Periodic Reporting for period 1 - ELECTROSKIN (Piezoelectric Nanogenerators for skin wound healing)
Période du rapport: 2020-04-01 au 2022-03-31
ELECTROSKIN is an interdisciplinary project that explore new strategies based on energy harvesting and energy transformation tools aimed at improving skin wound healing. The project joins two different research fields, electronic engineering and tissue regeneration, and two research groups from different countries of the European Union.
Electrical stimulation has demonstrated to be beneficial to treat and regenerate various tissues. In epithelium of healthy skin, a constant electric potential is maintained. When skin layers are damaged, their electric resistance disappears and results in electric field created locally in the injured epithelium. However, endogenous electric fields are compromised or absent in chronic wounds. Diabetic skin and normal skin of old patients had lower transepithelial potential and reduced electrical currents in wounded skin, in connection with the delay in impaired microcirculation. Chronic wounds include pressure ulcers, venous leg ulcers, arterial ulcers, neurotrophic ulcers, and foot ulcers in people with diabetes. It is estimated that 1-2% of the population will experience a chronic wound during their lifetime. Moreover, it is considered that the number of patients suffering from non-healing wounds is reaching epidemic proportions. In nationals’ healthcare systems, chronic wounds impose an immense financial burden, as well as productivity. It is therefore necessary to continue working on new therapeutic strategies to improve wound healing.
The use of exogenous electric fields to enhance wound healing is an interesting approach. However, the way how to apply the electric fields is under study. The use of traditional electrodes to create electric fields has the disadvantages of low spatial resolution and the need for external electrical sources. In ELECTROSKIN project, we propose the use of piezoelectric nanogenerators, which create an inherent electric field when they are strained, to treat chronic wounds. The local electric field created at the interest site is produced without the need for external power and electrodes. To achieve this general purpose, we defined specific objectives. The first step has been to determine the safety of the new piezoelectric nanogenerators fabricated. Then, to better understand the effect of piezoelectric nanogenerators on skin tissue, we proposed the development of an in vitro 3D skin construct that intend to mimic the in vivo conditions. The 3D skin construct would allow the integration of the nanogenerators and be a model for the study of other materials for skin regeneration. Finally, the effect of electric fields generated by the nanogenerators on skin cells have been analysed using cell culture characterization that include gene expression and protein synthesis.
Electrical stimulation has demonstrated to be beneficial to treat and regenerate various tissues. In epithelium of healthy skin, a constant electric potential is maintained. When skin layers are damaged, their electric resistance disappears and results in electric field created locally in the injured epithelium. However, endogenous electric fields are compromised or absent in chronic wounds. Diabetic skin and normal skin of old patients had lower transepithelial potential and reduced electrical currents in wounded skin, in connection with the delay in impaired microcirculation. Chronic wounds include pressure ulcers, venous leg ulcers, arterial ulcers, neurotrophic ulcers, and foot ulcers in people with diabetes. It is estimated that 1-2% of the population will experience a chronic wound during their lifetime. Moreover, it is considered that the number of patients suffering from non-healing wounds is reaching epidemic proportions. In nationals’ healthcare systems, chronic wounds impose an immense financial burden, as well as productivity. It is therefore necessary to continue working on new therapeutic strategies to improve wound healing.
The use of exogenous electric fields to enhance wound healing is an interesting approach. However, the way how to apply the electric fields is under study. The use of traditional electrodes to create electric fields has the disadvantages of low spatial resolution and the need for external electrical sources. In ELECTROSKIN project, we propose the use of piezoelectric nanogenerators, which create an inherent electric field when they are strained, to treat chronic wounds. The local electric field created at the interest site is produced without the need for external power and electrodes. To achieve this general purpose, we defined specific objectives. The first step has been to determine the safety of the new piezoelectric nanogenerators fabricated. Then, to better understand the effect of piezoelectric nanogenerators on skin tissue, we proposed the development of an in vitro 3D skin construct that intend to mimic the in vivo conditions. The 3D skin construct would allow the integration of the nanogenerators and be a model for the study of other materials for skin regeneration. Finally, the effect of electric fields generated by the nanogenerators on skin cells have been analysed using cell culture characterization that include gene expression and protein synthesis.
