Poly(1,4-Butylene Succinate)/Chitosan Degradable Material As A Cardiac Atrial Septal Defect Patch

Objective:As the most common one,Atrial Septal Defect(ASD)accounts for about 13-18% of congenital heart diseases.The traditional ASD closure materials are mainly nickel-titanium alloy materials.And this type of non-degradable materials implantation has been shown by Longitudinal studies to trigger increased risk of complications such as arrhythmias and blood clots.In comparison,the human body can completely absorb degradable materials after endothelialization is completed at the defect site,without any noticeable negative impact.Therefore,degradable material is the developing trend of tissue regeneration and repair.To date,the studies devoted to 3D printing technology to make degradable ASD patches have not been reported with significant progress in this field.Therefore,this study aims to explore the use of poly(1,4-butylene succinate,PBS)and chitosan(CS)composite materials for 3D printing to fabricate atrial septal defect repair pieces to fill in the defect.Methods:The PBS/CS composites were prepared by melting blending method.The materials were characterized by FTIR,SEM,DSC and water contact Angle.The surface morphology,thermal properties and hydrophilicity of PBS materials with different proportions of chitosan were compared.The feasibility of making atrial septal defect patch with PBS/CS blend was evaluated by 3D printer.The effects of PBS/CS on NIH/3T3 cell morphology,oxidative stress level,cell proliferation and apoptosis were respectively evaluated by Phalloidin stained cytoskeleton,Reactive Oxygen Species Assay Kit,CCK-8,and Annexin V-FITC kit.Finally,the rats were implanted in vivo,and HE staining was used to observe the inflammatory reaction of the implanted tissue.Results:PBS/CS melt blend was successfully prepared.FTIR and SEM results showed that PBS was compatible with CS,and 10%CS was relatively evenly dispersed in PBS.DSC results show that adding CS can change the thermal properties of PBS,the crystallinity of PBS increased by 1-2%,and the melting temperature of PBS decreased slightly.The addition of CS improved the hydrophilicity of PBS.With the increase of CS addition amount,the water contact Angle decreased 15-20%,indicating that the hydrophilicity of PBS/CS composite increased.The 3D printed PBS/CS atrial septal defect patch showed consistent aperture and smooth edge,which could be restored to original shape after folding in half.However,due to the low crystallization rate of the material,the printed patch had a certain deviation from the theoretical size,the actual size of patches’ pores decreases.The cells cultured with PBS/CS material extract were compared with those cultured without PBS/CS material extract,the cell morphology,intracellular oxidative stress level,cell proliferation,and apoptosis were statistically analyzed,and the results showed no significant statistical differences.HE staining of pathological sections showed no significant difference in the early tissue inflammatory reaction at the implantation site between the experimental and control groups.12 weeks after the implantation,the material was completely wrapped with tissue and cells adhered well.A decrease in volume was observed 24 weeks after implantation,indicating partial degradation of the material.Conclusion:PBS and CS have a certain compatibility,and the addition of CS improves the thermal performance and hydrophilicity of PBS.It is feasible to make PBS/CS blend material into atrial septal defect mesh by 3D printing technology,and the in vivo and in vitro experiments show that the material has no obvious biological toxicity.This study preliminarily completed the material characterization and biocompatibility test of the PBS/CS degradable material as a potential candidate for making the cardiac patch.It points out the orientation for further research on the composite material’s mechanical properties and in situ experiments in animals.