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

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Abstract

Amino acid crystals are an attractive piezoelectric material as they have an ultrahigh piezoelectric coefficient and have 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 crystal orientation control, reducing the overall piezoelectric effect. Here, we present a material processing strategy to create biodegradable, flexible, and piezoelectric nanofibers of glycine crystals embedded inside polycaprolactone (PCL). The glycine-PCL nanofiber film exhibits stable piezoelectric performance with a high ultrasound output of 334 kPa [under 0.15 voltage root-mean-square (Vrms)], which outperforms the state-of-the-art biodegradable transducers. We use this material to fabricate a biodegradable ultrasound transducer for facilitating the delivery of chemotherapeutic drug to the brain. The device remarkably enhances the animal survival time (twofold) in mice-bearing orthotopic glioblastoma models. The piezoelectric glycine-PCL presented here could offer an excellent platform not only for glioblastoma therapy but also for developing medical implantation fields.

Abstract

Biodegradable piezoelectric glycine-based nanofiber transducer facilitates the delivery of chemotherapeutics to the brain.

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Most cited references 82

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The blood–brain barrier and blood–tumour barrier in brain tumours and metastases

Costas Arvanitis, Gino Ferraro, Rakesh Jain (2019)

For a blood-borne cancer therapeutic agent to be effective, it must cross the blood vessel wall to reach cancer cells in adequate quantities, and it must overcome the resistance conferred by the local microenvironment around cancer cells. The brain microenvironment can thwart the effectiveness of drugs against primary brain tumours as well as brain metastases. In this Review, we highlight the cellular and molecular components of the blood-brain barrier (BBB), a specialized neurovascular unit evolved to maintain brain homeostasis. Tumours are known to compromise the integrity of the BBB, resulting in a vasculature known as the blood-tumour barrier (BTB), which is highly heterogeneous and characterized by numerous distinct features, including non-uniform permeability and active efflux of molecules. We discuss the challenges posed by the BBB and BTB for drug delivery, how multiple cell types dictate BBB function and the role of the BTB in disease progression and treatment. Finally, we highlight emerging molecular, cellular and physical strategies to improve drug delivery across the BBB and BTB and discuss their impact on improving conventional as well as emerging treatments, such as immune checkpoint inhibitors and engineered T cells. A deeper understanding of the BBB and BTB through the application of single-cell sequencing and imaging techniques, and the development of biomarkers of BBB integrity along with systems biology approaches, should enable new personalized treatment strategies for primary brain malignancies and brain metastases.

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Fiber/Fabric‐Based Piezoelectric and Triboelectric Nanogenerators for Flexible/Stretchable and Wearable Electronics and Artificial Intelligence

Kai Dong, Xiao Peng, Zhong Wang (2019)

Integration of advanced nanogenerator technology with conventional textile processes fosters the emergence of textile-based nanogenerators (NGs), which will inevitably promote the rapid development and widespread applications of next-generation wearable electronics and multifaceted artificial intelligence systems. NGs endow smart textiles with mechanical energy harvesting and multifunctional self-powered sensing capabilities, while textiles provide a versatile flexible design carrier and extensive wearable application platform for their development. However, due to the lack of an effective interactive platform and communication channel between researchers specializing in NGs and those good at textiles, it is rather difficult to achieve fiber/fabric-based NGs with both excellent electrical output properties and outstanding textile-related performances. To this end, a critical review is presented on the current state of the arts of wearable fiber/fabric-based piezoelectric nanogenerators and triboelectric nanogenerators with respect to basic classifications, material selections, fabrication techniques, structural designs, and working principles, as well as potential applications. Furthermore, the potential difficulties and tough challenges that can impede their large-scale commercial applications are summarized and discussed. It is hoped that this review will not only deepen the ties between smart textiles and wearable NGs, but also push forward further research and applications of future wearable fiber/fabric-based NGs.

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Mechanical properties and cell cultural response of polycaprolactone scaffolds designed and fabricated via fused deposition modeling.

