Review articleRecent advances in light-induced cell sheet technology
Graphical abstract
Introduction
Generally, the means of regenerative medicine can be categorized into cell-scaffold, cell-based, and scaffold-based techniques [1]. In the initial studies, scaffolds were adopted as supporting devices for seeding cells. Recently, cell sheet technology, an approach for scaffold-free tissue engineering, has become a hot research topic in regenerative medicine due to increased viability and convenient transplantation for various applications [2]. To date, multiple methods have been adopted to fabricate a cell sheet with an intact extracellular matrix (ECM). The most commonly adopted material is thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) with a lower critical solution temperature (LCST, 32°C in aqueous media), below which it is hydrophilic while it is hydrophobic above this temperature. Therefore, PNIPAAm coatings allow for cell sheet detachment below 32°C [3]. Some investigations have applied magnetic forces or electrical potential, although with these two methods, the released cells or cell sheets are likely to contain residual materials from the layer beneath them [4]. A decrease in pH could induce the decomposition of particles precipitated onto a culture dish, thus resulting in the detachment of the cell sheets. However, acidic environments are likely to negatively impact the cell viability [5]. Recently, light-induced cell sheet technology has emerged as a new approach with significant advantages in addition to preserving the ECM [6], [7], [8], [9], [10], [11], [12]. Since no material residue remains on the cell sheets [6] and intercellular interactions and microenvironment are maintained [13], [14], [15], this method is not only noninvasive but also relatively safe for cells at proper wavelengths, power densities, and illumination times, contributing to better outcomes in tissue engineering. Satisfactory cellular viability is guaranteed by this safe technology and can be confirmed by live/dead cell staining, flow cytometry, and cell proliferation assays. Specifically, light illumination is easy to control [7], resulting in convenience and efficiency of manipulation and harvesting.
The light-induced cell sheet harvesting approach was first reported in 2013 [4]. In that study, the detachment of the cell sheet was realized through the application of UV light, inducing a wettability change of titanium dioxide (TiO2). Later, light of various wavelengths and multiple biocompatible material surfaces were found to be efficient and successful in this new method. Due to the rapid advances in light-induced cell sheet technology, there is a great need to summarize the research results of this favourable technology.
This review describes the definition and recent developments of light-induced cell sheet technology and is categorized according to light wavelengths, mechanisms and current applications in tissue engineering. Future perspectives regarding potential materials and means of improving the efficiency are discussed as well.
Section snippets
Survey literature on light-induced cell sheet technology
In this section, we list recent studies in light-induced cell sheet technology according to the kind of light source. The materials, procedures, and results of each study are summarized, while the specific mechanisms are discussed in section 3.
Surface wettability change under light illumination
Wettability is generally measured by the contact angle (CA) of a water droplet deposited on a surface. A CA below 90° is indicative of a hydrophilic surface, while a CA greater than 90° indicates a hydrophobic surface [30]. Various materials, including not only organic material substrates [28] but also TiO2 surfaces [20], have been confirmed to transform from hydrophobic to hydrophilic under light irradiation. After UV treatment, the two-coordinated bridging oxygen sites at the Ti surface can
Applications of light-induced cell sheet technology
As light-induced cell sheet harvesting has emerged only in recent years, until now, there have been few reports on its application in vivo. Herein, the adoption of cell sheets acquired by this method using the three kinds of light sources mentioned above to osseointegration and skin wound healing is introduced (Fig. 5). The satisfying outcomes indicate that in addition to mechanical [41], [42], [43], [44], thermal [45], [46], and other approaches, this new technology holds great potential in in
Challenges and limitations
Despite the satisfying and efficient outcomes, some challenges remain, especially the influence of light illumination on cell viability and cell sheet integrity. The studies mentioned above suggested that upon a short irradiation time, the cell viability was not significantly inhibited by the UV [17] and NIR [15] light, while prolonged irradiation would negatively affect the cell sheet integrity [28] and result in thermal cell killing [12]. Since ROS, the reason for visible light-induced cell
Future perspectives
Since light illumination is a convenient, safe, and rapid means to fabricate cell sheets, more attention should be focused on light-responsive material surfaces suitable for culturing and releasing cell sheets. Therefore, other materials with diverse light-sensitive mechanisms are listed here, providing insight into future research (Table 2).