Work was conducted via 7 work packages (WPs). WP1 was planned for the characterization of the nanogenerators biocompatibility on skin cells. The newly developed ZnO nanosheets arrays and PVDF nanofibrous membranes demonstrated to be biocompatible without any harmful effect on cells. This first WP was crucial for the progress of the project. In parallel, a combined PVDF membrane coated with ZnO nanosheets was fabricated and optimized for cell culture applications. WP2 was to create an in vitro 3D skin construct for the analysis of the piezoelectric nanogenerators effect and other biomaterials. We obtained an interesting model of skin tissue based on collagen and with the presence of keratinocytes, endothelial cells and adipose-derived stem cells. The skin construct allowed to integrate any type of membrane or porous material, so can be used for several research group. This WPs was considered a key one and includes several of the most important tasks of the project. In WP3 and WP4, we analyzed the effect of local electric fields on skin cell types. Interestingly, the forces generated by the cells were enough to create local electric fields that enhanced the differentiation of keratinocytes and fibroblasts. In addition, the gene expression pattern changed due to the electric fields generated. In WP5, we were able to characterize the nanogenerator and we estimated the piezopotential that ZnO nanosheets produced when cells apply a force using finite element modeling. Finally, WP6 and WP7 were focused on the dissemination and exploitation of the results and the research and financial management.
Results of the ELECTROSKIN project were communicated in four international conferences. The experienced researcher has attended and presented the results at the 11th World Biomaterials Congress, the European Society for Biomaterials Conference 2021 and the Nanocon 2021, all of them in the field of biomaterials and nanotechnology. In addition, a PhD of the experienced researcher has presented the results at the MEMS 2021 conference. Moreover, part of the results derived from the project have been published in Nanomaterials journal, an international open-access journal. Two forthcoming manuscripts are being prepared about the development of the in vitro 3D skin construct and the effect of nanogenerators on skin cells. The intellectual property generated during the project is now at a preparation stage to be protected as a utility model.
The management of the project was done by the experienced researcher together with the management department and the supervisors. The ELESTROSKIN project has allowed the researcher to lead his own project and coordinate an interdisciplinary group. He has collaborated with two international laboratories and two national ones. In addition, he has learned important skills in management and scientific methods about skin tissue engineering research. Finally, all the experience acquired has paved the way to obtain the postdoctoral grant Beatriu de Pinós funded by the Government of Catalonia in collaboration with COFUND programme to attract post-doctoral research talent.
Results of the ELECTROSKIN project were communicated in four international conferences. The experienced researcher has attended and presented the results at the 11th World Biomaterials Congress, the European Society for Biomaterials Conference 2021 and the Nanocon 2021, all of them in the field of biomaterials and nanotechnology. In addition, a PhD of the experienced researcher has presented the results at the MEMS 2021 conference. Moreover, part of the results derived from the project have been published in Nanomaterials journal, an international open-access journal. Two forthcoming manuscripts are being prepared about the development of the in vitro 3D skin construct and the effect of nanogenerators on skin cells. The intellectual property generated during the project is now at a preparation stage to be protected as a utility model.
The management of the project was done by the experienced researcher together with the management department and the supervisors. The ELESTROSKIN project has allowed the researcher to lead his own project and coordinate an interdisciplinary group. He has collaborated with two international laboratories and two national ones. In addition, he has learned important skills in management and scientific methods about skin tissue engineering research. Finally, all the experience acquired has paved the way to obtain the postdoctoral grant Beatriu de Pinós funded by the Government of Catalonia in collaboration with COFUND programme to attract post-doctoral research talent.
ELECTROSKIN project is having an important impact in the two research fields, electronic engineering and tissue regeneration. The development and optimization of new nanogenerators for their use in biomedical applications is necessary when a new strategy for wound healing is proposed. The nanogenerators have a great interest in skin tissue regeneration, but also in other healthcare applications where the electric fields are involved, such as neural disorders, bone regeneration, muscle activation and others. In the regard of wound healing, chronic wounds are the target due to the reduction of the endogenous electric fields. The present project was initial research, so it was not planned to achieve in vivo or clinical stage. However, the results allow to reaffirm the great potential of nanogenerators to enhance skin regeneration. The knowledge generated through the implementation of the project is an important step in skin wound healing. We have opened the door to an alternative strategy to address the healing of chronic wounds. Indeed, through ELECTROSKIN, valuable feedback between electronics and skin tissue engineering has been emerged and the scientific knowledge generated will stimulate the interdisciplinary thinking to address the future medical issues.