D W Hutmacher, T Schantz, I Zein … (2001)

A number of different processing techniques have been developed to design and fabricate three-dimensional (3D) scaffolds for tissue-engineering applications. The imperfection of the current techniques has encouraged the use of a rapid prototyping technology known as fused deposition modeling (FDM). Our results show that FDM allows the design and fabrication of highly reproducible bioresorbable 3D scaffolds with a fully interconnected pore network. The mechanical properties and in vitro biocompatibility of polycaprolactone scaffolds with a porosity of 61 +/- 1% and two matrix architectures were studied. The honeycomb-like pores had a size falling within the range of 360 x 430 x 620 microm. The scaffolds with a 0/60/120 degrees lay-down pattern had a compressive stiffness and a 1% offset yield strength in air of 41.9 +/- 3.5 and 3.1 +/- 0.1 MPa, respectively, and a compressive stiffness and a 1% offset yield strength in simulated physiological conditions (a saline solution at 37 degrees C) of 29.4 +/- 4.0 and 2.3 +/- 0.2 MPa, respectively. In comparison, the scaffolds with a 0/72/144/36/108 degrees lay-down pattern had a compressive stiffness and a 1% offset yield strength in air of 20.2 +/- 1.7 and 2.4 +/- 0.1 MPa, respectively, and a compressive stiffness and a 1% offset yield strength in simulated physiological conditions (a saline solution at 37 degrees C) of 21.5 +/- 2.9 and 2.0 +/- 0.2 MPa, respectively. Statistical analysis confirmed that the five-angle scaffolds had significantly lower stiffness and 1% offset yield strengths under compression loading than those with a three-angle pattern under both testing conditions (p < or = 0.05). The obtained stress-strain curves for both scaffold architectures demonstrate the typical behavior of a honeycomb structure undergoing deformation. In vitro studies were conducted with primary human fibroblasts and periosteal cells. Light, environmental scanning electron, and confocal laser microscopy as well as immunohistochemistry showed cell proliferation and extracellular matrix production on the polycaprolactone surface in the 1st culturing week. Over a period of 3-4 weeks in a culture, the fully interconnected scaffold architecture was completely 3D-filled by cellular tissue. Our cell culture study shows that fibroblasts and osteoblast-like cells can proliferate, differentiate, and produce a cellular tissue in an entirely interconnected 3D polycaprolactone matrix. Copyright 2001 John Wiley & Sons, Inc.

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Author and article information

Contributors

Meysam T. Chorsi:

ORCID: https://orcid.org/0000-0002-2633-9200

Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing - original draftRole: Writing - review & editing

Thinh T. Le:

ORCID: https://orcid.org/0000-0002-8180-2077

Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: VisualizationRole: Writing - original draftRole: Writing - review & editing

Feng Lin:

ORCID: https://orcid.org/0000-0002-2700-3573

Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: ValidationRole: VisualizationRole: Writing - original draftRole: Writing - review & editing

Tra Vinikoor:

ORCID: https://orcid.org/0000-0002-7637-6296

Role: InvestigationRole: MethodologyRole: ResourcesRole: ValidationRole: Writing - review & editing

Ritopa Das:

ORCID: https://orcid.org/0000-0001-7297-1998

Role: InvestigationRole: MethodologyRole: ValidationRole: Writing - original draft

James F. Stevens: Role: Formal analysisRole: InvestigationRole: Resources

Caitlyn Mundrane: Role: Writing - original draft

Jinyoung Park:

ORCID: https://orcid.org/0000-0003-0943-3649

Role: InvestigationRole: SoftwareRole: Validation

Khanh T. M. Tran:

ORCID: https://orcid.org/0000-0002-5331-4068

Role: Writing - original draft

Yang Liu:

ORCID: https://orcid.org/0000-0003-1655-828X

Role: Formal analysisRole: InvestigationRole: Project administrationRole: ResourcesRole: ValidationRole: VisualizationRole: Writing - original draft

Jacob Pfund:

ORCID: https://orcid.org/0000-0001-6745-489X

Role: Investigation

Rachel Thompson: Role: Investigation

Wu He: Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ResourcesRole: ValidationRole: VisualizationRole: Writing - original draftRole: Writing - review & editing

Menka Jain:

ORCID: https://orcid.org/0000-0002-2264-6895

Role: Data curationRole: Formal analysisRole: InvestigationRole: SupervisionRole: ValidationRole: Writing - original draftRole: Writing - review & editing

M. Daniela Morales-Acosta:

ORCID: https://orcid.org/0000-0003-1145-9485

Role: InvestigationRole: Resources

Osama R. Bilal:

