Polímeros: Ciência e Tecnologia
Polímeros: Ciência e Tecnologia
Original Article

Tuning the structure and properties of cell-embedded gelatin hydrogels for tumor organoids

Sarah Oliveira Lamas de Souza; Sérgio Mendes de Oliveira; Catarina Paschoalini Lehman; Mercês Coelho da Silva; Luciana Maria Silva; Rodrigo Lambert Oréfice

Downloads: 1
Views: 425


Tumor organoids have great potential as a 3D in vitro system to model cancer. In this work, we studied how the structure of hydrogels based on gelatin with methacryloyl groups (GeIMA) can affect their usage in tumor organoids. To this end, gelatin hydrogels with different levels of methacrylation and with cellulose nanocrystals (NCC) or reduced graphene oxide (rGO) were prepared and used to encapsulate human colon carcinoma cells (RKO). Mechanical properties of the hydrogels were measured in dynamic conditions at 37°C and water. Results showed that NCC was able to provide higher mechanical stability to the hydrogels. RKO cells embedded in GelMA were able to proliferate within the hydrogels, leading to the formation of groups of cells after 48 h. GelMA with higher crosslink densities and NCC tended to show higher cell population as possibly due to the higher level of stability and rigidity displayed by these hydrogels.




gelatin methacryloyl, GeIMA, hydrogels, organoid, three-dimensional cell culture


1 Aamodt, J. M., & Grainger, D. W. (2016). Extracellular matrix-based biomaterial scaffolds and the host response. Biomaterials, 86, 68-82. http://dx.doi.org/10.1016/j.biomaterials.2016.02.003. PMid:26890039.

2 Nuciforo, S., Fofana, I., Matter, M. S., Blumer, T., Calabrese, D., Boldanova, T., Piscuoglio, S., Wieland, S., Ringnalda, F., Schwank, G., Terracciano, L. M., Ng, C. K. Y., & Heim, M. H. (2018). Organoid models of human liver cancers derived from tumor needle biopsies. Cell Reports, 24(5), 1363-1376. http://dx.doi.org/10.1016/j.celrep.2018.07.001. PMid:30067989.

3 Lancaster, M. A., & Knoblich, J. A. (2014). Generation of cerebral organoids from human pluripotent stem cells. Nature Protocols, 9(10), 2329-2340. http://dx.doi.org/10.1038/nprot.2014.158. PMid:25188634.

4 Maenhoudt, N., Defraye, C., Boretto, M., Jan, Z., Heremans, R., Boeckx, B., Hermans, F., Arijs, I., Cox, B., Van Nieuwenhuysen, E., Vergote, I., Van Rompuy, A.-S., Lambrechts, D., Timmerman, D., & Vankelecom, H. (2020). Developing organoids from ovarian cancer as experimental and preclinical models. Stem Cell Reports, 14(4), 717-729. http://dx.doi.org/10.1016/j.stemcr.2020.03.004. PMid:32243841.

5 Thakuri, P. S., Liu, C., Luker, G. D., & Tavana, H. (2018). Biomaterials-based approaches to tumor spheroid and organoid modeling. Advanced Healthcare Materials, 7(6), e1700980. http://dx.doi.org/10.1002/adhm.201700980. PMid:29205942.

6 Lima, F., Melo, W. G., Braga, M. F., Vieira, E., Câmara, J. V., Pierote, J. J., Argôlo, N., No., Silva, E., Fo., & Fialho, A. C. (2021). Chitosan-based hydrogel for treatment of temporomandibular joint arthritis. Polímeros: Ciência e Tecnologia, 31(2), e2021019. http://dx.doi.org/10.1590/0104-1428.20210026.

7 Huang, J., Jiang, Y., Ren, Y., Liu, Y., Wu, X., Li, Z., & Ren, J. (2020). Biomaterials and biosensors in intestinal organoid culture, a progress review. Journal of Biomedical Materials Research. Part A, 108(7), 1501-1508. http://dx.doi.org/10.1002/jbm.a.36921. PMid:32170907.

8 Dong, Z., Yuan, Q., Huang, K., Xu, W., Liu, G., & Gu, Z. (2019). Gelatin methacryloyl (Gelma)-based biomaterials for bone regeneration. RSC Advances, 9(31), 17737-17744. http://dx.doi.org/10.1039/C9RA02695A. PMid:35520570.

