Integrating Graphene Oxide-Hydrogels and Electrical Stimulation for Controlled Neurotrophic Factor Encapsulation: A Promising Approach for Efficient Nerve Tissue Regeneration

Alexandre Xavier Mendes; Lilith Caballero Aguilar; Adriana Teixeira do Nascimento; Serena Duchi; Mirren Charnley; David R Nisbet; Anita F Quigley; Robert M I Kapsa; Saimon Moraes Silva; Simon E Moulton

doi:10.1021/acsabm.4c00523

Integrating Graphene Oxide-Hydrogels and Electrical Stimulation for Controlled Neurotrophic Factor Encapsulation: A Promising Approach for Efficient Nerve Tissue Regeneration

ACS Appl Bio Mater. 2024 Jun 17;7(6):4175-4192. doi: 10.1021/acsabm.4c00523. Epub 2024 Jun 3.

Authors

Alexandre Xavier Mendes^{1

2}, Lilith Caballero Aguilar^{2

3

4}, Adriana Teixeira do Nascimento^{1

2}, Serena Duchi^{2

5}, Mirren Charnley^{6

7

8}, David R Nisbet^{2

3

4

9}, Anita F Quigley^{1

10

11}, Robert M I Kapsa^{1

2

10

11}, Saimon Moraes Silva¹², Simon E Moulton^{1

2

13}

Affiliations

¹ ARC Centre of Excellence for Electromaterials Science, School of Science, Computing and Engineering Technologies, Swinburne University of Technology, Melbourne, Victoria 3122, Australia.
² Aikenhead Centre for Medical Discovery, St Vincent's Hospital Melbourne, Melbourne, Victoria 3065, Australia.
³ The Graeme Clark Institute, Biomedical Engineering Department, Melbourne University, Melbourne, Victoria 3065, Australia.
⁴ Department of Biomedical Engineering, Faculty of Engineering and Information Technology, The University of Melbourne, Melbourne, Victoria 3010, Australia.
⁵ Department of Surgery, University of Melbourne, St Vincent's Hospital Melbourne, Melbourne, Victoria 3065, Australia.
⁶ Centre for Optical Sciences and Department of Health Sciences and Biostatistics, Swinburne University of Technology, Hawthorn, Victoria 3122, Australia.
⁷ Department of Health Sciences and Biostatistics, Swinburne University of Technology, Hawthorn, Victoria 3122, Australia.
⁸ Immune Signalling Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria 3000 Australia.
⁹ Melbourne Medical School, Faculty of Medicine, Dentistry and Health Science, The University of Melbourne, Melbourne, Victoria 3010, Australia.
¹⁰ School of Electrical and Biomedical Engineering, RMIT University, Melbourne, Victoria 3001, Australia.
¹¹ Department of Medicine, University of Melbourne, St Vincent's Hospital Melbourne, Melbourne, Victoria 3065, Australia.
¹² Department of Biochemistry and Chemistry, Biomedical and Environmental Sensor Technology Centre, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia.
¹³ Iverson Health Innovation Research Institute, Swinburne University of Technology, Melbourne, Victoria 3122, Australia.

PMID: 38830774
DOI: 10.1021/acsabm.4c00523

Abstract

Nerve growth factor (NGF) plays a crucial role in cellular growth and neurodifferentiation. To achieve significant neuronal regeneration and repair using in vitro NGF delivery, spatiotemporal control that follows the natural neuronal processes must be developed. Notably, a challenge hindering this is the uncontrolled burst release from the growth factor delivery systems. The rapid depletion of NGF reduces treatment efficacy, leading to poor cellular response. To address this, we developed a highly controllable system using graphene oxygen (GO) and GelMA hydrogels modulated by electrical stimulation. Our system showed superior control over the release kinetics, reducing the burst up 30-fold. We demonstrate that the system is also able to sequester and retain NGF up to 10-times more efficiently than GelMA hydrogels alone. Our controlled release system enabled neurodifferentiation, as revealed by gene expression and immunostaining analysis. The increased retention and reduced burst release from our system show a promising pathway for nerve tissue engineering research toward effective regeneration.

Keywords: GelMA; GelMA/GO; NGF; NGF release; NGF uptake; electrical stimulation; electroactive hydrogels; nerve growth factor.

MeSH terms

Animals
Biocompatible Materials* / chemistry
Biocompatible Materials* / pharmacology
Electric Stimulation*
Graphite* / chemistry
Graphite* / pharmacology
Hydrogels* / chemistry
Hydrogels* / pharmacology
Materials Testing
Nerve Growth Factor* / chemistry
Nerve Growth Factor* / metabolism
Nerve Growth Factor* / pharmacology
Nerve Regeneration* / drug effects
PC12 Cells
Particle Size
Rats
Tissue Engineering

Substances

Hydrogels
Graphite
Nerve Growth Factor
Biocompatible Materials
graphene oxide