Organic piezoelectrics
1. Background and state-of-the-art
Organic piezoelectrics, capable to “sense” delicate forces in living organism and transfer them into effective electrical signal equivalent to the signals used by organism itself for self-regeneration, hold a promising potential for many regenerative problems currently without any solution.1 Electro-stimulated regeneration, as clinically accepted regeneration technique, has been used for repairing peripheral nerve injuries for a long period of time.2 Human body generates biological electrical fields (EFs) (endogenous EF (500 mV/mm) and transmembrane potentials (-10 to -90 mV)), which are responsible for natural electro-stimulated regeneration.3 It has been clearly evidenced that stimulating wound with external electrical patches promotes healing.5 This point is particularly important for the future of tissue engineering. Mimicking biophysical processes which naturally occur during self-repair of wounds and damaged tissues inside living organism provides a lot of possibilities for designing next generation of medical devices with regeneration-stimulating capacity.4 They will minimize application of biochemical stimuli (like immune-modulating drugs, antibiotics and growth factors) which are usually prescribed during post-implantation regeneration and can be a source of numerous adverse reactions. Strong future efforts should be put in investigations of the basic phenomena which take place at the interface between stimulating materials and stimulated cells.5 This might open new avenues for future applications in regeneration, drug delivery, bioelectronics, precise surgery and microrobotics.
Figure 1: Perspectives of organic piezoelectrics in biomedicine: examples of implantable and non-implantable, transcutaneous electrostimulators used today and their general properties; voltage- and mechano- sensitive protein channels in human cell membranes potentially affected during stimulation 6 and the question of actin filaments role in this process; example of the future organic piezostimulator and its properties as well as predictions of its potential applications.
2. Objectives, originality and impact on new research approaches
The main objective of proposed research is to design next generation of implantable/self-removing piezoelectric electrostimulators able to sense, detect and control electrostimulation at cellular level. For that purpose we aim:
- NEW ORGANIC PIEZOELECTRICS: Designing novel organic piezoelectrics with nanotextured and hydrophilic surface, characterized by biodegradability and biocompatibility (based on PLLA structures with or without integrated fillers).
- NEW PROCESSING APPROACHES: Application and optimization of different processing approaches (including uniaxial drawing, template-assisted structuring, electrospinning, solution blow spinning, electrowriting, electrospraying, 3D (bio)printing) for tailoring properties of organic piezoelectrics.
- NEW TOOLS FOR INTERACTIONS WITH CELLS: Constructing novel piezoelectric device able to detect, heal and self-remove and exploring piezostimulation at cellular level by visualizing mechanical deformation and generated voltage.
Figure 2: Organic piezoelectrics in our lab: organic piezostructures developed in our lab using different processing approaches; human cells on the surface of organic piezoelectrics; and future goal toward designing personalized organic piezo-stimulator.
So far we have designed piezoelectric PLLA in different morphological forms, including drawn films, oriented nano-tubes, fibers and 3D structures (illustrated in Fig. 2).7-9 We have optimized highly efficient protocol for modified their surface to be hydrophilic.7 In our research, we investigated biodegradability of the PLLA and correlated piezoelectric properties of the polymer with enzyme-assisted biodegradation.9 Recently, we have shown that small fraction (1wt%) of filler, characterized by morphological anisotropy, significantly affects crystallization and orientation of the polymer thereby contributing to the increase of its piezoelectricity.10 We found that cells adhered to these type of piezo-PLLA structures follow the drawing direction of the polymer which matches with orientation of dipoles.10
3. Unique methodology
Novel method will be developed to incorporate voltage- and mechano- sensitive dyes into PLLA matrix. One of the approaches will include plasma-mediated surface group modifications that will enable covalent bonding between dyes and polymer functional groups. In addition to melting-assisted stretching, we will work on processing piezo-PLLA layers using epitaxial growth as well as 3D printing.
Figure 3: Ultrasound-activated piezo-PLLA and corresponding activation of actin filaments in human skin cells.10
REFERENCES
1 S. Guerin, et al, NPG Asia Materials, 11, 10, 2019.
2 Brian A Karamian, et al, J Orthop Traumatol. 23, 2, 2022.
3 Meng, S., Rouabhia, M. & Zhang, Z. Applied Biomedical Engineering, 37–62, 2011.
4 R. Luo et al, Adv. Healthcare Mater. 2021, 10, 2100557.
5 S.Zhao et al, Cell Mol Life Sci. 2020 Jan 23;77(14):2681–2699.
6 Murthy, S. E., Dubin, A. E. & Patapoutian, A. Nat. Rev. Mol. Cell Biol., 2017. 18, 771–783, 2017.
7 L. Udovc, M. Spreitzer, M. Vukomanovic, Polymer Journal, 52, 299–311, 2020. https://doi.org/10.1038/s41428-019-0281-5
8 L. Gazvoda, M. Perisic-Nanut, M. Spreitzer, M. Vukomanovic, Biomater. Sci., 10, 4933-4948, 2022. https://doi.org/10.1039/D2BM00644H
9 L. Gazvoda, B. Visic, M. Spreitzer, M. Vukomanovic, Polymers, 13(11), 1719, 2021. https://doi.org/10.3390/polym13111719
10 M. Vukomanović, L. Gazvoda, M. Kurtjak, M. Maček-Kržmanc, M. Spreitzer, Q. Tang, J. Wu, H. Ye, X. Chen, M. Mattera, J. Puigmartí-Luis, S. Vidal Pane, Small, 19, 2301981, 2023. https://doi.org/10.1002/smll.202301981
Biomaterials team
Team Leader: Dr. Marija Vukomanović
Researchers: Dr. Lea Gazvoda
Young Researchers: Martina Žabčić
Figure 4. Biomaterials team: working on designing advanced biomaterials.