Coating processes – Medical or dental purpose product; parts; subcombinations;... – Implantable permanent prosthesis
Reexamination Certificate
2002-08-05
2004-02-17
Beck, Shrive P. (Department: 1762)
Coating processes
Medical or dental purpose product; parts; subcombinations;...
Implantable permanent prosthesis
C427S002100, C427S002240, C427S002270, C427S243000, C427S270000, C427S283000, C427S336000, C427S338000, C427S403000, C427S414000, C427S430100
Reexamination Certificate
active
06692790
ABSTRACT:
The invention relates to the field of medical implants. More in particular, the invention relates to a coating which improved the biocompatibility and bone-bonding properties of medical implants, such as orthopedic and dental prostheses.
Recently, a biomimetic coating has been developed for coating medical implants with ceramic materials, such as bone-like hydroxyapatite. This technology has been disclosed in European patent application 98203085.0 and comprises soaking an implant material, e.g. a scaffold for tissue engineering bone, into a super saturated calcium phosphate solution resembling a physiological fluid. A calcium phosphate layer uniformly precipitates on the implant surface under modulated nucleation and crystal growth conditions. This method mimics the way hydroxyapatite bone crystals are formed in the body. Considering the physiological conditions under which the biomimetic coating is grown from a fluid at body temperature, biologically active agents, such as antibiotics, can be coprecipitated.
In EP 0 806 212, an implantable coated device is disclosed that comprises a calcium phosphate layer, in which a biologically active substance may be incorporated. The coating comprising calcium phosphate and a growth factor can give rise to an enhancement of bone formation. For the preparation of the coating the surface of the device needs to have a roughness(Ra value) 10-1,000 nm.
WO 97/41273 describes a process for coating a metallic or ceramic substrate by heating a certain mineral solution, in which the substrate is immersed, to a high temperature until the pH is at least 8, after which deposition of crystalline carbonated hydroxyappetite is on the substrate is induced. Such a coating is reported to be osteoinductive, but the incorporation of bioactive agents is not disclosed. It is unlikely that the process would be suitable for such purpose, since the combination of a high temperature and a high pH, would have a detrimental effect on the thermosensitive bioactive agents.
Many mineralized tissues in living organisms are composed of crystals formed under well-controlled conditions. Proteins are key participants in the control process. Some proteins envelop the individual crystals, whereas others are occluded inside the crystals. How these proteins become occluded inside a crystal and what their role is in the crystallization process and in the determination of the properties of the crystal still remains unclear.
The present invention seeks to find a way of using the expected controlling function of proteins in mineralization processes. In particular, it is an object of the invention to find a way of using a protein to induce mineralization, calcification and/or the formation of bone tissue on a medical implant.
These objects, as well as other objects of the invention that will become clear from the present description, have been achieved by virtue of a proteinaceous coating to the implant which is applied thereto in a specific manner. Accordingly, the invention relates specifically to a method for providing a proteinaceous coating on a medical implant, comprising the steps of:
submersing the implant in a first aqueous solution comprising a protein and magnesium, calcium and phosphate ions through which a gaseous weak acid is passed;
degassing the solution;
allowing a coating to precipitate onto the implant;
submersing the coated implant in a second solution to redissolve the magnesium, calcium and phosphate ions and to obtain the proteinaceous coating.
Surprisingly, it has been found that a proteinaceous coating may be provided on a medical implant, which coating induces nucleation and growth of calcium phosphate crystals, both in vitro and in vivo. Although the coating itself will typically not contain any calcium phosphate material, it has been found to act as a type of template or matrix for mineralization. This advantageous property allows for the application of the medical implant to serve as a scaffold for tissue engineering bone tissue.
On the other hand, said property of course also increases the suitability of the implant for the purpose it originally had, i.e. being implanted in a patient in need of a bone substitute. The proteinaceous coating described herein can induce deposition of a variety of calcium phosphate compounds containing carbonate and others ions on the surface of an implantable device. The layers will be similar in composition and crystallinity with bone and teeth minerals and have desired bioresorbability, bone-bonding properties to improve the biological fixation of medical devices to living calcified tissue.
The proteinaceous coating may further form a composite with calcium phosphate crystals, for instance in vivo, leading to a biomimetic coating with mechanical properties superior to those of conventional ceramic coatings. It is believed that the protein may function as a reinforcement of a biomimetic coating by bonding calcium phosphate crystals together.
Furthermore, the proteinaceous coating enhances attachment of cells and improves the biocompatibility and bone-bonding properties of medical implants.
The medical implant on which a coating is applied in accordance with the invention may be of any inorganic, metallic, polymeric or organic material. The implant may be flat, dense or of a complex shape. It may have a porous, beaded or meshed ingrowth surface.
Metals, such as stainless steel, titanium, nickel, cobalt, chrome, niobium, molybdenum, zirconium, tantalum, and combinations thereof, can be coated for orthopaedic and dental applications. For example, devices used in total hip arthroplasty such as porous or non-porous acetabular cups and the proximal region of hip stems may be coated.
Ceramic materials, such as alumina and zirconia, glasses such as bioactive glasses made of CaO—SiO
2
—P
2
O
5
, and calcium phosphates, such as hydroxyapatite and tricalcium phosphate, may be coated.
The subject coatings can be applied to various polymers and plastics, more preferably biocompatible or bioresorbable ones like polyactive™, a copolymer of polyethylene glycol and polybutylene terephtalate.
Before applying the coating, the substrates are preferably cleaned or treated to remove any surface contaminants and to promote good adhesion of the coating. Various methods for cleaning may be employed. The metallic implants may be rinsed with a degreaser, i.e. acetone, alkyl alcohols, etc. and then thoroughly rinsed with pure water.
In order to improve coating adhesion, various surface treatments may be applied to metal implants. Mechanical surface treatments, such as sand-blasting, scoring, polishing and grinding can increase surface roughness of the implants and improve the bonding strength between the coatings and substrate. For similar purposes, chemical surface treatments may be also applied to metal substrates prior to coating. Among others chemical treatments available for metals, acid etchings will be preferred by treating implantable devices with strong mineral acids, such as hydrofluoric, hydrochloric, sulfuric, nitric and perchloric acids. It may also useful to treat the metal devices with oxiding agents such as nitric acid, peroxyhalogen acids, hydroxyperoxides, or hydrogen peroxide to form a fresh metal oxide layer. After the mechanical or chemical treatment, it is necessary to rinse the implants with pure water under ultrasounds for removal of surface contaminants.
The method for coating medical implants consists of soaking medical implants into a calcifying solution comprising a protein at low temperature. This simple method is based on the finding that calcium phosphates are more soluble in mildly acidic medium than at neutral and even basic pH. This also applies at conditions which essentially do not affect the stability and activity of the protein in a harmful way. Thus, aqueous solutions of calcium and phosphate ions and a protein can be more concentrated at mildly acid than at neutral pH. In other words, calcium phosphates precipitate at neutral or basic pH while they remain soluble at mildly acidic pH from a solution having the
de Groot Klaas
Layrolle Pierre Jean F.
Liu Yuelian
Banner & Witcoff , Ltd.
Beck Shrive P.
Chienna B.V.
Kolb Michener Jennifer
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