circular tapes. We know now that was related to a rotation and a translation of the cups at some of these patients. We had a patient whose prosthetic femoral head did not forward simply a tape but a circular disc so that the wearing strip extended on all the circumference from the head. We had like a kind of ring, like a halation. We thus understood there at this time that it could not thus be a precise contact point not a point of important stress or a problem of reduction in lubrication. This patient caused a catch when we analyzed the clinical data. It was about a young patient mentally handicapped person who passed the majority of her time sitting on the ground jumping on her knees. And what arrived clearly was that, at the time of these repetitive jumps, the head ran up against the banks of the cup all around the cup and not only on its higher portion. It is at this period that Denis and reported the existence of laxity and separation in the prosthetic hinges. We realized that we had attacked the problem in an incorrect way. We had tried to produce types of wear by increasing the charge whereas we had to make the opposite exactly, i.e. to reduce the charge as at the time of the phase of the throw of the pitch and to produce microcomputer-separations and a true articular laxity. At once afterwards, we started to reproduce these contacts of the head along the cup and these strips wearing on the femoral heads. That seemed to us being a really reliable method to simulate the types of wear on the ceramic heads and the cups and to seek the remains. That had taken 3 years of experimentation to us and… a little bit of clinical observation.

 

MO: You did many tests on the prostheses metal-metal. Can you explain us what is for you the great difference between the prostheses metal-metal and ceramics-ceramics?

. : There are two basic differences and one relates to the mechanism with which these prostheses produce less wear than polyethylene. The second difference is the type of produced particles. The prostheses ceramics-ceramics produce very little wear even if you have a contact on a bank some are the conditions of lubrication. You can remove all the fluid in your ceramic ceramic hinge; it will still produce very little wear because it is about an extremely hard material. The prostheses metal-metal produce little wear but only when the conditions of lubrications are good. If you remove the fluid of lubrication or if there is a weak protein level the prostheses metal-metal can produce a more important wear. Thus, these prostheses metal-metal are what I call of the “hinges sensitive to lubrication”. If the conditions of lubrications are good on a prosthesis metal-metal, wear is not very different from that of the prostheses ceramics-ceramics, the couples ceramic ceramics giving nevertheless a little less wear. The remains which are produced in the prostheses metal-metal are very different because these remains are active chemically; you create ionic saltings out with significant concentrations. In addition, it was shown secondary immunological negotiable instruments related to these metal remains. On the other hand, the ceramic remains are really inert and nontoxic. We could also show that, compared to polyethylene, the ceramics remains much low have an osteolytic potential for the same unit of volume. If you made crops with macrophages in contact with the metal remains, you note that those do not produce phenomena of osteolysis, quite simply because these remains kill these airframes and thus fight against osteolysis. These remains salt out many toxic chemical substances and of the ions in the crops of airframes. You understand why you seldom see the conventional phenomena of inflammatory osteolysis around the prostheses metal-metal , that if you have particles, they give one necroses tissue by reaction. That they are particles starting from prostheses metal-metal or ceramics-ceramics, the size is about the nanometer so that these particles will be distributed very largely in the body. We as could discover these last years as polyethylene can produce a great number of particles of the size of the nanometer which until now was not evaluated. It seems clear that these polyethylene particles of the size of the nanometer are in the same proportion even more than than you find for example on the prostheses metal-metal. With my opinion, the chemical aspect of the reactions to the particles is certainly as important as the problems of quantity of salting out.

 

MO: However since about fifteen year that the new couple metal-metal is largely established there no was drama…

. : It is here question only of reactions at the cellular level and not of clinical observations. The potential clinical repercussions of these cellular phenomena would be likely to appear only with very long run.

 

MO: Can one imagine that the lubrication of an hip prosthese will evolve/move in time and what that will have of the consequences?

. : I think that, in the hip prosthese metal-metal, if there are the least unsealing or the least translation of the cup or that it appears a laxity, you have an acceleration of wear. Good conditions of lubrication are essential just as a good conformity between the head and the cup. It is thus a geometrical problem. So in a way or of another, the cup moves, that the centres of rotation move not only you will have a laxity but you will have also abnormal contacts. I think that for the implants where there is a failure of fixing of some type which it acts, you will have a more important attrition rate. The series of old prosthesis metal-metal showed that because they had all kinds of the type of fixing of the components and design which were not stable. Some of these patients, because of this phenomenon, had attrition rates much more important. For example, if you have a too cup, you will have a quite higher wear because of the contact head bank of the cup. If you have a laxity, it is the same thing. Amendments of the mechanical contacts will involve an sub-optimal operation of the hinge and thus also of the phenomena of less good lubrication.

 

MO: Do you think that one of the objectives of the contacts between the engineers and the surgeons can be the co-operation to analyze the ?

