AU2000259855A1

AU2000259855A1 - Bioactive calcium phosphate composite layers electrochemically deposited on implants

Info

Publication number: AU2000259855A1
Application number: AU2000259855A
Authority: AU
Inventors: Petra Becker; Hans-Georg Neumann; Peter Zeggel
Original assignee: DOT GmbH
Current assignee: DOT GmbH
Priority date: 2000-07-17
Filing date: 2000-07-17
Publication date: 2002-05-02
Anticipated expiration: 2020-07-17
Also published as: AU2000259855B2; WO2002005862A1; CA2416201A1; HK1060070A1; AU5985500A; CA2416201C; WO2002005862A8; EP1301220A1; JP2004503333A

Description

9 January 2003 DECLARATION I, Johannes Reckzeh, being technical translator and member of Bundesverband der Dolmetscher und Ubersetzer e.V., do hereby declare that I am conversant with the German and English languages, and I certify that the following translation is to the best of my knowledge and belief a true and correct translation of the authentic text of the International Patent Application PCT/EP00/06838 titled ,,Elektrochemisch abgeschiedene, bioaktive Calciumphosphat-Kompositschichten auf Implantaten" ............ .................

WO 02/05862 PCT/EP00/06838 Bioactive calcium phosphate composite layers electrochemically deposited on implants For about 10 years investigations on calcium phosphate layers electrochemically deposited on bone implants have been carrying out with the objective to improve the compound between the bone tissue and implant (Redepenning, J. et at.: Chem. Mater. 2(1990) 625-7; Redepenning, J.G.: US 5 310 464, US 5 413 693; Teller, J. et al.: DE 4 431 862, EP 774 982, US 5 759 376; Kumar, M. et al.: J. Biomed. Mat. Res. 45(1999) 302-10). Calcium phosphates as mineral constituents of the bone tissue have bioactive properties, i.e. they assist the bone formation. The genesis of calcium phosphate layers from electrolytic bathes deposited on implants are very similiar to the processes proceeding during the bone growth. Their microporous structure encourages the immobilization of cells, leading of which new bone tissue is allowed to form and to knit together with the bone tissue surrounding the implant such as with the normal wound healing. In the literature, besides the preparation of phase-pure calcium phosphates it is also informed on composite layers electrochemically deposited on implants. US 5 205 921 (Shirkhanzadeh, M.) and DE 4 431 862 (Teller, J. et al.) describe the electrochemical deposition of calcium phosphate composite layers from tricalcium phosphate and hydroxylapatite therefore from two more difficult soluble calcium phosphate phases. DE 19 504 386 (Scharnweber, D. et al.) deals with an electrochemical method for the preparation of a refined adhesive-proof coating from calcium phosphate and metal oxide phases on titanium implants by a mutual cathodic and anodic 2 polarization. Another method of the preparation of adhesive proof hydroxylapatite/ cobalt composites leads from electrochemically deposited brushite layers which are chemically converted into hydroxylapatite and are subsequently coated with cobalt in another bath (Zhang J.M. et al.: J. Mat. Sci. Lett. 17 (1998) 1077-9). With the difficult soluble calcium phosphate phases, in particular hydroxylapatite, which is striven for with the preparation of these composite layers it is sought to achieve a possibly great likelihood to the structure of the natural full developed bone, and healing the implant into the bone shall be encouraged with that. Then, it can always be assumed that due to its low solubility the hydroxylapatite remains on the implant, and thus a durable improvement of the interaction between the implant surface and biological system will be achieved. Also, any other attempts to completely convert brushite layers electrochemically deposited on implants into hydroxylapatite lead from the objective to artificially develop bone similiar relations on the implant, forever. Although the body thus is offered a surface known to it, such layers have the disadvantage such that due to their low solubility they only excite the bone moderately for the endogenous osteosynthesis. From the literature it is known for several years that the grade of bioactivity of a layer is growing with its instability in a physiological ambiance. Good conditions for the reproduction and differentiation of the osteoblasts responsible for the bone formation are provided by the local increase of the concentration of calcium and phosphate ions in the healing zone of the implant. (Ducheyne, P. et al.: Biomaterials 11(1990) 531-40). Calcium phosphates with a solubility being very much higher than that of brushite and monetite in comparison with hydroxylapatite thus have a particular importance especially for the healing phase of the implant into the bone.

