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Objectives The authors investigate whether the combination of anti-CD34 antibody with DES is win-win cooperation. Background DES may reduce the risk of restenosis compared to bare-metal stents (BMS), but they were found to inhibit the healing process of intima. Methods Fifteen BMS, 17 DES, and 16 combined anti-CD34 antibody and DES were randomly implanted in the coronary arteries of 22 minipigs. Ten minipigs were followed up to 2 weeks. The stenting coronary segments were examined by histological examination and scanning electron microscopy after in vivo coronary angiography and intracoronary optical coherence tomography (OCT) examinations. The other 12 minipigs were followed up to 3 months. Coronary angiography and intracoronary OCT examination were performed in vivo and histological examination was performed on the stenting coronary segments. Results After 2 weeks, the neointimal covering level of the DES was lower than that in BMS, but the covering level of the combined stents was even better than the BMS. After 3 months, neointimal hyperplasia was significant in the BMS, but not in the other two types of stents. The in-stent late lumen loss of the combined stents even showed a decreasing tendency when compared with the DES. Conclusion The combination of anti-CD34 antibody and DES can not only well offset the short-term inhibitory effect on re-endothelialization but also slightly enhance the long-term antiproliferative effect.

Drug-eluting stents have shown an impressive reduction of in-stent restenosis for many years. However, stent thrombosis due to incomplete/late endothelialization has raised major safety concerns. To overcome these problems, we developed for the first time a polymer-free sirolimus-eluting antibody-coated stent (PFSEACS) by combining polymer free and endothelial progenitor cell-capture pro-healing approaches. In the first phase, the stents were prepared by loading sirolimus on the porous outer stent surface and directly fixing the anti-CD34 antibodies without any medium carriers on the blood contacting surface. The dose and elution of sirolimus, the amount and stability of anti-CD34 antibody immobilization, and the rate of CD34+ cell capture were evaluated. In the second phase, the stents were validated in an animal model of coronary arteries in pigs. The stent was observed to start collecting endothelial progenitor cells ~2 h after stent implantation and exhibited greatly enhanced endothelialization while maintaining an excellent anti-restenosis activity comparable to the polymer-free sirolimus-eluting stents. Overall, both in vitro and in vivo evaluations indicated that novel PFSEACSs exhibited facilitated endothelialization with excellent anti-restenosis activity and thus should merit further clinical studies.

To investigate the impact of the stents coated with sirolimus and anti-CD34 antibody on the short-term re-endothelialization and the long-term restenosis in Chinese Minipigs.Three different types of stents [bare-metal stent (BMS), sirolimus-eluting stent (SES) and anti-CD34 antibody and sirolimus-coated stent (ASES)] were randomly implanted in the coronary arteries of 22 Chinese Minipigs. At two weeks after stenting, coronary angiography and optical coherence tomography (OCT) were performed in 10 experimental animals. At three months after stenting, coronary angiography and OCT were performed in the remaining 12 experimental animals. Histopathologic examination was performed on the coronary artery segments containing stent after the animals were executed.(1) No in-stent thrombosis and parietal thrombus were found by coronary angiography, OCT and histopathologic examination at two weeks post stenting. OCT analysis showed that the covered ratio of stent struts by neointima in ASES group was higher than in SES group [(55.56 ± 35.27)% vs. (41.82 ± 23.28)%, P0.05]. The mean thickness of neointima in ASES group was significantly higher than in SES group [(89.0 ± 5.0) µm vs. (32.0 ± 4.9) µm, P0.01] and BMS group [(89.0 ± 5.0) µm vs. (44.0 ± 7.2) µm, P0.01]. Histopathologic and scanning electron microscopy examinations demonstrated that the covering level and quality of stent struts by neointima in BMS and ASES group were both better than in SES group. (2) At three months follow-up, quantitative coronary angiography analysis found that late in-stent lumen loss in ASES group was significantly lower than in BMS group [(0.18 ± 0.06) mm vs.(0.35 ± 0.06) mm, P0.05]. OCT analysis showed that the percent neointimal hyperplasia in ASES and SES group was significantly lower than in BMS group [(34.75 ± 2.64)% and (35.63 ± 2.07)% vs. (48.28 ± 3.25)%, both P0.01]. Histopathologic analysis demonstrated that the percent areal restenosis of ASES and SES group were both significantly lower than that of BMS group [(28.65 ± 5.64)% and (29.33 ± 6.07)% vs. (46.18 ± 8.25)%, both P0.05].The stents coated with anti-CD34 antibody and sirolimus can attenuate the inhibitory effect of sirolimus on the re-endothelialization at two weeks after stenting and the anti-hyperplasia effect of sirolimus at three months after stenting.