Experimental Study On The Treatment Of Benign Esophageal Stricture With Biodegradable Drug Eluting Scaffolds

Aim: To prepare and in vitro evaluate the physical properties and biocompatibility of a novel paclitaxel-poly(lactic-co-glycolic)acid(PTX-PLGA)coated magnesium-based composite scaffold,and to evaluate its efficacy and safety in the treatment of benign esophageal stenosis(BES)in animal experimentsMethod: Biodegradable PLGA and paclitaxel were mixed and coated on a magnesium wire woven scaffold to prepare a fully biodegradable drug-carrying stent.The radial strength was measured of the bare stent,the coated stent,and the expanded stent after compression,and placed into two phosphate buffers(PH=7.4/4.0)for in vitro degradation test and drug release test.The benign esophageal stricture model of rabbits was constructed by the corrosive injury and the fibroblasts from the stricture site were extracted.The biocompatibility of the scaffold and its inhibitory effect on the proliferation of fibroblasts were studied by co-culture the extract of the scaffold with the extracted fibroblasts.Finally,the stent was implanted into the animals to observe the opening of the esophagus and the occurrence of adverse events.Finally,the stents were implanted into the rabbit models,the patency of the esophagus was appraised and the incidence of adverse events were investigated.Result: PTX-PLGA membrane coated on magnesium can effectively delay corrosion and improve the radial support force of the stent.The radial support forces of bare stents,coated stents and stents after compression and balloon expansion were(32.56± 0.88)N,(82.64±9.25)N and(77.21±10.44)N,respectively.The radial force of the coated stent was significantly higher than that of the bare stent(P<0.05).In the two groups of phosphate buffer saline for 28 consecutive days,the cumulative drug release of the stent was(114.52±13.47)μg/mL(PH = 7.4)and(176.10±11.95)μg/mL(PH = 4.0).After cell culture with scaffold extract for 48 h,the apoptosis rate of non-drug-loaded coated scaffolds was(4.08±0.64)%,which had no statistical significance compared with the blank control group(3.00±0.84%)(P>0.05).The cell apoptosis rate of the coated scaffold group with 20% drug loading was(29.50±1.93)%,which was statistically different from the above two groups(P<0.05).In vivo evaluation,the esophageal tissue of the stent group showed no signs of cytotoxicity.Histological examination showed that the number of fibroblasts in the stent group was significantly reduced in the third week,and the submucosal and muscular layers were also thinned(P<0.05).Conclusion: PTX-PLGA coated magnesium stent has good biocompatibility,and can provide radial support for a certain period of time to maintain esophageal patency,and slowly degrade and release loaded PTX,and stably promote the apoptosis of fibroblasts.