Highly piezoelectric, biodegradable and flexible amino acid nanofibers for medical applications

Introduction:: Amino acid crystals are an attractive piezoelectric material as they have an ultra-high piezoelectric coefficient and possess an appealing safety profile for medical implant applications. Unfortunately, solvent-cast films made from glycine crystals, are brittle, quickly dissolve in body fluid, and lack of crystal orientation control, reducing the overall piezoelectric effect. We present a new material processing strategy to (1) create a biodegradable, flexible, and highly piezoelectric nanofiber mat of glycine crystals embedded inside polycaprolactone (PCL) matrix, and (2) employ this material to fabricate a biodegradable ultrasound transducer that can disrupt the blood-brain barrier (BBB) safely. The glycine-PCL film achieves outstanding and stable piezoelectric performance with a high ultrasound output of 334 kPa, which is three times larger than one generated by the state-of-the-art biodegradable transducers under the same applied input. The glycine-PCL nanofibers-based implantable device can facilitate the delivery of chemo-drug to the brain and significantly enhance the animal survival time (2-fold) in mice bearing orthotopic glioblastoma (GBM) model. The biodegradable piezoelectric glycine-PCL nanofiber film, presented herein, could offer an excellent strategy for GBM therapy and significant impacts on the medical implants field.


Materials and Methods:: β-glycine crystals were grown and embedded in a soft and flexible polymeric matrix of PCL via electrospinning. The piezoelectric performance was characterized utilized the impact test (measured output charge generated under applied force) and actuation test ( measured displacement under applied electric field). Material biocompatibility was assessed in vitro. The biodegradability and functionality of the device have been characterized in in vitro conditions (PBX at 37 C). In vivo studies were also performed to evaluate the long term biocompatibility of the implant ultrasound transducer and demonstrate its ability to facilitate the delivery of chemotherapy drug to the brain to treat glioblastoma.

Results, Conclusions, and Discussions:: We have shown that the glycine-PCL exhibits an outstanding and long-lasting piezoelectric performance of up to 19 pC/N. The material degrades over time. Besides it, the biocompatibility experiments confirm the materials' and implant devices' safety in vitro and in vivo. Furthermore, we demonstrated that the gly-PCL ultrasonic transducer enhances the delivery of chemotherapeutic drugs (e.g., Paclitaxel) to the mouse brain and improves the treatment efficacy of glioblastoma. Specifically, the animals receiving Paclitaxel following the sonication from the glycine-PCL device exhibited the best anti-GBM activity (determined based on the bioluminescence intensity of the tumor) among all groups. Furthermore, the Kaplan-Meier survival curve analysis demonstrated that the combined treatment of sonication from the glycine-PCL device and the formulated PTX significantly extended the survivability of the animal up to 72 days with a median survival time of 65 days, which is much longer than that of other sham groups as well as the negative control group.

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