Surgical Fastener with Broad Spectrum MMP Inhibitors
Methods and devices are provided for promoting wound healing. In general, surgical staplers and staple components are provided having an effective amount of at least one broad spectrum matrix metalloproteinase (MMP) inhibitor being effective to prevent MMP-mediated extracellular matrix degeneration during wound healing in tissue.
1 . A staple cartridge assembly for use with a surgical stapler, comprising:
a cartridge body having a plurality of staple cavities, each staple cavity having one of a plurality of surgical staples disposed therein; and
an effective amount of at least one broad spectrum matrix metalloproteinase (MMP) inhibitor being effective to prevent MMP-mediated extracellular matrix degeneration during wound healing in the tissue in a predetermined manner.
2 . The assembly of claim 1 , wherein the at least one broad spectrum MMP inhibitor is disposed on at least a portion of the plurality of staples.
3 . The assembly of claim 1 , wherein the MMP inhibitor inhibits at least five of MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP12, MMP13, MMP14, and MMP16.
4 . The assembly of claim 3 , wherein the MMP inhibitor comprises an anti-inflammatory agent.
5 . The assembly of claim 4 , wherein the MMP inhibitor is GM6001 (ilomastat).
6 . The assembly of claim 3 , wherein the MMP inhibitor is a tetracycline class antibiotic.
7 . The assembly of claim 6 , wherein the tetracycline class antibiotic is doxycycline or minocycline.
8 . The assembly of claim 3 , wherein the MMP inhibitor is one or more inhibitors selected from the group consisting of rebimastat, batimastat (BB-94), BB-1101, CGS-27023-A, marimastat, ONO-4817, Ro 28-2653, and SB-3CT.
9 . The assembly of claim 1 , wherein the MMP inhibitor inhibits four or less of MMP1, MMP2, MMP3, MMP9, MMP9, MMP12, MMP13, MMP14, and MMP16.
10 . The assembly of claim 9 , wherein the MMP inhibitor is one or more inhibitors selected from the group consisting of MMI-166, tanomastat, cipemastat, MMI-270, ABT-770, prinomastat, tetrahydropyran, RS-130830, and 239796-97-5.
11 . The assembly of claim 1 , further comprising a biocompatible adjunct material releasably retained on the cartridge body and configured to be delivered to tissue by deployment of the staples in the cartridge body, wherein the MMP inhibitor is encapsulated on the adjunct material by an absorbable polymer or is attached as a pendant molecule on the biocompatible adjunct material.
12 . A method for temporarily inhibiting wound healing at a surgical site immediately following surgical stapling of tissue by a surgical stapler, comprising:
engaging tissue between a cartridge assembly and an anvil of an end effector; and
actuating the end effector to eject staples from the cartridge assembly into the tissue;
wherein at least one of a portion of the plurality of staples include an effective amount of at least one broad spectrum matrix metalloproteinase (MMP) inhibitor, and wherein release of the MMP inhibitor prevents MMP-mediated extracellular matrix degeneration during wound healing in the tissue in a predetermined manner.
13 . The method of claim 12 , wherein the MMP inhibitor inhibits at least five of MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP12, MMP13, MMP14, and MMP16.
14 . The method of claim 13 , wherein the MMP inhibitor is one or more inhibitors selected from the group consisting of rebimastat, batimastat (BB-94), doxycycline, minocycline, GM6001 (ilomastat) and BB-1101, CGS-27023-A, marimastat, ONO-4817, Ro 28-2653, and SB-3CT.
15 . The method of claim 12 , wherein the MMP inhibitor is released immediately following delivery to the tissue.
16 . The method of claim 12 , wherein the MMP inhibitor inhibits four or less of inhibits at least five of MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP12, MMP13, MMP14, and MMP16.
17 . The method of claim 16 , wherein the MMP inhibitor is one or more inhibitors selected from the group consisting of MMI-166, tanomastat, cipemastat, MMI-270, ABT-770, prinomastat, tetrahydropyran, RS-130830, and 239796-97-5.
18 . The method of claim 13 , wherein the assembly further comprises a biocompatible adjunct material releasably retained on the cartridge body and configured to be delivered to tissue by deployment of the staples in the cartridge body, and wherein the MMP inhibitor is encapsulated on the adjunct material by an absorbable polymer or is attached as a pendant molecule on the biocompatible adjunct material.
19 . The method of claim 18 , wherein the MMP inhibitor releases from the adjunct material from 1 to 3 days following delivery to the tissue.
20 . The method of claim 13 , wherein the tissue is colon tissue.