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Assessing the Proliferative Impact of Alginate-Gelatin Composites on Mesenchymal Stromal Cells

Yıl 2025, Cilt: 15 Sayı: 1, 119 - 132, 15.03.2025
https://doi.org/10.31466/kfbd.1496088

Öz

Traditional conducted on flat two-dimensional (2D) culture do not closely mirror the physiological and pathophysiological features of the in vivo environment including cell migration, soluble factor gradient and cell-matrix interactions. Three-dimensional (3D) cell culture overcomes these drawbacks by using 3D biomaterials, such as alginate hydrogels, to promote cell migration, vary biomaterial stiffness or permit cell-matrix interactions. In this study, it was aimed to propose a novel 3D platform including alginate-gelatin composites to address the need for tissue engineering techniques that support mesenchymal stromal cell viability and differentiation potential. In the first part, the absorbance spectra of different hydrogel-based biomaterials were examined using UV-visible light. After finding the best performing hydrogel, the work focused on cell proliferation using XTT viability assay and Live/Dead cytotoxicity assay. The cell viability of mesenchymal stromal cells in the best hydrogel biomaterial was compared to other scaffolds including cellulose, alginate-gelatin and only alginate. Alginate-gelatin hydrogel increased MSC viability, in comparison with other scaffolds such as alginate and cellulose. This increase also was significant compared to the cells grown in 2D culture. The findings of this study are consistent with the data of other studies in the literature. Thus, alginate-gelatin composites could be a promising candidate in tissue engineering to improve cell proliferation.

