Morphology after coronary stenting demonstrates early thrombus formation and acute inflammation followed by neointimal growth. Medial injury and lipid core penetration by struts result in increased inflammation. Neointima increases as the ratio of stent area to reference lumen area increases. Deployment strategies that reduce medial damage and avoid stent oversizing may lower the frequency of in-stent restenosis.

Background-The purpose of this study was to determine the efficacy of stent-based delivery of sirolimus (SRL) alone or in combination with dexamethasone (DEX) to reduce in-stent neointimal hyperplasia. SRL is a potent immunosuppressive agent that inhibits SMC proliferation by blocking cell cycle progression. Methods and Results-Stents were coated with a nonerodable polymer containing 185 g SRL, 350 g DEX, or 185 g SRL and 350 g DEX. Polymer biocompatibility studies in the porcine and canine models showed acceptable tissue response at 60 days. Forty-seven stents (metal, nϭ13; SRL, nϭ13; DEX, nϭ13; SRL and DEX, nϭ8) were implanted in the coronary arteries of 16 pigs. The tissue level of SRL was 97Ϯ13 ng/artery, with a stent content of 71Ϯ10 g at 3 days. At 7 days, proliferating cell nuclear antigen and retinoblastoma protein expression were reduced 60% and 50%, respectively, by the SRL stents. After 28 days, the mean neointimal area was 2.47Ϯ1.04 mm 2 for the SRL alone and 2.42Ϯ1.04 mm 2 for the combination of SRL and DEX compared with the metal (5.06Ϯ1.88 mm 2 , PϽ0.0001) or DEX-coated stents (4.31Ϯ3.21 mm 2 , PϽ0.001), resulting in a 50% reduction of percent in-stent stenosis. Conclusions-Stent-based delivery of SRL via a nonerodable polymer matrix is feasible and effectively reduces in-stent neointimal hyperplasia by inhibiting cellular proliferation.

Background-Paclitaxel can inhibit vascular smooth muscle proliferation in vitro, and early studies suggest that paclitaxel may be useful in preventing restenosis.

SRL-eluting stents favorably modulate neointimal formation for 30 days in the porcine coronary model. Long-term inhibition of neointimal hyperplasia is not sustained presumably due to delayed cellular proliferation despite increased levels of the cyclin-dependent kinase p27(kip1) in the vessel wall.

The objectives of augmentation of the nucleus pulposus following disc removal are to prevent disc height loss and the associated biomechanical and biochemical changes. Flowable materials may be injected via a small incision, allowing minimally invasive access to the disc space. Fluids can interdigitate with the irregular surgical defects and may even physically bond to the adjacent tissue. Injectable biomaterials allow for incorporation and uniform dispersion of cells and/or therapeutic agents. Injectable biomaterials have been developed that may act as a substitute for the disc nucleus pulposus. Our work has focused on the evaluation of a recombinant protein copolymer consisting of amino acid sequence blocks derived from silk and elastin structural proteins as an injectable biomaterial for augmentation of the nucleus pulposus. This implant, NuCore TM Injectable Nucleus is being developed by Spine Wave (Shelton, CT). The NuCore

Early thrombus formation is minimal, and thrombus accounts for a small portion of subsequent neointimal formation. Smooth muscle cell proliferation and matrix formation are the major factors relating to neointimal formation in this proliferative model of restenosis. The evolution of neointimal formation after coronary stenting shows maximal smooth muscle cell proliferation at 7 days, with a decline to low levels by 28 days. Therefore, these data may be useful for developing effective therapies for restenosis.

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The differential response to the doses of continuous beta-particle irradiation used in this experimental model suggests a complex biological interaction of endovascular radiation and vascular repair after stent placement. Further study is required to determine the clinical potential for this therapy to prevent stent restenosis.