Study of biodegradable occluder of atrial septal defect in a porcine model.

OBJECTIVE: To evaluate the safety and feasibility of a modified poly(l-lactic acid) (PLLA) atrial septal defect (ASD) occluder. METHODS: Forty-five piglets were divided into two groups: an experimental group (n = 27) and a control group (n = 18). The experimental group underwent percutaneous implantation of a modified PLLA ASD device while the control group underwent percutaneous implantation of a widely used metal ASD device. X-ray imaging, transthoracic echocardiography (TTE), electrocardiogram (ECG), histopathology and electron microscopic examination were performed at 7 days, 1, 3, 6, and 12 months after implantation. RESULTS: Twenty-seven experimental piglets and 18 control piglets were all successfully implanted with modified biodegradable and metal ASD devices, respectively. While both devices exhibited very good occluding effects, the modified PLLA ASD devices were completely endothelialized at 3 months after implantation, and the endothelialization appeared to be more complete compared to the control group. Degradation of the PLLA devices was noted at 12 months follow-up with no loss of integrity at the atrial septum. CONCLUSION: This animal model with implanting of the occluders was effective and not associated with complications. The modified PLLA ASD devices are more controllable and practical than our previous devices. The implanted devices demonstrated good endothelialization and degradability in short and moderate term follow-up. Long-term studies are now underway to further evaluate the biodegradability of this novel device.

A Novel-Design Poly-L-Lactic Acid Biodegradable Device for Closure of Atrial Septal Defect: Long-Term Results in Swine.

OBJECTIVES: The aim of this study is to evaluate the long-term effectiveness and safety of a self-expandable, double-disk biodegradable device made of poly-L-lactic acid (PLLA) for closure of atrial septal defects (ASDs) in swine. METHODS: ASDs were created by transseptal needle puncture followed by balloon dilatation in 20 piglets. The experimental group comprised 18 animals, while the remaining 2 animals were used as controls. Effectiveness and safety were evaluated by rectal temperature, leukocyte count, chest radiography, electrocardiogram, transthoracic echocardiography (TTE), intracardiac echocardiography (ICE), and histologic studies. Animals were followed up at 1, 3, 6, and 12 months. RESULTS: An ASD model was successfully created in 19 animals; 1 piglet died during the procedure. The ASD diameters that were created ranged from 5 to 6.4 mm. Devices were successfully implanted in 17 animals. No animal died during the follow-up studies. Rectal temperatures and electrocardiograms were normal at follow-up, while leukocyte counts transiently increased from 1 to 6 months. Radiography, TTE, ICE, and macroscopic studies demonstrated that PLLA occluders were positioned well, with no shifting, mural thrombus formation, or atrioventricular valve insufficiency. Histologic evaluations showed that PLLA devices were partially degraded in the follow-up study. CONCLUSIONS: ASD closure with the novel PLLA biodegradable device is safe and effective. Longer-term studies are needed to evaluate long-term biodegradability.

A Facile Composite Strategy to Prepare a Biodegradable Polymer Based Radiopaque Raw Material for "Visualizable" Biomedical Implants.

Enabling a biodegradable polymer radiopaque under X-ray is much desired for many medical devices. Physical blending of a present biodegradable polymer and a commercialized medical contrast agent is convenient yet lacks comprehensive fundamental research. Herein, we prepared a biodegradable polymer-based radiopaque raw material by blending poly(l-lactic acid) (PLLA or simply PLA) and iohexol (IHX), where PLA constituted the continuous phase and IHX particles served as the dispersed phase. The strong X-ray adsorption of IHX enabled the composite radiopaque; the hydrolysis of the polyester and the water solubility of the contrast agent enabled the composite biodegradable in an aqueous medium. The idea was confirmed by in vitro characterizations of the resultant composite, in vivo subcutaneous implantation in rats up to 6 months, and the clear visualization of a part of a biodegradable occluder in a Bama piglet under X-ray. We also found that the crystallization of PLA was significantly enhanced in the presence of the solid particles, which should be taken into consideration in the design of an appropriate biomaterial composite because crystallization degree influences the biodegradation rate and mechanical property of a material to a large extent. We further tried to introduce a small amount of poly(vinylpyrrolidone) into the blend of PLA and IHX. Compared to the bicomponent composite, the tricomponent one exhibited decreased modulus and increased elongation at break and tensile strength. This paves more ways for researchers to select appropriate raw materials according to the regenerated tissue and the application site.

Surface modification to enhance cell migration on biomaterials and its combination with 3D structural design of occluders to improve interventional treatment of heart diseases.

The dominant source of thromboembolism in heart comes from the left atrial appendage (LAA). An occluder can close LAA and significantly reduce the risk of strokes, particularly for those patients with atrial fibrillation. However, it is technically challenging to fabricate an LAA occluder that is appropriate for percutaneous implantation and can be rapidly endothelialized to accomplish complete closure and avoid severe complication. Hypothesizing that a fast migration rate of endothelial cells on the implant surface would lead to rapid endothelialization, we fabricated an LAA occlusion device for interventional treatment with a well-designed 3D architecture and a nanoscale 2D coating. Through screening of biomaterials surfaces with cellular studies in vitro including cell observations, qPCR, RNA sequencing, and implantation studies in vivo, we revealed that a titanium-nitrogen nanocoating on a NiTi alloy promoted high migration rate of endothelial cells on the surface. The effectiveness of this first nanocoating LAA occluder was validated in animal experiments and a patient case, both of which exhibited successful implantation, fast sealing and long-term safety of the device. The mechanistic insights gained in this study will be useful for the design of medical devices with appropriate surface modification, not necessarily for improved cell adhesion but sometimes for enhanced cell migration.

Biodegradable polymeric occluder for closure of atrial septal defect with interventional treatment of cardiovascular disease.

The next-generation closure device for interventional treatment of congenital heart disease is regarded to be biodegradable, yet the corresponding biomaterial technique is still challenging. Herein, we report the first fully biodegradable atrial septal defect (ASD) occluder finally coming into clinical use, which is made of biodegradable poly(l-lactic acid) (PLLA). We characterized the physico-chemical properties of PLLA fibers as well as the raw polymer and the operability of the as-fabricated occluders. Cell behaviors on material were observed, and in vivo fiber degradation and inflammatory responses were examined. ASD models in piglets were created, and 44 PLLA ASD occluders were implanted via catheter successfully. After 36 months, the PLLA ASD occluders almost degraded without any complications. The mechanical properties and thickness between newborn and normal atrial septum showed no significant difference. We further accomplished the first clinical implantation of the PLLA ASD occluder in a four-year boy, and the two-year follow-up up to date preliminarily indicated safety and feasibility of such new-generation fully biodegradable occluder made of synthetic polymers.