3 Hence, the invention is based on the object to deposit a layer on the bone implant which optimally assists healing the implant into the bone, which then will be entirely resorbed and thus enables the immediate and complete friction-fit contact of the bone with the implant. According to the invention this object is solved by the features of claim 1. Advantageous embodiments result from the subordinate claims. The composite layer according to the invention especially includes the more easily soluble phases of the young bone tissue in addition to the more difficult soluble calcium phosphate phases of the more developed bone. In particular, the easily soluble phases of brushite and monetite are allowed to actively assist the endogenous osteogenesis by locally increased calcium and phosphate concentrations since the reproduction and maturation of osteoblasts required for the osteogenesis is accelerated under these conditions. After the dissolution of the more easily soluble phases has taken place the more difficult soluble phases ensure a slightly increased concentration of calcium and phosphate ions over a longer time period in the healing zone of the implant and thus encouraging the enlargement and stabilization of the new bone tissue. Due to the high-porous structure adjustable by the parameters of the electrochemical deposition, the composite layer is not allowed to serve and shall not serve as a barrier between the implant and bone, but it shall serve such as a harmonizing factor or host with endogenous structuring the boundary layer between the implant and bone. The high bioactivity of this spongy composite is manifesting itself in excellent moistening due to the body fluid present in the wound bed of the bone and the adhesion connected therewith of the factors included in this fluid and stimulating the osteogenesis.

4 The composite layers can be adapted to the respective implant and the bone surrounding the implant with respect to the structure, composition and thickness. The preparation of this composite is allowed then to take place such that the individual phases are simultaneously or subsequently deposited as well, and portions of one phase, e.g. of the more soluble calcium phosphate phase, respectively are converted into a legs soluble phase by means of a chemical reaction. On that occasion, superficially it is not intended to provide a vertical solubility gradient in the composite. The different-phases rather are to laterally develop side by side and dissolve again after implantation. Then, the porosity of the composite first will increase due to the decrease of the more easily soluble phases, and it will be made room for a new bone tissue until the entire composite is also converted into a bone tissue after dissolving the less soluble calcium phosphate phases. Assuming from first contacts of the immobilized cells with the implant via the pores of the composite from the beginning a friction-fit connection between the bone and implant is to develop by the proceeding dissolution of the individual phases. The time history of the dissolution of the composite layer is to simply characterize by three sections. In the section I the greatest local increase of the concentration of calcium and phosphate ions available in the boundary layer between the implant and bone is substantially determined by the more easily soluble phases. In this section it must be ensured that a fibrous encapsulation of the implant does not occur, and thus enabling its immediate osteointegration. In the section II the more difficult soluble composite portion will determine the local ion budget, and in particular will assist the mineralization of the new bone tissue. In the section III the 5 entire composite is dissolved and substituted by a new bone. The implant is healed into the bone in a friction-fit manner. In case of need the osteoinductive additives and/ or antimicrobial agents will also be released from the composite.

6 Claims 1. Electrochemically deposited bioactive calcium phosphate composite layers on implants, characterized by a completely resorbable composite layer made of calcium phosphates of different solubility having such a nature which enables a local increase of the concentration of calcium and phosphate ions which is adapted to the healing process and is accelerating this, and a microporous structure of this composite layer which due to the capillary action effects immediate moistening of the composite with blood and tissue fluid. 2. Electrochemically deposited bioactive calcium phosphate composite layers according to claim 1, characterized in that said composite is controllably modifiable with regard to its phase composition and solubility during the deposition as well as by a subsequent treatment, and thus a controlled resorption of the composite layer is possible. 3. Electrochemically deposited bioactive calcium phosphate composite layers according to claim 1, characterized by osteoinductive additives and/ or antimicrobial agents.

Claims

6. The claims defining the invention are as follows: 1. An electrochemically deposited, bioactive calcium phosphate composite layer for implants, said composite layer having a completely resorbable composite layer wherein the composite layer comprises the readily soluble calcium phosphate phases of young bone tissue, and less readily soluble calcium phosphate phases of mature bone arranged in a microporous structure. 2. The composite layer as claimed in claim 1 wherein the young bone tissue comprises monetite. 3. The composite layer as claimed in claim 1 or 2 wherein the young bone tissue comprises brushite. 4. The composite layer as claimed in any one of claims 1-3 wherein the readily soluble CaP phases are formed by monetite or brushite. 5. The composite layer as claimed in any one of claims 1-4 wherein the various CaP phases are matched in regard to structure, composition, and thickness to the respective bone tissue enclosing the implant. 6. The composite layer as claimed in any one of claims 1-5 including additives selected from the class consisting of osteoinductive additives and antimicrobial agents.
7. An electrochemically deposited bioactive calcium phosphate implantable composite layer substantially as herein described without reference to the prior art.
8. A process for producing an electrochemically deposited, bioactive calcium phosphate composite layer as claimed in any one of claims 1-7, characterised in that the composite layer is modified in controllable fashion with regard to its phase composition and/or solubility during its deposition and/or in subsequent treatment.
9. A process for producing an electrochemically deposited bioactive calcium phosphate implantable composite layer, said process being substantially as herein described.
10. An implant including the composite layer as claimed in any one of claims 1-7 or fabricated by the process as claimed in claim 8 or 9.
11. A method of utilising an electrochemically deposited, bioactive calcium phosphate implantable composite layer in bone re-generation, said method being substantially as herein described. 341 1B 7.
12. Bone regenerated in accordance with the method as claimed in claim 11. Dated this 28 h day of January 2003 DOT GMBH By HODGKINSONS OLD MCINNES Patent Attorneys for the Applicant 341 1B