Method of bone cement preparation

Agitating – In vacuum chamber

Reexamination Certificate

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C366S163100

Reexamination Certificate

active

06709149

ABSTRACT:

This invention relates to a method of bone cement preparation. It further relates to a bone cement mixture obtained by said method and an apparatus for performing said method.
The invention allows for preparation of a pore-free, mechanically superior bone cement, in a closed system that requires minimal human intervention, and delivers a consistent, operator-independent performance.
Surgical bone cement is commonly used for fixation of joint prosthesis, most frequently in total hip and total knee replacement. It is prepared by mixing a powder component, comprising emulsion polymerized polymethylmethacrylate (PMMA), with a methyl-methacrylate (MMA)-based liquid. The conventional catalytic system for the room temperature curing resins is based on the chemical decomposition of benzoyl peroxide by an accelerator, N,N-dimethyl-p-toluidine. Decomposition of benzoyl peroxide releases free (phenyl) radicals and initiates polymerization of MMA. Benzoyl peroxide is either residual, i.e. left over from the polymerization of the PMMA powder, or is added in powder form to PMMA. The accelerator is added to MMA liquid, which, at the least, also contains radical scavenger hydroquinone to prevent accidental polymerization.
In conventional bone cements, introduced to total hip replacement (THR) surgery by Dr. John Charnley in the early sixties, the powder and the liquid components are mixed together, either by a spatula in a simple bowl, or in dedicated mixing/delivery devices. Increase in the clinical use of dedicated mixing devices has been driven by mostly two factors: (i) hand mixing in open air leads to air bubble inclusions which significantly reduce the strength of bone cement; (ii) undesirable exposure of the operating room personnel to monomer vapours. Pores within the bone cement mantle, caused mostly by inclusion of air bubbles during mixing, reduce its fatigue strength, which is now generally accepted to be a major risk factor in aseptic loosening of cemented prosthetic components.
Mixing of the powder and the liquid aims at full wetting of the powder, i.e. all beads should be surrounded by the liquid. Upon decomposition of benzoyl peroxide and release of free radicals, monomer polymerizes with nucleation on the partially dissolved surface of the beads. The amount of monomer relative to powder is thus determined by predominantly physical, rather than chemical considerations. Three characteristics of polymerization effect the outcome and set the limitations on the possible improvements. Polymerization is:
(i) exothermic:
polymerization of MMA into PMMA releases a fixed amount of heat per mole (55,6 kJ/mol). Release of polymerization heat could increase the temperature of the bone cement mixture by more than 100 deg C, but due to heat transfer into surrounding tissues and the prosthesis, temperatures at the interface to bone rarely exceed 60 deg C. The ratio of monomer to polymer is an important factor influencing final temperature increase. Less monomer to polymerize means less heat released, and the more polymer there is to warm up, the lower the temperature. Bone cement according to this invention uses about 20% less monomer than conventional hand mixing formulations, which results in reduced peak temperatures (by about 8 degrees C).
(ii) density increasing:
density of MMA monomer is 943 kg/m
3
, density of the polymer is 1180 kg/m
3
, i.e. polymerization is associated with volumetric shrinkage of about 20%. With a typical ratio of polymer to monomer of 2,1:1, this leads to an expected cured cement shrinkage of about 6,5%. However, the ultimate, experimentally measurable, volumetric shrinkage depends on other factors, most importantly on the amount of pores within the cement. Presence of pores allows for shrinkage to be compensated from within, i.e. the pores get larger and the volume change measured from outside is less than if the cement were pore-free. In general, all methods deployed to reduce cement porosity lead to an increase in shrinkage. Reduced use of monomer in the cement of this invention is of an advantage here as well; about 1% less shrinkage is expected, other factors (i.e. cement and sample preparation technique) being the same.
(iii) incomplete:
polymerization process depends on formation of free radicals to initiate it, nucleation on the extant polymer surfaces and availability of monomer molecules to extend the growing chains. In all cases, a number of monomer molecules will not find their way into polymer chains and will thus remain as residual monomer within the polymerized matrix. Polymerization process will continue at a very limited rate even after most of the polymer matrix is formed due to mobility of monomer molecules through the polymerized matrix. That same mobility allows monomer to leach out of the cured cement. This is deemed undesirable in view of tissue compatibility. The range of residual monomer found in commercial cements right after preparation is about 2 to 6% (monomer weight per total weight). In time (with quasiequilibrium reached in 2 to 4 weeks) this is reduced to less than 0,5% due to combined effects of continuing polymerization, migration and release of free monomer. Again, reduced use of monomer in the cement of this invention is of an advantage here as well; less monomer to start with leads to a lower residue (about 20% compared to the best selling regular viscosity cement).
In the early eighties the shortcomings of hand mixing and delivery of bone cement became widely acknowledged. With the first long term studies of improved cementing techniques becoming available, showing better clinical results than traditional hand mixing/hand application, the interest for, and clinical use of various systems for bone cement preparation has been steadily increasing. Disappointments with the clinical outcomes of cementless prosthesis have also contributed to re-establishment of cemented total joint replacement as a standard procedure, especially for the femoral component of the total hip replacement and for total knee prosthesis.
All known, commercially available and clinically used mixing systems are designed to remove air inclusions which are invariably introduced at the time when the liquid and powdered components are brought into contact. This task can only be partially accomplished due to mostly time limitations imposed by dissolution of PMMA in MMA and kinetics of polymerization.
Centrifuging:
Championed by Dr. William Harris, Boston, centrifuging was found to be partially effective in reducing the porosity of certain commercial brands of bone cement. While centrifuging could be used with some of the existing cements, it required cumbersome equipment, chilling of cement (to reduce viscosity and prolong setting time) and tight coordination of operating room personnel. It has found rather limited clinical acceptance in the U.S. and even less in Europe. The use of the bottom-up filling technique for the femur by means of a caulking gun, syringe and a long nozzle, as well as pre-plugging of the femoral canal to allow for cement pressurizing have also been introduced by Dr. Harris. Currently, both, the older top-down and the bottom-up filling technique are used in Europe; in the U.S. the latter is dominant.
Partial Vacuum Mixing:
Developed and brought into clinical use by Dr. Lars Lidgren, Lund, this technique was adopted from the dental field where the same materials have been used for decades before introduction into orthopaedics. In molding of dentures from MMA/PMMA resins, air entrapment has also been recognized as undesirable; here less for reduction of strength than for difficulties of hygiene maintenance in dentures with pores which may be open to the surface. Mixing the cement in a bowl under partial vacuum (of some 100 mbar) reduces the porosity of the material cured at atmospheric, or elevated pressure. Partial vacuum mixing systems have found the widest clinical acceptance. Regular viscosity cements, such as Palacos R, are usually chilled (to reduce viscosity and prolong the setting time) for preparation in these systems and for extru

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