Study of Long-Term Biocompatibility and Bio-Safety of Implantable Nanogenerators

Abstract

Implantable nanogenerator (i-NG) has shown great promises for enabling self-powered implantable medical devices (IMDs). One essential requirement for practical i-NG applications is its long-term bio-compatibility and bio-safety. This paper presents a systematic study of polydimethylsiloxane (PDMS) and PDMS/Parylene-C packaged Polyvinylidene fluoride (PVDF) NGs implanted inside female ICR (Institute of Cancer Research) mice for up to six months. The PVDF NG had a stable in vitro output of 0.3 V when bended for 7200 cycles and an in vivo output of 0.1V under stretching. Multiple advanced imaging techniques, including computed tomography (CT), ultrasound, and photoacoustic were used to characterize the embedded i-NGs in vivo. The i-NGs kept excellent adhesion to the adjacent muscle surface, and exhibited stable electrical output during the entire examine period. No signs of toxicity or incompatibility were observed from the surrounding tissues, as well as from the whole body functions by pathological analyses and blood and serum test. The PDMS package was also able to effectively insulate the i-NG in biological environment with negligible stray currents at a pA scale. This series of in-vivo and in-vitro study confirmed the biological feasibility of using i-NG in vivo for biomechanical energy harvesting.

Keywords: Biocompatibility; Biomechanical energy harvesting; Implantable Nanogenerator; In Vivo imaging; PVDF.

Fig. 1.. NG fabrication and implantation.

(a) Schematic structure of a packaged PVDF i-NG. Inset is a photo of the actual device, where the scale bar is 5 mm. (b) In vitro voltage outputs of a packaged PVDF i-NG when deflected at a frequency of 2Hz. Inset schematically shows deflection direction. (c) Digital photos showing the typical surgery process of NG implantation (i)-(iii), and wound healing situations of the implantation area in the next day (iv) and after six months (v) post-surgery.

Fig. 2.. In vivo CT and ultrasound imaging of i-NGs in ICR mice body.

(a) CT 3D projection images of ICR mice with NG implanted on the top surface of deep muscle near the hip joint. The mouse on the right- and left-hand-side of each pair was implanted with a i-NG packaged by PDMS (yellow circle) and PDMS/Parylene-C (green circle), respectively. (b) Enlarged CT scans of PDMS packaged (left panel) and PDMS/Parylene-C packaged i-NGs (right panel). These devices were obtained after 24 weeks of implantation and cleaned before CT scan. (c) CT transverse images of ICR mice at the 12th week post implantation. The left and right images were from mice implanted with i-NGs packaged by PDMS (yellow circle), and PDMS/Parylene- C (green circle), respectively. (d) Ultrasound imaging of PDMS packaged i-NGs and the surrounding tissues. Images of static (i) and movement state (ii) were presented. (e) Ultrasound imaging of PDMS/Parylene-C packaged i-NGs and the surrounding tissues. Images of static (i) and movement state (ii) were presented.

Fig. 3.. H&E staining of regional tissue from skin to deep layer muscle.

Sham sample from a mouse without implantation (a) and sliced samples from mice implanted with PDMS- and Parylene-C-packaged NGs for 2 weeks (b and c), 4 weeks (d and e), 12 weeks (f and g), and 24 weeks (h and i), respectively. A gap between connective tissue and deep muscle was found in each mouse, which indicated the location of the i-NG.

Fig. 4.. Periodical blood and serum test results.

Blue and orange bars represented i-NGs packaged with PDMS and PDMS/Parylene-C, respectively. The normal range is marked in between two violet dashed lines. The inflammation factors including white lymphocytes (LYM), blood cells (WBC), monocytes (MON), neutrophile granulocyte (NEU) and neutrophile granulocyte percentage (NEU percentage). The red blood cells (RBC) and hemoglobin (HGB) were related to anemia. For other remaining values, the blood urea nitrogen (BUN), serum creatinine (SCr) are correlated to kidney function while aspartate transaminase (AST) and alanine transaminase (ALT) are linked to liver function. The changes of platelets (PLT) represented the coagulation function after surgery.

Fig. 5.. I-NG performance stability investigation.

(a) In vitro voltage outputs of PDMS and PDMS/Parylene-C packaged i-NGs after they were taken out from sacrificed mice at different time frames. (b) Stability of voltage outputs as a function of time for i-NGs with different packaging strategies. The purple and red bars represent i-NGs with PDMS and PDMS/Parylene- C package, respectively. (c) Leakage current test of PDMS-package NGs over 21 days. Upper figure is the input current signal (provided by the function generator). Bottom figure is the corresponding leakage current measured between the NG surface and ground.