9 Soares, G. O. N., Lima, F. A., Goulart, G. A. C., & Oréfice, R. L. (2021). Physicochemical characterization of the gelatin/polycaprolactone nanofibers loaded with diclofenac potassium for topical use aiming potential anti-inflammatory action. International Journal of Polymeric Materials, 71(17), 1303-1318. http://dx.doi.org/10.1080/00914037.2021.1962875.

10 Sun, M., Sun, X., Wang, Z., Guo, S., Yu, G., & Yang, H. (2018). Synthesis and properties of gelatin methacryloyl (Gelma) hydrogels and their recent applications in load-bearing tissue. Polymers, 10(11), 1290. http://dx.doi.org/10.3390/polym10111290. PMid:30961215.

11 Zhu, M., Wang, Y., Ferracci, G., Zheng, J., Cho, N.-J., & Lee, B. H. (2019). Gelatin methacryloyl and its hydrogels with an exceptional degree of controllability and batch-to-batch consistency. Scientific Reports, 9(1), 6863. http://dx.doi.org/10.1038/s41598-019-42186-x. PMid:31053756.

12 Krishnamoorthy, S., Noorani, B., & Xu, C. (2019). Effects of encapsulated cells on the physical-mechanical properties and microstructure of gelatin methacrylate hydrogels. International Journal of Molecular Sciences, 20(20), 5061. http://dx.doi.org/10.3390/ijms20205061. PMid:31614713.

13 Kong, J., & Yu, S. (2007). Fourier transform infrared spectroscopic analysis of protein secondary structures. Acta Biochimica et Biophysica Sinica, 39(8), 549-559. http://dx.doi.org/10.1111/j.1745-7270.2007.00320.x. PMid:17687489.

14 Mertz, G., Fouquet, T., Becker, C., Ziarelli, F., & Ruch, D. (2014). A methacrylic anhydride difunctional precursor to produce a hydrolysis-sensitive coating by aerosol-assisted atmospheric plasma process: hydrolysis-sensitive coating deposited by aerosol assisted atmospheric plasma. Plasma Processes and Polymers, 11(8), 728-733. http://dx.doi.org/10.1002/ppap.201400050.

15 Edmondson, R., Broglie, J. J., Adcock, A. F., & Yang, L. (2014). Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors. Assay and Drug Development Technologies, 12(4), 207-218. http://dx.doi.org/10.1089/adt.2014.573. PMid:24831787.

16 Grenier, J., Duval, H., Barou, F., Lv, P., David, B., & Letourneur, D. (2019). Mechanisms of pore formation in hydrogel scaffolds textured by freeze-drying. Acta Biomaterialia, 94, 195-203. http://dx.doi.org/10.1016/j.actbio.2019.05.070. PMid:31154055.

17 Nichol, J. W., Koshy, S. T., Bae, H., Hwang, C. M., Yamanlar, S., & Khademhosseini, A. (2010). Cell-laden microengineered gelatin methacrylate hydrogels. Biomaterials, 31(21), 5536-5544. http://dx.doi.org/10.1016/j.biomaterials.2010.03.064. PMid:20417964.

18 Achterberg, V. F., Buscemi, L., Diekmann, H., Smith-Clerc, J., Schwengler, H., Meister, J.-J., Wenck, H., Gallinat, S., & Hinz, B. (2014). The nano-scale mechanical properties of the extracellular matrix regulate dermal fibroblast function. The Journal of Investigative Dermatology, 134(7), 1862-1872. http://dx.doi.org/10.1038/jid.2014.90. PMid:24670384.

19 Yue, K., Trujillo-de-Santiago, G., Alvarez, M. M., Tamayol, A., Annabi, N., & Khademhosseini, A. (2015). Synthesis, properties, and biomedical applications of gelatin methacryloyl (Gelma) hydrogels. Biomaterials, 73, 254-271. http://dx.doi.org/10.1016/j.biomaterials.2015.08.045. PMid:26414409.

20 Magno, V., Meinhardt, A., & Werner, C. (2020). Polymer hydrogels to guide organotypic and organoid cultures. Advanced Functional Materials, 30(48), 2000097. http://dx.doi.org/10.1002/adfm.202000097.

64f722a1a95395520b0fc432 polimeros Articles
Links & Downloads

Polímeros: Ciência e Tecnologia

Share this page
Page Sections