Kaynakça

  • Aggarwal, S., and Pittenger, M. F. (2005). Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood, 105, 1815-1822.
  • Augst, A. D., Kong, H. J., and Mooney, D. J. (2006). Alginate hydrogels as biomaterials. Macromol Biosci, 6, 623-633.
  • Azoidis, I., Metcalfe, J., Reynolds, J., Keeton, S., Hakki, S. S., Sheard, J., and Widera, D. (2017). Three-dimensional cell culture of human mesenchymal stem cells in nanofibrillar cellulose hydrogels. MRS Communications, 7, 458-465.
  • Bhattacharya, M., Malinen, M. M., Lauren, P., Lou, Y-R., Kuisma, S. W., Kanninen, L., Lille, M., Corlu, A., GuGuen-Guillouzo, C., Ikkala, O., Laukkanen, A., Urtti, A., and Yliperttula, M. (2012). Nanofibrillar cellulose hydrogel promotes three-dimensional liver cell culture. Journal of Controlled Release, 164, 291-298.
  • Bowers, S. L., Banerjee, I., and Baudino, T. A. (2010). The extracellular matrix: at the center of it all. J Mol Cell Cardiol, 48, 474-482.
  • Brown, C., McKee, C., Bakshi, S., Walker, K., Hakman, E., Halassy, S., Svinarich, D., Dodds, R., Govind, C. K., and Chaudhry, G. R. (2019). Mesenchymal stem cells: Cell therapy and regeneration potential. J Tissue Eng Regen Med, 13, 1738-1755.
  • Chang, K. A., Lee, J. H., and Suh, Y. H. (2014). Therapeutic potential of human adipose-derived stem cells in neurological disorders. J Pharmacol Sci, 126, 293-301.
  • Chen, W., Pan, W., Wang, J., Cheng, L., Wang, J., Song, L., Hu, Y., and Ma, X. (2022). Emerging two-dimensional monoelemental materials (Xenes): Fabrication, modification, and applications thereof in the field of bioimaging as nanocarriers. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 14, e1750.
  • Daemi, H., and Barikani, M. (2012). Synthesis and characterization of calcium alginate nanoparticles, sodium homopolymannuronate salt and its calcium nanoparticles. Scientia Iranica, 19, 2023-2028.
  • Dimitriou, R., Jones, E., McGonagle, D., and Giannoudis, P. V. (2011). Bone regeneration: current concepts and future directions. BMC Med, 9, 66.
  • Dominici, M., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F. C., Krause, D. S., Deans, R. J., Keating, A., Prockop, D. J., and Horwitz, E. M. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 8, 315-317.
  • Draget, K. I., Skjåk-Bræk, G., and Stokke, B. T. (2006). Similarities and differences between alginic acid gels and ionically crosslinked alginate gels. Food Hydrocolloids, 20, 170-175.
  • Dranseikiene, D., Schrüfer, S., Schubert, D. W., Reakasame, S., and Boccaccini, A. R. (2020). Cell-laden alginate dialdehyde-gelatin hydrogels formed in 3D printed sacrificial gel. J Mater Sci Mater Med, 31, 31.
  • Dutta, R. C., and Dutta, A. K. (2009). Cell-interactive 3D-scaffold; advances and applications. Biotechnol Adv, 27, 334-339.
  • Finkemeier, C. G. (2002). Bone-grafting and bone-graft substitutes. The Journal of bone and joint surgery American volume, 84-a, 454-464.
  • Gugliandolo, A., Fonticoli, L., Trubiani, O., Rajan, T. S., Marconi G. D., Bramanti, P., Mazzon, E., Pizzicannella, J., and Diomede, F. (2021). Oral Bone Tissue Regeneration: Mesenchymal Stem Cells, Secretome, and Biomaterials. International journal of molecular sciences, 22, 5236.
  • Habibovic, P., and de Groot, K. (2007). Osteoinductive biomaterials--properties and relevance in bone repair. J Tissue Eng Regen Med, 1, 25-32.
  • Ho, T-C., Chang, C-C., Chan,, H-P., Chung, T-W., Shu, C-W., Chuang, K-P., Duh, T-H., Yang, M-H., and Tyan, Y-C. (2022). Hydrogels: Properties and Applications in Biomedicine. Molecules, 27, 2902.
  • Jose, G., Shalumon, K. T., and Chen, J-P. (2020). Natural Polymers Based Hydrogels for Cell Culture Applications. Current Medicinal Chemistry, 27, 2734-2776.
  • Kapałczyńska, M., Kolenda, T., Przybyła, W., Zajączkowska, M., Teresiak, A., Filas, V., Ibbs, M., Bliźniak, R., Łuczewski, Ł., and Lamperska, K. (2018). 2D and 3D cell cultures - a comparison of different types of cancer cell cultures. Arch Med Sci, 14, 910-919.
  • Kolk, A., Handschel, J., Drescher, W., Rothamel, D., Kloss, F., Blessmann, M., Heiland, M., Wolff, K-D., and Smeets, R. (2012). Current trends and future perspectives of bone substitute materials – From space holders to innovative biomaterials. Journal of Cranio-Maxillofacial Surgery, 40, 706-718.
  • Kuo, C. K., and Ma, P. X. (2001). Ionically crosslinked alginate hydrogels as scaffolds for tissue engineering: Part 1. Structure, gelation rate and mechanical properties. Biomaterials, 22, 511-521.
  • Liu, K., Wiendels, M., Yuan, H., Ruan, C., and Kouwer, P. H. J. (2022). Cell-matrix reciprocity in 3D culture models with nonlinear elasticity. Bioact Mater, 9, 316-331.
  • McKee, C., and Chaudhry, G. R. (2017). Advances and challenges in stem cell culture. Colloids Surf B Biointerfaces, 159, 62-77.
  • Neves, M. I., Moroni, L., and Barrias, C. C. (2020). Modulating Alginate Hydrogels for Improved Biological Performance as Cellular 3D Microenvironments. Front Bioeng Biotechnol, 8, 665.
  • Park, Y., Huh, K. M., and Kang, S. W. (2021). Applications of Biomaterials in 3D Cell Culture and Contributions of 3D Cell Culture to Drug Development and Basic Biomedical Research. International journal of molecular sciences, 22:
  • Sarker, B., Singh, R., Silva, R., Roether, J. A., Kaschta, J., Detsch, R., Schubert, D. W., Cicha, I., and Boccaccini, A. R. (2014). Evaluation of fibroblasts adhesion and proliferation on alginate-gelatin crosslinked hydrogel. PLoS One, 9, e107952.
  • Sarker, M., Izadifar, M., Schreyer, D., and Chen, X. (2018). Influence of ionic crosslinkers (Ca(2+)/Ba(2+)/Zn(2+)) on the mechanical and biological properties of 3D Bioplotted Hydrogel Scaffolds. J Biomater Sci Polym Ed, 29, 1126-1154.
  • Sheard, J. J., Bicer, M., Meng, Y., Frigo, A., Aguilar, R. M., Vallance, T. M., Iandolo, D., and Widera, D. (2019). Optically Transparent Anionic Nanofibrillar Cellulose Is Cytocompatible with Human Adipose Tissue-Derived Stem Cells and Allows Simple Imaging in 3D. Stem Cells Int, 2019, 3106929.
  • Yin, Q., Xu, N., Xu, D., Dong, M., Shi, X., Wang, Y., Hao, Z., Zhu, S., Zhao, D., Jin, H., and Liu, W. (2020). Comparison of senescence-related changes between three- and two-dimensional cultured adipose-derived mesenchymal stem cells. Stem Cell Res Ther, 11, 226.
  • Yuan, L., Wu, Y., Fang, J., Wei, X., Gu, Q., El-Hamshary, H., Al-Deyab, S. S., Morsi, Y., and Mo, X. (2017). Modified alginate and gelatin cross-linked hydrogels for soft tissue adhesive. Artif Cells Nanomed Biotechnol, 45, 76-83.
  • Zhao, L., Hu, C., Zhang, P., Jiang, H., and Chen, J. (2019). Preconditioning strategies for improving the survival rate and paracrine ability of mesenchymal stem cells in acute kidney injury. J Cell Mol Med, 23, 720-730.

