An innovative occluder for cardiac defect: 3D printing and a biocompatibility research based on self‐developed bioabsorbable material—LA–GA–TMC

Abstract

This study adopted the latest self-developed bioabsorbable material lactide-glycolide-1,3-trimethylene carbonate (LA-GA-TMC) and applied the three-dimensional (3D) printing technique to manufacture the occluder for cardiac septal defects, so as to realize the individualized treatment of cardiac septal defects. At the same time, its biosafety was evaluated, with an aim to establish foundation for futural large-scale animal experiment and clinical trial. The traditional "one-pot synthesis" was modified, and the "two-step synthesis method" was utilized to synthesize the LA-GA-TMC terpolymer at the lactide: glycolide: trimethylene carbonate ratio of 6:1:1.7. Afterward, the synthesized terpolymer was used as the raw material to fabricate the occluder model via using 3D printing technique. Then, its biocompatibility was comprehensively evaluated through cytocompatibility, blood compatibility, and histocompatibility. The occluder made from LA-GA-TMC 3D printing had favorable ductility and recoverability; besides, it possessed the temperature-control feature, and the relative cell proliferation rates in extract liquids at various concentrations were all >70%, suggesting that it had favorable cytocompatibility. Moreover, hemolytic experiment revealed that its hemolytic rate was <5%, dynamic blood coagulation experiment demonstrated that the sample material moderately activated the blood coagulation, and the above findings suggested that it had good blood compatibility. In addition, implanting experiment in vivo revealed that its histocompatibility was superior to the traditional nitinol and the emerging poly-L-lactic acid. It is completely feasible to manufacture the cardiac septal defects occluder based on the novel absorbable material LA-GA-TMC, which has favorable biocompatibility, through 3D printing technique and it possesses broad prospects in large-scale animal experiment and clinical trial.

Recent Development of Biodegradable Occlusion Devices for Intra-Atrial Shunts

“…One of the drawbacks of biodegradable septal defect occluders that leads to complications such as residual shunts, device embolization, valvular damage was the limited specification of device size and morphology. The three-dimensional (3D)/four-dimensional (4D) printing technology using BSMPs emerges as a promising option for the innovation of next-generation heart defect occluders, owing to its advantages of rapid prototyping, adaptive and controllable designing, and personalized customization, which can effectively recapitulate both the native physiochemical and biomechanical characteristics of the cardiac defect structure [ 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 ]. Jia H et al .…”

“…Sun Y et al . [ 140 , 141 ] introduced a novel 3D-printing biodegradable occluder for cardiac defect using self-developed lactide-glycolide-1,3-trimethylene carbonate (LA-GA-TMC). The occluder was double-disk dumbbell with a central, cylindrical waist with 2 mm in length and 4–10 mm in diameter.…”

Progress of biodegradable polymer application in cardiac occluders

“…In vitro experiments demonstrated good biocompatibility, while in vivo implantation experiments have shown that its degradability and tissue compatibility are better than that of PLLA. 180,181 Additionally, the combination of biodegradable shape memory materials with 3D printing technology has enabled the 4D printing of occluders. The new programmable cardiac occluders can be restored to their previously set working shape after implantation in the heart by applying specific stimuli, such as temperature change, magnetic field change, or microwave radiation.…”

“…One recent attempt to achieve these objectives is the development of a novel terpolymer material, poly‐ l ‐lactide‐1,‐3‐trimethylene carbonate‐glycolide (PLLA–TMC–GA), which is used to produce cardiac occluders with shape memory and temperature control characteristics via 3D printing technology. In vitro experiments demonstrated good biocompatibility, while in vivo implantation experiments have shown that its degradability and tissue compatibility are better than that of PLLA 180,181 . Additionally, the combination of biodegradable shape memory materials with 3D printing technology has enabled the 4D printing of occluders.…”