Geistlich Pharma Ag

Michael Alexander Bufler

Claudio Zihlmann

Cornel Imhof

Lothar Schlösser

Birgit Schafer

Birgit SCHÄFER

Collagen matrix granulate blend, and process for making and using a collagen matrix or granulate blend including collagen and particles of a biphasic calcium phosphate/hydroxyapatite (CAP/HAP) bone substitute material having a sintered CAP core and having its total external surface covered by at least one closed epitactically grown layer of nanocrystalline HAP deposited on the external surface of the sintered CAP core, whereby the epitactically grown nanocrystals have the same size and morphology as human bone mineral, wherein the closed epitactically grown layer of nanocrystalline HAP is transformed from the CAP on the external surface of the sintered CAP core has a non-homogeneous external surface comprising individual clusters of flat crystal platelets consisting of epitactically grown HAP nanocrystals and coarse areas between the individual clusters, whereby the percentage of the coarse areas between the individual clusters as measured by SEM is at least 20% of the total surface.

Collagen matrix or granulate blend of bone substitute material

A biphasic calcium phosphate/hydroxyapatite (CAP/HAP) bone substitute material having a sintered CAP core and a closed epitactically grown layer of nanocrystalline HAP deposited on the external surface of the sintered CAP core, wherein the closed epitactically grown layer of nanocrystalline HAP deposited on the external surface of the sintered CAP core has a homogeneous coarse external surface comprising flat crystal platelets, which shows an enhanced osteogenic response, a method of promoting bone formation, bone regeneration and/or bone repair by implanting the biphasic calcium phosphate/hydroxyapatite (CAP/HAP) bone substitute material, and a process of preparation thereof.

Bone substitute material

A collagen matrix, granulate blend, and process for making and using a collagen matrix or granulate blend including collagen and particles or granules of a biphasic calcium phosphate/hydroxyapatite (CAP/HAP) bone substitute material comprising a sintered CAP core and a closed epitactically grown layer of nanocrystalline HAP deposited on the external surface of the sintered CAP core, whereby the epitactically grown nanocrystals have the same size and morphology as human bone mineral, wherein the closed epitactically grown layer of nanocrystalline HAP deposited on the external surface of the sintered CAP core has a homogeneous coarse external surface comprising flat crystal platelets.

A biphasic calcium phosphate/hydroxyapatite (CAP/HAP) bone substitute material having a sintered CAP core and at least one closed epitactically grown layer of nanocrystalline HAP deposited on the external surface of the sintered CAP core, whereby the epitactically grown nanocrystals have the same size and morphology as human bone mineral, wherein the closed epitactically grown layer of nanocrystalline HAP deposited on the external surface of the sintered CAP core has a non-homogeneous external surface comprising individual clusters of flat crystal platelets consisting of epitactically grown HAP nanocrystals and coarse areas between the individual clusters, whereby the percentage of the coarse areas between the individual clusters as measured by SEM is at least 20% of the total surface, which material shows an increased capacity to induce bone formation, and a process of preparation thereof.

The invention relates to: &#x2014;a biomimetic collagen-hydroxyapatite composite material comprising an at least partially fibrous collagen scaffold including mature native collagen fibers possessing triple helicity as shown by Circular Dichroism Spectroscopy, wherein those mature native collagen fibers are at least partially covered with epitactically grown crystals of nanocrystalline hydroxyapatite, whereby the epitactically grown nanocrystals have the same morphology as human bone mineral and the same size as human bone mineral, i.e. a length of 30 to 50 nm and a width of 14 to 25 nm, &#x2014;a process of preparing the above biomimetic collagen-hydroxyapatite composite material comprising the steps of a) immersing an at least partially fibrous collagen scaffold including the above mature native collagen fibers in a saturated aqueous solution of saturated Ca/Hx-PO4to start the formation process of the composite implant material whereby epitactically grown nanocrystals will be formed on the mature native collagen fibers, the epitactically grown nanocrystals having the same morphology and same size as human bone mineral, b) stopping the formation process of the composite implant material by separating solid material from the aqueous solution, rinsing with water and drying, and c) optionally sterilizing the separated material coming from step b), as well as &#x2014;the use of the above biomimetic collagen-hydroxyapatite composite material as an implant or prosthesis for bone formation, bone regeneration, bone repair and/or bone replacement at a defect site in a human subject or in an animal, or as an implant for combined bone and cartilage regeneration.

Biomimetic collagen-hydroxyapatite composite material

The invention relates to: &#x2014;a porous biphasic calcium phosphate/hydroxyapatite (CAP/HAP) bone substitute material comprising a sintered CAP core and at least one uniform and closed epitactically grown layer of nanocrystalline HAP deposited on top of the sintered CAP core, whereby the epitactically grown nanocrystals have the same size and morphology as human bone mineral, i.e. a length of 30 to 46 nm and a width of 14 to 22 nm, which is impregnated with collagen fibers at a weight ratio of said collagen fibers to said porous biphasic calcium phosphate/hydroxyapatite (CAP/HAP) bone substitute material of at least 2%, &#x2014;a process of preparing the above porous CAP/HAP bone substitute material, which comprises (a) mixing a slurry of collagen fibers and a porous biphasic calcium phosphate/hydroxyapatite (CAP/HAP) bone substitute material comprising a sintered CAP core and at least one uniform and closed epitactically grown layer of nanocrystalline HAP deposited on top of the sintered CAP core, whereby the epitactically grown nanocrystals have the same size and morphology as human bone mineral, i.e. a length of 30 to 46 nm and a width of 14 to 22 nm, and (b) eliminating the water by vacuum suction, &#x2014;an implant which comprises a porous collagen matrix surrounding and impregnating particles or granules of porous biphasic calcium phosphate/hydroxyapatite (CAP/HAP) bone substitute material comprising a sintered CAP core and at least one uniform and closed epitactically grown layer of nanocrystalline HAP deposited on top of the sintered CAP core, whereby the epitactically grown nanocrystals have the same size and morphology as human bone mineral, i.e. a length of 30 to 46 nm and a width of 14 to 22 nm, &#x2014;the use of the above bone substitute material as implant or prosthesis for bone formation, bone regeneration, bone repair and/or bone replacement at a defect site in a human or animal.

The invention relates to: &#x2014;a biphasic calcium phosphate/hydroxyapatite (CAP/HAP) bone substitute material comprising a sintered CAP core and at least one uniform and closed epitactically grown layer of nanocrystalline HAP deposited on top of the sintered CAP core, whereby the epitactically grown nanocrystals have the same size and morphology as human bone mineral, i.e. a length of 30 to 46 nm and a width of 14 to 22 nm, &#x2014;a process of preparing the above CAP/HAP bone substitute material comprising the steps of a) preparing a sintered CAP core material, b) immersing the sintered CAP core material in an aqueous solution at a temperature between 10&#xb0; C. and 50&#xb0; C. to start the transformation process of CAP to HAP whereby a uniform and closed epitactic grown layer of nanocrystalline hydroxyapatite will be formed on the CAP core material surface, the epitactically grown nanocrystals having the same size and morphology as human bone mineral, c) stopping the transformation by separating solid material from the aqueous solution at a time when a uniform and closed coating of at least one nanocrystalline layer of HAP is present but before the transformation process is finished completely, and d) optionally sterilizing the separated material coming from step c), and &#x2014;the use of the above bone substitute material as implant or prosthesis for bone formation, bone regeneration, bone repair and/or bone replacement at a defect site in a human or animal.

Growing community of inventors

Emmenbruecke, Switzerland

Michael Alexander Bufler