Methods, compositions, and devices for the occlusion of cavities and passageways
Provided herein are methods, compositions, and devices for occluding cavities or passageways in a patient, in particular cavities or passageways in the cardiovascular system of a patient, such as the LAA of a patient's heart. The methods, compositions, and devices can be used to percutaneously occlude the LAA, decreasing the risk of thromboembolic events associated with AF.
1. A method of forming an occlusive body in situ within the left atrial appendage (LAA) of a patient comprising injecting a fluid crosslinkable biomaterial into the LAA of the patient;
wherein the crosslinkable biomaterial conforms to the local anatomy of the LAA upon injection and reacts to form a biocompatible polymeric matrix that adopts the 3-dimensional shape of the patient's LAA cavity, thereby filling the patient's LAA cavity and preventing stagnation of blood therewithin;
wherein the crosslinkable biomaterial has a viscosity of about 1,000 cP or less when injected into the LAA of the patient; and
wherein the biocompatible polymeric matrix has a viscosity of at least about 50,000 cP and an elastic modulus of from about 0.01 kPa to about 100 kPa.
2. The method of claim 1 , wherein the crosslinkable biomaterial comprises a first precursor molecule and a second precursor molecule, and wherein the first precursor molecule comprises an oligomer or polymer having one or more nucleophilic groups, and the second precursor molecule comprises an oligomer or polymer having one or more conjugated unsaturated groups.
3. The method of claim 2 , wherein the first precursor molecule comprises a poly(alkylene oxide)-based oligomer or polymer having x nucleophilic groups, wherein x is an integer of from 2 to 6.
4. The method of claim 3 , wherein the first precursor molecule comprises pentaerythritol poly(ethylene glycol)ether tetrasulfhydryl.
5. The method of claim 2 , wherein the second precursor molecule comprises a biomacromolecule having y conjugated unsaturated groups, wherein y is an integer of from 2 to 25.
6. The method of claim 5 , wherein the second precursor molecule comprises dextran vinyl sulfone.
7. The method of claim 1 , wherein the crosslinkable biomaterial has a cure time of less than about 5 minutes.
8. The method of claim 1 , wherein the biocompatible polymeric matrix has a degradation rate such that about 40% or less by weight of the biocompatible polymeric matrix degrades within 90 days of curing.
9. The method of claim 1 , wherein the biocompatible polymeric matrix exhibits an equilibrium swelling ratio of from about 2 to about 8.
10. The method of claim 1 , wherein the biocompatible polymeric matrix has an elastic modulus of from about 8 kPa to about 12 kPa.
11. The method of claim 1 , wherein the crosslinkable biomaterial is injected into the LAA of the patient using a delivery catheter,
wherein the delivery catheter comprises:
a proximal region;
a distal region comprising a distal tip;
a first lumen extending from the proximal region to the distal region; and
an occluding element positioned in proximity to the distal tip.
12. The method of claim 11 , wherein the occluding element comprises an inflatable balloon configured to substantially seal the LAA when inflated.
13. The method of claim 1 , wherein the patient has a CHA 2 DS 2 -VASc score of 2 or more.
14. The method of claim 1 , wherein the patient is contraindicated for anticoagulation therapy.
15. The method of claim 1 , wherein the biocompatible polymeric matrix is retained within the patient's LAA cavity through interaction with the local anatomy.
16. The method of claim 1 , wherein the biocompatible polymeric matrix exhibits an equilibrium swelling ratio of greater than 0.
17. The method of claim 1 , wherein the biocompatible polymeric matrix reaches equilibrium swelling within about 72 hours.
18. The method of claim 1 , wherein the biocompatible polymeric matrix has a cure time of less than about 20 minutes.
19. The method of claim 1 , wherein the biocompatible polymeric matrix is not biodegradable.
20. A method of forming an occlusive body in situ within the LAA of a patient comprising injecting a fluid biomaterial into the LAA of the patient;
wherein the biomaterial conforms to the local anatomy of the LAA upon injection and cures to form an occlusive body that swells to fill and occupy the patient's LAA cavity;
wherein the biomaterial has a viscosity of about 1,000 cP or less when injected into the LAA of the patient; and
wherein the occlusive body has a viscosity of at least about 50,000 cP and an elastic modulus of from about 0.01 kPa to about 100 kPa.
21. A method of forming an occlusive body in situ within the LAA of a patient comprising injecting a fluid biomaterial into the LAA of the patient;
wherein the biomaterial cures in situ in the LAA to form a biocompatible polymeric matrix that conforms to an interior 3-dimensional shape of the patient's LAA cavity and occludes the patient's LAA cavity;
wherein the biomaterial has a viscosity of about 1,000 cP or less when injected into the LAA of the patient; and
wherein the biocompatible polymeric matrix has a viscosity of at least about 50,000 cP and an elastic modulus of from about 0.01 kPa to about 100 kPa.