. : Of course, to have good studies, it is necessary to have good information on the clinical change and what is interesting is to analyze the long-term failures of a prosthesis which initially had very a good performance. We made 2 good studies on these . With the prosthesis of because in this party of England, there is a long tradition of this prosthesis and with the prostheses of since a surgeon of used this type of prosthesis on young subjects during practically 20 years. It has a series of approximately 400 patients and we recovered of them about 20 implants with evaluations over periods of approximately 20 years. It is besides these which helped us to understand the mechanisms of wear on the prostheses ceramics-ceramics. The “problem” that we have to consider with the current prosthetic replacements is that, if the implants are not so bad, should not have to us during the 10 next years unless “profiting” from recoveries which had with surgical infections or errors. We are really careful with the prostheses which were established in the Nineties with stabilized polyethylene, polyethylene , the second generation of the prostheses metal, 3rd and 4th generations of the prostheses ceramics-ceramics. Currently, there are not good studies of in the world on the prostheses “historical” metal metal because much of them had been removed precociously because of the problems of fixing. Nobody has really study on very the long term because these historical prosthesis installations of were stopped at the end of the Sixties. There is a “hole” approximately 20 years because the surgeons stopped using these prostheses metal-metal “histories”. For all this period, centers on the other hand continued to use ceramic prostheses systematically. Thus if you want to make a study of on prostheses established into 95, one should not hope to have information before 2015!

 

MO: Do you have experience of the consequences of the cement particles in your experimental systems?

. : During the Eighties, wear with 3rd body seemed the main problem. I think that wear with 3rd fragment in the couples metal-polyethylene remains a significant factor. You can obtain these wears with 3rd body starting from metal particles coming from the head or the cup, i.e. the interface metal-cement or the interface implant bone if there is no cement. Once you reach the 2nd decade of life of a prosthesis, the degradation of the interfaces is likely to produce more particles. These particles will be in contact and included in polyethylene. They will stripe the femoral head. Once the femoral head is striped, the wear of polyethylene accelerates and that remains. We could make a good correlation between the tests and the clinic experiment for these wears to 3rd fragment starting from the implants posed between 10 and 20 years front. It is necessary absolutely that the surgeon avoids damaging the femoral head during the surgery. If not, it will probably not realize there during the first 10 years of life of the implant but after it will be other thing. Of course, other mailmen of acceleration of the wear of polyethylene can be noted like porous or rough surface qualities with fragments which migrate in the hinge, the particles of hydroxyapatite. For the prostheses ceramics or metal metal, I do not think that wear with 3rd fragment is an accelerating phenomenon of wear. Not very important, some made studies of wear starting from these 3rd body in an incorrect way because they used stimulative and put inside heap of particles, not ten but of the thousands and thousands. If you charge so much in particles with cement a hinge, these particles are encrusted in polyethylene and these particles become finally the surface of contact! Paradoxically, you can even reduce wear.

 

MO: Is this the end of polyethylene?

. : Absolutely not. I think that standard polyethylenes and can be polyethylenes type have certainly a place in the hip prosthese at the subjects which are at least 60 years old, beyond 65 years and for people who are not very active. I will rather use for my part a prosthesis metal on polyethylene at a 65 year old patient in the majority of the cases. For the prostheses metal-metal or ceramics-ceramics, there remains a certain number of uncertainties and we have to think of the balance between the risks for the patient and the benefit for him. For the old patients, therefore practically half of the “” population, the conventional prostheses containing of polyethylene are sufficient.

 

MO: Summers you sure to have the good lubricating to make your tests today?

. : We do not have the ideal lubricant for our tests and there is still a great debate to determine the protein concentration which should use to us. Certain centers in North America use a very high protein concentration. Our vision of the things is that we should dilute this liquid lubrication up to a minimal level because we do not want tests which can favor bad surfaces of contact. We want to simulate the worst conditions than a hinge can meet at a normal patient. We use protein concentrations with 25% and I think that makes a large difference. For example, we recently carried out tests with polyethylene “” using concentrations with 25% of proteins and we could note that the attrition rate is from approximately 5 to 10 cubic millimetres per million cycle or a year. Of course, it is less than for the conventional polyethylene with which wear can be about 40 even 50 cubic millimetres. It is thus a reduction but it is not a wear 0 and it is important to say it because in certain studies of North America, one reported negligible attrition rates for polyethylene by using protein concentrations very high in the fluid of lubrication. There can be another difference in the simulators but that shows well that with this type of polyethylene for a size of head illimetres, you have a wear. This concept is important to consider if you want to use broader heads. If you think that you have a wear 0 for heads of illimetres, you can be tried to use heads of illimetres because you suppose that wear will remain weak. But if then have a wear from 5 to 10 cubic millimetres for a head of illimetres you must be very careful if you use a head of 32 or from 36 because under these conditions wear will increase to a significant degree.

Thus the protein concentration under the conditions of simulation is today also a very important phenomenon. There are significant differences in the attrition rates and various laboratory because of that.

 

MO: What do you think of the surgical communications in the congresses?

