Biomimetic calcium phosphate implant coatings and methods for making the same
First Claim
1. A method of making a biomimetic calcium phosphate coating on the surface of a metal implant comprising the sequential steps of(1) chemisorbing a nucleating agent onto the surface of the metal implant comprising the steps of(a) oxidizing the implant by soaking the implant in a solution of hydrogen peroxide;
- and(b) soaking the implant in a solution comprising a nucleating agent;
(2) decanting the excess solution comprising the nucleating solution;
(3) soaking the metal implant in a solution comprising calcium chloride;
(4) washing and drying the metal implant;
(5) for a period of 5-7 days soaking the metal implant in a sterile, deaerated coating solution comprising calcium and phosphate in concentrations sufficient to form calcium phosphate crystals on the metal implant and a trace amount of the nucleating agent, wherein the solution is stirred and changed daily;
(6) rinsing the metal implant; and
(7) drying the metal implant.
1 Assignment
0 Petitions
Accused Products
Abstract
This invention encompasses porous, nanocrystalline, biomimetic calcium phosphate coatings of the order of 2-30 microns that can be grown on metal implants. The chemical surface treatments and methods for making the calcium phosphate coatings are disclosed. Post treatment with dilute hydrogels such as phema reinforce the inorganic structure and enhance the mechanical strength of the coatings. Methods are also disclosed for adsorbing or covalently attaching growth factor proteins to derivatives of the hydrogel coated calcium phosphate coatings. Such hydrogel reinforced calcium phosphate coatings show equivalent bone tissue growth as the currently used implants and are easily resorbed. This property in combination with the immobilized growth factors is expected to enhance the process of osseointegration of the disclosed coatings.
258 Citations
87 Claims
-
1. A method of making a biomimetic calcium phosphate coating on the surface of a metal implant comprising the sequential steps of
(1) chemisorbing a nucleating agent onto the surface of the metal implant comprising the steps of (a) oxidizing the implant by soaking the implant in a solution of hydrogen peroxide; - and
(b) soaking the implant in a solution comprising a nucleating agent; (2) decanting the excess solution comprising the nucleating solution; (3) soaking the metal implant in a solution comprising calcium chloride; (4) washing and drying the metal implant; (5) for a period of 5-7 days soaking the metal implant in a sterile, deaerated coating solution comprising calcium and phosphate in concentrations sufficient to form calcium phosphate crystals on the metal implant and a trace amount of the nucleating agent, wherein the solution is stirred and changed daily; (6) rinsing the metal implant; and (7) drying the metal implant. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19)
- and
-
20. A method of reinforcing the strength of a calcium phosphate coated metal implant with a hydrogel polymer comprising the sequential steps of
(1) heating the calcium phosphate coated metal implant at 350° - C.,
(2) soaking the metal implant in a solution comprising a hydrogel polymer; and (3) drying the implant at 50-60°
C. overnight. - View Dependent Claims (21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36)
- C.,
-
37. The method of reinforcing the strength of a calcium phosphate coated metal implant with a copolymerized hydrogel comprising the sequential steps of:
-
(1) making a copolymer of a hydrogel; (2) purifying the copolymerized hydrogel in a non-solvent; (3) drying the copolymerized hydrogel as a powder; (4) heating the calcium phosphate coated metal implant at 350°
C.;(5) soaking the metal implant in a solution of the copolymerized hydrogel; and (6) drying the metal implant at 50-60°
C. overnight. - View Dependent Claims (38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55)
-
- 56. A method of imbibing a growth factor into a reinforcing hydrogel polymer comprising the step of soaking a nanocrystalline calcium phosphate coated implant reinforced with a 2% (w/v) solution of the hydrogel polymer in a dilute solution of growth factor.
-
59. A kit useful for in situ coupling or absorption of growth factor proteins onto a calcium phosphate coated metal implant surface prior to implantation surgery, the kit comprising one or more containers comprising:
-
(1) a nanocrystalline calcium phosphate coated metal implant that is to be surgically implanted into a patient; (2) a 2% (w/v) solution of a reactive hydrogel polymer dissolved in a suitable solvent; and (3) a solution of growth factor proteins. - View Dependent Claims (60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 86, 87)
-
-
76. A method of making activated hydrogel polymers for coupling growth factor proteins, wherein the hydrogel reinforces calcium phosphate coatings on implants, comprising the steps of
(1) activating the hydrogel polymer by copolymerizing the hydrogel polymer with a spacer group molecule, wherein the spacer group molecule has a protein reactive functional group, (2) coupling a growth factor protein to the spacer group molecule at the protein reactive functional group.
Specification