Conclusion
Recently, tissue regeneration through light-induced cell sheet harvesting has gained much attention. Compared with other stimuli, such as temperature, magnetism, pH, and electricity, light illumination is a noninvasive and rapid method to fabricate a complete and viable cell sheet. Under proper wavelengths, power density, and exposure time, light is safe for cell viability and subsequent cell behaviours. In this paper, several investigations were summarized, which all attempted to acquire cell
Declaration of Competing Interest
The authors confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.
Acknowledgements
This work was supported by the Natural Science Foundation of Zhejiang Province [grant numbers LQ19H140006) and the National Natural Science Foundation of China [grant numbers 81901051]. The authors declare no competing financial interest. We would like to acknowledge AJE editorial team, for medical editing assistance with an earlier version of the manuscript.
References (84)
- et al.
Light-induced cell detachment for cell sheet technology
Biomaterials
(2013) - et al.
Exogenous ROS-induced cell sheet transfer based on hematoporphyrin-polyketone film via a one-step process
Biomaterials
(2018) - et al.
Surface hydroxyls regulation promotes light-induced cell detachment on TiO2 nanodot films
Surf. Coat. Technol.
(2019) - et al.
Effects of RGD immobilization on light-induced cell sheet detachment from TiO2 nanodots films
Mater. Sci. Eng. C. Mater. Biol. Appl.
(2016) - et al.
A facile synthesis of polydopamine/TiO2 composite films for cell sheet harvest application
Colloids. Surf. B. Biointerfaces.
(2018) - et al.
Effective stacking and transplantation of stem cell sheets using exogenous ROS-producing film for accelerated wound healing
Acta. Biomater.
(2019) - et al.
Synthesis of temperature and light sensitive mixed polymer brushes via combination of surface-initiated PET–ATRP and interface-mediated RAFT polymerization for cell sheet application
Appl. Surf. Sci.
(2020) - et al.
Surface hydroxyl groups direct cellular response on amorphous and anatase TiO2 nanodots
Colloids. Surf. B. Biointerfaces.
(2014) - et al.
Curcumin-mediated bone marrow mesenchymal stem cell sheets create a favorable immune microenvironment for adult full-thickness cutaneous wound healing
Stem. Cell. Res. Ther.
(2018) - et al.
Characterization of human ethmoid sinus mucosa derived mesenchymal stem cells (hESMSCs) and the application of hESMSCs cell sheets in bone regeneration
Biomaterials
(2015)
Thermoresponsive polyurethane/siloxane membrane for wound dressing and cell sheet transplantation: in-vitro and in-vivo studies
Mater. Sci. Eng. C. Mater. Biol. Appl.
Blue light exposure in vitro causes toxicity to trigeminal neurons and glia through increased superoxide and hydrogen peroxide generation
Free. Radical. Bio. Med.
Ultraviolet-driven switchable superliquiphobic/superliquiphilic coating for separation of oil-water mixtures and emulsions and water purification
J. Colloid. Interf. Sci.
How did the structural ZnO nanowire as antibacterial coatings control the switchable wettability
Appl. Surf. Sci.
Preparation of reversible photoresponsive poly(SPA-co-MMA) films by electrospinning: a possible route to smart materials for regulating wettability and humidity
Adv. Mater. Technol.
Photo-responsive smart surfaces with controllable cell adhesion
J. Photoch. Photobio. A.
Clinical application status of articular cartilage regeneration techniques: tissue-engineered cartilage brings new hope
Stem. Cells. Int.
Recent advances in ROS-responsive cell sheet techniques for tissue engineering
Int. J. Mol. Sci.
Hepatocyte transplantation: cell sheet technology for liver cell transplantation
Curr. Transplant. Rep.
Detachment of mesenchymal stem cells and their cell sheets using pH-responsive CaCO3 particles
Mater. Trans.
A facile approach to improve light induced cell sheet harvesting through nanostructure optimization
RSC. Adv.
SiO2/TiO2 nanocomposite films on polystyrene for light-induced cell detachment application
ACS. Appl. Mater. Interfaces.
Light-controlled BMSC sheet-implant complexes with improved osteogenesis via an LRP5/beta-catenin/Runx2 regulatory loop
ACS. Appl. Mater. Interfaces.
Cell-sheet-derived ECM coatings and their effects on BMSCs responses
ACS. Appl. Mater. Interfaces.
Gradient photothermal field for precisely directing cell sheet detachment
Adv. Biosyst.
Harvesting of living cell sheets by the dynamic generation of diffractive photothermal pattern on PEDOT
Adv. Funct. Mater.