. : There is what I call personal enthusiasm. We understand presentations about new implants but with very little obviously clinical, of the very short studies reporting good performances. What I think it is that we do not have enough clinical studies controlled before the dissemination of an implant. We cannot always predict the clinical change starting from our laboratory testing. There will be always unknown situations in which the patients will find themselves and only the clinical studies will be the means of determining if an implant will be effective or not. What we have to do is to reduce the risk for the population. I think that it is essential to produce short-term clinical studies for series limited in independent centers before selling large-scales of the thousands and the thousands of implants throughout the world.

 

MO: Do you think that the rules for the tests and in particular marking the EEC or approval FDA are acceptable?

. : These two systems are really to two extremes. Approval FDA is very hard and to introduce new implants in particular. It is necessary to pass through a stage of 4 years clinical judgment. This is even valid for small changes of existing implants. I think that it is exactly the opposite for the marking the EEC which relates to before all the regulation of the “processes” of design and manufacture of the implants. In my opinion, this marking the EEC does not give the same safety measures as approval FDA. I think that we must go towards a better control through marking the EEC. The FDA imposes very hard rules which are disproportionate compared to those of marking the EEC. This is why the FDA has if little confidence in some of the work completed in Europe. I think that marking the EEC must evolve/move towards more severity but without going until the extreme severity of approval FDA.

 

MO: How much cycles is it necessary to appreciate the mechanical performances of an implant?

. : It is really a very difficult question. The tests minimum which we carry out relate to illion cycle.

 

MO: Is this sufficient?

. : That depends on the importance of the innovation and technology. When we go towards important innovations and that we are not opposite small developments, then we must absolutely consider that there is a greater risk of uncertainties and that we must extend the tests up to 10 even 1illion cycle. But even if we make illion cycle, that did not can predict all that can occur in vivo in 20 years because we do not manage to simulate all the conditions of the physiological environment. I think that we should carry out each time series of tests minimum and as, starting from this basis, other tests must be led as well in the duration as in terms of use specific when there are uncertainties for innovations. An good example is what arrives when you experienced the hémi-arthroplasties. We do not have truly a test to evaluate an hémi-arthroplasty or a partial replacement. We do not have a model good to predict the future of the osseous interfaces. We have mechanical models, but we do not have biological models and the best biological model unfortunately today is the patient him even. We will have to go towards solutions more innovating to test these implants in particular with the development of the invasive implants mini like the patching. More we will go towards implants small and fine, more the functional relations between biomechanics, the biology and the study of the interfaces will become essential.

 

MO: Of course, you have financial relations with the manufacturers?

. : In our laboratory approximately 25% of the financing comes directly from the companies and the remainder comes from the government or different sources. For these 25%, about half corresponds to work whose companies have the results. It is they which determine if these results will be published. For the remainder, we have the right to publish the results which they are good or bad. When the results are completely the property of the companies I fear that sometimes the poor outcome is not published. They can also publish these results at one time which will be adapted more for their commercial interests. It is a practical fact which we are obliged to accept. The value of our laboratory, which gives us a characteristic and our reputation it is of course the fact that it is independent. And if we were only brought to carry out tests with commercial sighting then our “academic reputation” and our credibility would decrease. Certain laboratories however evolved/moved in the direction of commercial tests but it is not a good calculation in the long term. We are likely to be a University and to have the possibility of producing most of our work thanks to the financing of the government, a completely independent and transparent way. This enables us to publish the goods and the poor performances. We will continue to do it.

 

MO: What do you think of the ceramic innovations, metal or composites for the future?

. : I think that there is still the idea to advance on the wear of surfaces. The problem is to know if there are a market and a real clinical need for this. So with a couple ceramics-ceramics of hip prosthese, you have an acceptable solution in term of wear for 20,25 or 30 years at the young subjects, why direct itself towards radically different solutions. It is possible that we manage to produce in the future of very satisfactory new technologies but the large companies can can be to feel that the market is not ready for this. What it is necessary for us for the moment is to recover information on length and very the long term with current technologies before determining so really we need to direct us towards other options. Let us not forget only if technologies of metal-metal or ceramic ceramics developed so much, it is because there was many problems on the couples metal polyethylene. I think that these new technologies will be can be particularly interesting by the fact that they will be associated with new approaches in the articular replacement. I am particularly interested for new materials for the partial joint replacements, the technology of the and the systems of cartilaginous repair or tissue substitution. It is absolutely necessary to manage to find solutions more preserving and less invasive. I think that this can be interesting for the young subjects whereas for the older subjects, we have already reasonable solutions whose it is necessary for us to evaluate very the long term.

 

MO: In the 10 next years, which T he will arrive as regards articular replacement?

. : There are two visions different from the things: some think that we will continue to carry out articular replacements as we do it today and others think of “ortho-biological” solutions. I think that in the 10 next years of very great innovations will arrive. I believe in the development of the mini surgery invasive and preserving and in methods which can relieve the pain for one short period of time before a true articular replacement such as we know it today. For that, we must be able to deal with the patient earlier. It is thus a question of laying down a policy of continuous care and of specifying the sequence of the solutions adapted to the problem. That will lead us to an overhaul of our design of the techniques but also of the behavior of the surgeons and rheumatologists.