Bioengineered Skin Intended for Skin Disease Modeling
Abstract
:1. General Considerations
1.1. Skin
1.2. Bioengineered Skin
1.3. Applications of Bioengineered Skin
2. Skin Disease Models and Their Fabrication
2.1. Skin Disease Models
2.1.1. Monolayer Models
2.1.2. Reconstructed Human Epidermis (RHS)
2.1.3. De-Epidermalized Dermis (DED)
2.1.4. Collagen Hydrogels
2.1.5. Self-Assembled Models
2.1.6. Skin-on-Chip Models
2.2. Fabrication Methods
2.2.1. Manual Fabrication Methods
2.2.2. Automated Fabrication Methods
- Laser-assisted bioprinting exploits laser energy for the printing. Small droplets of cells are printed on a substrate that can be either a cell culture plate for generation of 2D construct or a scaffold for formation of 3D construct. Precise deposition of the cells in the 3D construct in a high density is achieved by this method while there are no limitations in biomaterials viscosity. Several dermo-epidermal skin substitutes have been already successful fabricated by this method [2,20]. A downside of laser-assisted bioprinting is the relatively low printing speed [2].
- Inkjet bioprinting is based on the ejection of bio-ink droplets on a substrate. Bio-ink contains cell suspension combined with hydrogels or biopolymers. In thermal inkjet bioprinting the droplets are pushed out due to bubbles generated in the nozzle by a heating element, while in piezoelectric inkjet bioprinting, electric pulses result in the droplets ejection [2,34]. Thermal inkjet printing is considered suitable for biological applications as the printed cells are heated at a temperature of less than 10 °C above ambient temperature and for only 2 microseconds, ensuring cell survival during the printing and a later cell viability of about 90%, while piezoelectric approach operates at frequencies that can harm the cells [34]. Inkjet bioprinting can achieve high resolutions and accuracy in deposition but it is efficient only when bio-inks of low viscosity are printed [2]. It has been used for the printing of keratinocytes on top of a previously extrusion-based printed dermal equivalent and it resulted in a very uniform epidermal layer in which keratinocytes quickly and properly proliferated and differentiated throughout the cultivation period [40].
- Extrusion bioprinting is based on the extrusion of a continuous strand of biopolymers or hydrogels, along with cellular components when desired, through a nozzle when mechanical force is applied. Simultaneous printing of cells, biomaterials and growth factors can be achieved in systems of more than one extruder, contributing to the generation of a more complex skin model. This approach is not considered faster than inkjet and laser-assisted bioprinting, but it is suitable for generation of anatomically relevant structures and sizes [2,37]. It also works with high cell density although shear stresses developed in the nozzle may reduce cell viability. Comparison between 3D extrusion bioprinting and manual deposition of skin components revealed the better long-term maintenance of skin equivalents shape and size in case of 3D printing approach [2]. Due to all these advantages, this method could be employed for the generation of dermis which ideally consists not only of fibroblasts and the dermal matrix, but also of several molecular and cellular components. For example, Byoung Soo Kim et al. used this method to fabricate collagen-based scaffolds, including or not polycaprolactone, to form the dermal component of a skin substitute, the epidermal layer of which was later created by inkjet-printing of keratinocytes, as mentioned above [40]. However, this method shorts on resolution capabilities compared to other bioprinting techniques, which affects the precision in cell spatial arrangement [41].
3. Skin Disease Modeling and Drug Screening
3.1. Modeling of Physiological Conditions
3.2. Modeling of Pathological Conditions
3.3. Evaluation of Compounds Safety and Efficacy
4. Discussion
5. Conclusions
Funding
Conflicts of Interest
References
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Skin Model | Cells | Matrix | Advantages | Disadvantages |
---|---|---|---|---|
Monolayer models | Keratinocytes or fibroblasts | - | Differentiated epidermis | 2D environment, no cellular interactions |
Reconstructed human epidermis | Keratinocytes | Polycarbonate | Differentiated epidermis, 3D environment | No cellular interactions |
De-epidermalized dermis | Fibroblasts or fully acellular | Natural ECM | 3D environment, dermo-epidermal equivalent after keratinocytes seeding | Keratinocytes absence, limited availability |
Collagen hydrogels | Fibroblasts (embedded in collagen hydrogels), keratinocytes (seeded on top of hydrogel) | Collagen I (can be combined with GAGs, chitosan or other collagen types) | 3D environment, dermo-epidermal equivalent, availability, easy production | No native ECM, contraction of hydrogels |
Self-assembled models | Fibroblasts (embedded in collagen hydrogels), keratinocytes (seeded on top of hydrogel) | Natural ECM | 3D environment, dermo-epidermal equivalent, fully autologous skin model | Slow and tedious process |
Skin-on-chip models | Fibroblasts, keratinocytes, endothelial cells, other organs’ cell types | Porous membranes, scaffolds, or other | 3D environment, interactions between different cell types or organs | Complex systems, no native ECM |
Fabrication Method | Potentials | Limitations |
---|---|---|
Manual fabrication | Incorporation of several cells/molecules, personalization opportunities, fast adaptation to research needs | Slow and tedious process, non-standardized method |
Fabrication by robots | Incorporation of several cells/molecules, personalization opportunities, standardized production | Slow process, high-complexity and decreased adaptability |
3D bioprinting | Incorporation of several cells/molecules, personalization opportunities, standardized production, faster process | High-complexity and decreased adaptability, expensive |
Automated injection molding | Personalization opportunities, standardized production, non-complex process, faster than manual or robotic production | Still slow process, validated only for dermis fabrication yet |
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Sarkiri, M.; Fox, S.C.; Fratila-Apachitei, L.E.; Zadpoor, A.A. Bioengineered Skin Intended for Skin Disease Modeling. Int. J. Mol. Sci. 2019, 20, 1407. https://doi.org/10.3390/ijms20061407
Sarkiri M, Fox SC, Fratila-Apachitei LE, Zadpoor AA. Bioengineered Skin Intended for Skin Disease Modeling. International Journal of Molecular Sciences. 2019; 20(6):1407. https://doi.org/10.3390/ijms20061407
Chicago/Turabian StyleSarkiri, Maria, Stephan C. Fox, Lidy E. Fratila-Apachitei, and Amir A. Zadpoor. 2019. "Bioengineered Skin Intended for Skin Disease Modeling" International Journal of Molecular Sciences 20, no. 6: 1407. https://doi.org/10.3390/ijms20061407