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

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.

3D printing and biocompatibility study of a new biodegradable occluder for cardiac defect.

OBJECTIVE: To fabricate a biodegradable occluder for heart defect using the three-dimensional (3D) printing technique and evaluate its biosafety in an animal model. METHODS: Occluder samples were made by 3D printing technique using the self-developed lactide-sanya methyl carbonate-glycolide (PLLA-TMC-GA) co-polymer or PLTG as the bio-material. The biocompatibility (cytological and hematological) of the materials was evaluated by cytotoxicity experiments, hemolysis test, dynamic blood clotting test, and platelet adhesion test. Finally, the histocompatibility of the occluder was evaluated by implantation in a rabbit model. RESULTS: Occluder samples were printed satisfactorily. Cytotoxicity assay showed no significant toxicity of PLTG in the cells. Hemolysis test showed less than 5% hemolysis rate of PLTG indicating only a mild effect on the red blood cells. The dynamic coagulation test showed poor activation of endogenous clotting factors. PLTG resulted in lower platelet activation compared to PLLA, as indicated by the platelet adhesion test. Finally, no obvious tissue damage or necrosis was seen in the in vivo implantation experiment. CONCLUSION: A new PLTG-based biodegradable occluder for heart defects with good biocompatibility can be manufactured by the 3D printing technique.

Biocompatibility and in vivo degradation of chitosan based hydrogels as potential drug carrier.

Carboxymethyl chitosan-graft-polylactide (CMCS-PLA) and carboxymethyl chitosan (CMCS) hydrogels were prepared by using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride/N-hydroxysuccinimide (EDC/NHS) as crosslinking agent and catalyst at room temperature. The biocompatibility of the hydrogels was evaluated with the aim of assessing their potential as drug carrier. Various aspects of biocompatibility were considered, including MTT assay, agar diffusion test, release of lactate dehydrogenase (LDH), hemolytic test, plasma recalcification time (PRT), and dynamic clotting time. MTT assay showed that the cytotoxicity level of both hydrogels to L-929 cells was 0 or 1. The LDH release of CMCS and CMCS-PLA was 26 and 29%, respectively, which is slightly higher than that of the negative control (21%) and much lower than that of the negative control (87%). The hemolysis ratio of CMCS and CMCS-PLA was 1.4 and 1.7%, respectively, suggesting outstanding anti-hemolysis properties of both materials. The PRT value of CMCS and CMCS-PLA was higher by 77 and 99% than the value of the positive control. All the results revealed that the hydrogels present good cytocompatibility and hemocompatibility in vitro. In vivo degradation and tissue compatibility were evaluated by subcutaneous injection in the dorsal area of rats. CMCS and CMCS-PLA hydrogels were completely degraded and the inflammatory response also completely disappeared around hydrogels after 19 days in vivo. It is thus concluded that hydrogels formed of CMCS and CMCS-PLA with outstanding biocompatibility are promising as potential drug carrier.

A Rapidly Fabricated Microfluidic Chip for Cell Culture.

Microfluidic chips (µFC) are emerging as powerful tools in chemistry, biochemistry, nanotechnology and biotechnology. The microscale size, possibility of integration and high-throughput present huge technical potential to facilitate the research of cell behavior by creating in vivo-like microenvironments. Here, we have developed a new method for rapid fabrication of µFC with Norland Optical Adhesive 81 (NOA81) for multiple cell culture with high efficiency. The proposed method is more suitable for the early structure exploration stage of µFC than existing procedures since no templates are needed and fast fabrication methods are presented. Simple PDMS-NOA81-linked microvalves were embedded in the µFC to control or block the fluid flow effectively, which significantly broadened the applications of µFC. Various types of cells were integrated into the chip and normal viabilities were maintained up to 1 week. Besides, concentration gradient was generated to investigate the cells in the µFC responded to drug stimulation. The cells appeared different in terms of shape and proliferation that strongly demonstrated the potential application of our µFC in online drug delivery. The high biocompatibility of NOA81 and its facile fabrication (µFC) promise its use in various cell analyses, such as cell-cell interactions or tissue engineering.