Visible-light-responsive surfaces for efficient, noninvasive cell sheet harvesting
ACS. Appl. Mater. Interfaces.
Protein-engineered large area adipose-derived stem cell sheets for wound healing
Sci. Rep-Uk.
Physical properties of anatase TiO2 nanocrystallites: based photoanodes doped with Cr2O3
Opt. Quantum. Electron.
Light-induced cell-sheet harvest on TiO2 films sensitized with carbon quantum dots
Chempluschem
TiO/ZnO composite nanodots films and their cellular responses
J. Sol-Gel Sci. Technol
Gr/TiO2 films with light-controlled positive/negative charge for cell harvesting application
Acs. Biomater. Sci. Eng.
The effects of TiO2 nanodot films with RGD immobilization on light-induced cell sheet technology
Biomed. Res. Int.
Laminin-521 promotes rat bone marrow mesenchymal stem cell sheet formation on light-induced cell sheet technology
Biomed. Res. Int.
Improved osseointegrating functionality of cell sheets on anatase TiO2 nanoparticle surfaces
RSC. Adv.
Engineering prevascularized composite cell sheet by light-induced cell sheet technology
RSC. Adv.
Light-induced cell alignment and harvest for anisotropic cell sheet technology
ACS. Appl. Mater. Interfaces.
Photothermally induced local dissociation of collagens for harvesting of cell sheets
Angew. Chem. Int. Ed. Engl.
Reversibly switchable wettability
Chem. Soc. Rev.
Surface hydroxyl groups regulate the osteogenic differentiation of mesenchymal stem cells on titanium and tantalum metals
J. Mater. Chem. B.
Modulation of protein behavior through light responses of TiO2 nanodots films
Sci. Rep-Uk.
Promoting endothelial cell affinity and antithrombogenicity of polytetrafluoroethylene (PTFE) by mussel-inspired modification and RGD/heparin grafting
J. Mater. Chem. B.
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2023, Smart Materials in MedicineCitation Excerpt :Since then a variety of other smart stimuli-responsive materials has been developed and described. Electro-responsive [2], photo-responsive [3], light-induced [4] and pH-sensitive surfaces [5], magnetite nanoparticles coupled with magnetic forces [6], ion-induced polyelectrolyte multilayers [7] are all used for non-enzymatic cell sheet detachment. These and other detachment options are discussed in detail in a number of recent reviews [4,8–11].
Nanomaterial-based cell sheet technology for regenerative medicine and tissue engineering
2022, Colloids and Surfaces B: BiointerfacesCitation Excerpt :The total energy for cell sheet detachment reached 3360 mJ/cm2, less than half of the safe value (7500 mJ/cm2) [60]. The mechanism by which TiO2 nanodot detaches the cell sheet was determined to be the change in wettability and electron accumulation [61]. Commonly, we measure the wettability by determining the contact angle (CA) of a water droplet.
Photo- and thermo-responsive extracellular matrix mimicking nano-coatings prepared from poly(N-isopropylacrylamide)-spiropyran copolymer for effective cell sheet harvesting
2022, Progress in Organic CoatingsCitation Excerpt :However, cell attachment and detachment stay intact, implying that the alterations in surface properties as a result of photo-isomerization of low molecular weight compounds of SP cannot correctly control the adsorption of membrane proteins and ECM [41]. Consequently, in order to induce dynamic movement on a surface to prepare a soft interface for controlling cellular behavior, copolymerization of SP with other monomers and immobilizing them on the surface through various technics such as electron beam (EB) radiation, grafting-to and grafting-from is considered to be a promising strategy to provide photo-responsive cell culture plate [42,43]. EB as a primary method for coating PNIPAAm [44] is prone to some disadvantages such as non-uniformity, high-price, unavailability and difficulty in controlling on the polymer structure.
Spiropyran-based advanced photoswitchable materials: A fascinating pathway to the future stimuli-responsive devices
2022, Journal of Photochemistry and Photobiology C: Photochemistry ReviewsCitation Excerpt :It has been reported that the remote control triggers are more desirable with respect to the conventional cell detaching agents such as trypsin and EDTA for harvesting cell sheets [415–418]. Cell sheets are constructed by grafting thermo-responsive polymers onto the dishes and this would supply cells to adhere, proliferate and spontaneously detach via temperature change in the range of 37–32 °C without any proteolytic enzymes [419]. However, spatial control in single cells via thermal stimulation is not possible and reaching to thermal equilibrium in thermo-responsive polymer is not rapid [420–423].
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These authors contributed equally.