Medtronic, Inc.

Linda L Cahalan

Patrick T Cahalan

Michel L Verhoeven

Marc Hendriks

Benedicte Fouache

Edouard Koulik

Antoine N Camps

Jean A Woloszko

Vincent Larik

Mark W Torrianni

Mirian Gillissen

Ron Blezer

Benedicte Foache

Judith Vincent

Benedict Fouache

Verhoeven Michel

Theo Lindhout

An implantable device for reducing restenosis includes a structure including a polyamino acid component, wherein the polyamino acid component can be in the form of a coating or a film on the structure or it can be an integral part of the structure.

Implatable device including a polyamino acid component

A method of modifying the surface characteristics of a substrate having a surface with an amide-functional polymer thereon. The method involves contacting the amide-functional polymer with a source of hydroxide ions and a source of hypohalite ions at a temperature of at least about 20&deg; C. for a time effective to convert at least a portion of the amide-functional groups to amine-functional groups to form a substrate surface comprising an amine-functional polymer, wherein the hydroxide ions are present in a molar excess relative to the hypohalite ions and at a concentration of no more than about 0.1 M, based on the total volume of the reaction mixture. A biomolecule is attached to the resultant amine-functional polymer.

Method for attachment of biomolecules to surfaces through amine-functional groups

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 method of modifying the surface characteristics of a substrate, particularly a polymeric material. The method involves grafting ethylenically unsaturated monomers and attaching biomolecules, such as heparin, to the surface of the substrate, such as a polymeric material, in one step using an oxidizing metal, such as ceric ions.

One-step method for attachment of biomolecules to substrate surfaces

A method for making a medical device having a biomolecule immobilized on a substrate surface is provided. The method includes coating the substrate surface with an amino-functional polysiloxane; and contacting the amino-functional polysiloxane coated surface with a biomolecule under conditions effective to immobilize the biomolecule.

Method for attachment of biomolecules to surfaces of medical devices

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

To minimize the incidence and consequences of device related infection that occur after prosthetics implants of neuro-muscular stimulating devices, an infection resistant intra-muscular lead has been developed and is disclosed herein. Infection incidence has been decreased by using biomaterials able to release antibacterial drugs (gentamicin) at a controlled rate for the first 3-6 weeks after implant.

Intramuscular stimulation lead with enhanced infection resistance

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

A method of treating a patient with a medical device having immobilized heparin on a blood-contacting surface in which the covalently attached heparinized surface is provided with an adsorbed protein which may be activated by the immobilized heparin to block the coagulation of fibrinogen. Antithrombin III is the preferred adsorbed protein. The adsorbed protein is maintained on the immobilized heparin surface until the medical device is placed into contact with the patient's blood. When in contact with the patient's blood, the adsorbed protein will prevent initial thrombin formation at the biomaterial-blood interface. The preadsorption of ATIII is accomplished under conditions advantageous to maximum heparin/ATIII binding. When the preadsorbed surface comes in contact with whole blood, the maximum advantage of prophlactic properties of ATIII/heparin are obtained.

Method for making improved heparinized biomaterials

To minimize the incidence and consequences of device related infection that occur after prosthetics implants of neuro-muscular stimulating devices, an infection resistant intramuscular lead has been developed. Infection incidence has been decreased by using biomaterials able to release antibacterial drugs (gentamicin) at a controlled rate for the first 3-6 weeks after implant.

An improved spacer material for improving the biocompatibility of a biomaterial and a method for making it in which a polyalkylimine is covalently attached to an aminated substrate and combined with a crosslinking agent which is at least difunctional in aldehyde groups. The polyalkylimine can be for example, polyethyleneimine and the crosslinking agent can be, for example, glutaraldehyde. Preferably, the crosslinking agent is applied in dilute solution and at a pH suitable to accomplish light crosslinking of the polyalkylimine and also provide aldehyde linkages at the interface between the biomolecule and the spacer.

Biocompatability of solid surfaces

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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Geleen, Netherlands

Linda L Cahalan