Drug Loading And Its Release Reguladon Of TPU Airway Stent By 3D Priting

Objective:Airway stenosis is a common respiratory disease,resulting in respiratory disorders,severe asphyxia and even death.Airway stent implantation is a kind of minimally invasive interventional therapy commonly used in clinic,which will quickly relieve the symptoms of dyspnea.Because of its low requirements for cardiopulmonary function,it has become one of the important means of clinical treatment.However,there are some problems to be solved in the process of stent implantation,such as stent displacement,tissue infection and granulation tissue hyperplasia leading to repeated restenosis.In this paper,3D printing technology was used to design and prepare a personalized drug loaded airway stent with multi-layer structure to solve the displacement problem caused by the mismatch between the stent and the patient’s airway structure.And then,the drug loading structure of the stent can be loaded with anti-tumor drugs,which can expand the narrow airway at the same time,slow-release targeted local administration can inhibit the proliferation of granulation tissue,and solve the problems of repeated restenosis and infection in clinical treatment.The safety and effectiveness of the scaffolds were evaluated by in vitro cell experiment.Method:TPU/HM-531 scaffolds were prepared by melt blending with medical grade thermoplastic polyurethane(TPU)as substrate and HM-531 hydrophilic modifier.The microporous channels for drug release were constructed by the dissolution effect of hydrophilic modifier.The airway bracket with three-layer composite structure was designed by using the software of 3ds Max 2019,which was composed of inner layer,middle layer and outer layer.The nail like protrusions were distributed on the surface of the outer layer.The airway bracket with good appearance,complete structure and smooth surface was made by optimizing the 3D printing process.The effect of radial compression ratio on the mechanical properties of the airway bracket was studied.The loading scheme and release behavior of dexamethasone,paclitaxel and mitomycin C were studied to screen the optimal stent structure and drug loading scheme.Using Paclitaxel injection as reference sample,the release solution of paclitaxel airway stent on the 50 th day was tested in vitro to preliminarily evaluate its biological safety and the effectiveness of inhibiting tumor cells.Result:With the increase of HM-531 content,the melt index of the modified material increases,the equilibrium torque and contact angle decrease,and the tensile strength and elongation at break first increase and then decrease.When the content of HM-531 was 10.0%,the equilibrium torque,melt index and contact angle of the blends were 6.0N·m,37.08g/10 min and 21.79°,respectively.The modified material with tensile strength of 34.98 MPa,elongation at break of 939.71% and HM-531 content of7.5-10% has excellent comprehensive properties.There was only one melting peak and one crystallization peak in DSC curve,and only one glass transition temperature in DMA loss factor curve,which indicated that HM-531 had good compatibility with TPU.With the increase of HM-531 content,the melting peak and crystallization peak move to high temperature,and the glass transition temperature moves to low temperature,which indicates that HM-531 has a good plasticizing effect on TPU.It was found that the content of HM-531 increased,the time of water bath increased,the number of micropores increased,and the pore diameter increased.HM-531 dissolved from TPU matrix and constructed the microporous channel for drug release.Under the conditions of printing temperature 220 ℃,printing speed 5 mm/s,moving speed 120mm/s and retreating speed 10 mm/s,the airway stent with complete structure,unobstructed lumen,smooth outer surface and good effect was prepared.When the radial compression ratio is 20%,the radial support force,compressive strength and compressive elastic modulus are 156.16N,1.2MPa and 8.7MPa,respetively.Increasing the dosage of HM-531 can improve the drug release rate,changing the types of drug carriers(such as changing the molecular weight of PEG,combining peg with water)can regulate the drug release behavior,and the optimal scheme of paclitaxel drug loaded airway stent was screened out: the dosage of HM-531 in the outer layer of the stent was 10%,PEG 400 was the drug carrier,the drug concentration was 15mg/m L,and the drug release duration was up to 90days,the cumulative release was 52.97%.The concentration of paclitaxel was 0.03μg/m L The inhibition effect of CNE2 tumor cells was more than 0.06μg/m L The effect of Paclitaxel Injection on the activity of L929 fibroblasts was less than that of Paclitaxel injection.Conclusion : In this paper,TPU and its hydrophilic modified blend were used as scaffolds,and 3D printing technology was used to prepare airway scaffolds with excellent comprehensive performance,which had good radial support performance and could be loaded with paclitaxel and other drugs.The drug release behavior can be regulated by changing the dosage of hydrophilic modifier HM-531 and drug carrier.The simulated release duration of paclitaxel airway stent in vitro can reach the clinical requirement of 90 days.The release solution had little effect on the activity of fibroblasts and had good inhibitory effect on tumor cells.This study laid a good experimental foundation for the product development and clinical application of new airway stents.It is expected to solve the clinical problems such as stent displacement and repeated restenosis,and has a good clinical application prospect.