Medtronic, Inc.

Benedicte Fouache

Patrick T Cahalan

Marc Hendriks

Linda L Cahalan

Michel L Verhoeven

Mark W Torrianni

Verhoeven Michel

Methods for making bioprosthetic devices made of collagen-based material having collagen amine groups and collagen carboxyl groups are provided. The methods include blocking at least a portion of the collagen amine groups with a blocking agent, activating at least a portion of the collagen carboxyl groups after blocking at least a portion of the collagen amine groups to form activated carboxyl groups, and contacting the activated collagen carboxyl groups with a polyfunctional spacer to crosslink the collagen-based material.

Process for making a bioprosthetic device

A medical device having a surface graft matrix comprising carboxyl-functional groups located on the device, the surface graft matrix comprising an outer portion; and one or more biomolecules covalently coupled to the surface graft matrix, wherein a majority of the biomolecules are located in the outer portion of the surface graft matrix. The surface graft matrix can also be loaded with a pharmaceutical agent.

Medical device with biomolecule-coated surface graft matrix

Method of modifying the surface of a medical device

A medical article having a metal or glass surface with the surface having an adherent coating of improved biocompatibility. The coating is made by first applying to the surface an silane compound having a pendant vinyl functionality such that the silane adheres to the surface and then, in a separate step, forming a graft polymer on the surface with applied vinylsilane such that the pendant vinyl functionality of the vinylsilane is incorporated into the graft polymer by covalent bonding with the polymer. Biomolecules may then be covalently attached to the base layer.

Biocompatible medical article and method

An improved method of making a medical device having immobilized heparin on a blood-contacting surface in which heparin is admixed with sufficient periodate to react with not more than two sugar units per heparin molecule in a buffer solution having a pH in the range of about 4.5-8. This mixture is reacted for at least 3 hours while protected from light and is then applied to the immobilized amine groups. This is an improvement over the prior art methods which included using an excess of periodate and then stopping the reaction at a desired point by the addition of glycerol since the conversion of only a few of the natural functional groups to aldehydes better preserves the antithrombotic bioeffectiveness of the heparin molecules bound to the surface. The invention also avoids the prior art steps of drying and reconstituting the heparin by providing a reacted mixture of heparin and periodate that can be stored as a stable liquid and applied directly to the aminated surface several days later.

Method for making heparinized biomaterials

An improved coating and spacer material for a medical device having a blood or tissue-contacting surface comprising a polyalkyleneimine layer which is crosslinked with a crosslinking agent which is at least difunctional in polymerizable vinyl groups which have adjacent strong electron-withdrawing groups and a biomolecule covalently bonded to the crosslinked polyalkyleneimine layer. For example, polyethyleneimine crosslinked with divinyl sulfone could be used. The resulting crosslinked spacer layer has improved uniformity and stability without materially limiting the covalent attachment of a biomolecule such as heparin.

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Maastricht, Netherlands

Benedicte Fouache