Abstract: A medical lead having a lead body and a biocompatible cuff and especially suitable for use as a nerve electrode. In the preferred bipolar embodiment the lead body has two conductors running therethrough. The distal end is coupled to a pulse generator, the proximal end is coupled to the biocompatible cuff. The biocompatible cuff is cylindrical and is constructed from collagen. Preferably the collagen is multi-layer, i.e. the first portion is cross-linked to an amount greater than the second portion. Through such a construction the collagen promotes tissue ingrowth in the region proximate a nerve and does not permit tissue ingrowth in the region away from the nerve, e.g. the exterior of the cuff.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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 polyalkyaimine and also provide aldehyde linkages at the interface between the biomolecule and the spacer.

Abstract: A method for attaching a biomolecule having a plurality of carboxyl groups to an aminated solid surface by reacting the biomolecule with a carbodiimide to effect an activation of the carboxyl groups of the biomolecule, reacting the carbodiimide activated biomolecule with the solid surface to covalently bind the biomolecule to the aminated solid surface, and then selectively restoring carboxyl groups to the biomolecule. The selective restoration of carboxyl groups can be carried out by mild hydrolysis and restores the functionality of the biomolecule. The method is "selective" since the bonds between the biomolecule and the aminated solid surface remain intact.

Abstract: 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 polyalkylizine 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.