ORCID: https://orcid.org/0000-0003-3803-5084

Role: Data curationRole: Formal analysisRole: InvestigationRole: ResourcesRole: SupervisionRole: ValidationRole: Writing - review & editing

Kazem Kazerounian:

ORCID: https://orcid.org/0009-0004-7115-0070

Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: SoftwareRole: SupervisionRole: Writing - original draft

Horea Ilies:

ORCID: https://orcid.org/0009-0000-1038-4536

Role: ConceptualizationRole: Funding acquisitionRole: Project administrationRole: SupervisionRole: Writing - original draftRole: Writing - review & editing

Thanh D. Nguyen:

ORCID: https://orcid.org/0000-0003-0813-4807

Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: VisualizationRole: Writing - original draftRole: Writing - review & editing

Journal

Journal ID (nlm-ta): Sci Adv

Journal ID (iso-abbrev): Sci Adv

Journal ID (publisher-id): sciadv

Journal ID (hwp): advances

Title: Science Advances

Publisher: American Association for the Advancement of Science

ISSN (Electronic): 2375-2548

Publication date Collection: June 2023

Publication date (Electronic, pub): 14 June 2023

Volume: 9

Issue: 24

Electronic Location Identifier: eadg6075

Affiliations

[ ¹ ]Department of Mechanical Engineering, University of Connecticut, Storrs, CT 06269, USA.

[ ² ]Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, USA.

[ ³ ]Department of Physics, University of Connecticut, Storrs, CT 06269, USA.

[ ⁴ ]Flow Cytometry Facility, Center for Open Research Resources and Equipment, University of Connecticut, Storrs, CT 06269, USA.

[ ⁵ ]Institute of Materials Science, University of Connecticut, Storrs, CT 06269, USA.

Author notes

[* ]Corresponding author. Email: nguyentd@ 123456uconn.edu (T.D.N.); horea.ilies@ 123456uconn.edu (H.I.); kazem.kazerounian@ 123456uconn.edu (K.K.)

[†]

These authors contributed equally to this work.

[‡]

Present address: Center of Digital Dentistry, Department of Prosthodontics and National Engineering Research, Center of Oral Biomaterials and Digital Medical Devices, Peking University School and Hospital of Stomatology, Beijing 100081, PR China.

Author information

Meysam T. Chorsi https://orcid.org/0000-0002-2633-9200

Thinh T. Le https://orcid.org/0000-0002-8180-2077

Feng Lin https://orcid.org/0000-0002-2700-3573

Tra Vinikoor https://orcid.org/0000-0002-7637-6296

Ritopa Das https://orcid.org/0000-0001-7297-1998

Jinyoung Park https://orcid.org/0000-0003-0943-3649

Khanh T. M. Tran https://orcid.org/0000-0002-5331-4068

Yang Liu https://orcid.org/0000-0003-1655-828X

Jacob Pfund https://orcid.org/0000-0001-6745-489X

Menka Jain https://orcid.org/0000-0002-2264-6895

M. Daniela Morales-Acosta https://orcid.org/0000-0003-1145-9485

Osama R. Bilal https://orcid.org/0000-0003-3803-5084

Kazem Kazerounian https://orcid.org/0009-0004-7115-0070

Horea Ilies https://orcid.org/0009-0000-1038-4536

Thanh D. Nguyen https://orcid.org/0000-0003-0813-4807

Article

Publisher ID: adg6075

DOI: 10.1126/sciadv.adg6075

PMC ID: 10266740

PubMed ID: 37315129

SO-VID: 8ab2810b-c29c-4ada-9cda-519dc5a7deeb

Copyright © Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

History

Date received : 10 January 2023

Date accepted : 10 May 2023

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100000001, National Science Foundation;

Award ID: 1635103

Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;

Award ID: R21NS116095

Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;

Award ID: R01NS131310

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Copyeditor Vivian Hernandez

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

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Most cited references 82

The blood–brain barrier and blood–tumour barrier in brain tumours and metastases

Fiber/Fabric‐Based Piezoelectric and Triboelectric Nanogenerators for Flexible/Stretchable and Wearable Electronics and Artificial Intelligence

Mechanical properties and cell cultural response of polycaprolactone scaffolds designed and fabricated via fused deposition modeling.

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Cited by 8

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