Aljinat-jelatin Kompozitlerin Mezenkimal Kök Hücreleri Üzerindeki Proliferatif Etkisinin Değerlendirilmesi

Yıl 2025, Cilt: 15 Sayı: 1, 119 - 132, 15.03.2025
https://doi.org/10.31466/kfbd.1496088

Öz

İki boyutlu (2D) kültür üzerinde yapılan geleneksel çalışmalar, hücre göçü, çözünür faktör gradyanı ve hücre-matris etkileşimleri dahil olmak üzere in vivo ortamın fizyolojik ve patofizyolojik özelliklerini yakından yansıttmaz. 3-boyutlu (3D) hücre kültürü, hücre göçünü teşvik etmek, biyomateryal sertligini degiştirmek veya hücre-matris etkileşimlerine izin vermek için aljinat hidrojelleri gibi 3D biyomateryalleri kullanarak bu dezavantajların üstesinden gelmektedir. Bu çalışmada, mezenkimal kok hücre canlılığını ve farklılaşma potansiyelini destekleyen doku mühendisliği tekniklerine olan ihtiyacı karşılamak için aljinat-jelatin kompozitleri içeren yeni bir 3-boyutlu platformun önerilmesi amaçlanmıştır. İlk bölümde farklı hidrojel bazlı biyomateryallerin absorbans spektrumları görünür ışık kullanılarak incelenmiştir. En iyi performansı gösteren hidrojeli bulduktan sonra çalışma, XTT canlılık testi ve canlı/ölü sitotoksisite testi kullanılarak hücre çoğalmasına odaklanılmıştır. Hücre canlılığı aljinat-jelatin, aljinat ve selüloz gibi iskelelerle karşılaştırıldığında, aljinat-jelatin hidrojelin mezenkimal kök hücrelerinin canlılığını arttırdığı tespit edildi. Bu artış, 2D kültürde büyütülen hücrelerle karşılaştırıldığında da aynı şekilde gözlendi. Bu çalışmadan elde edilen bulgular, literatürdeki diğer çalışmaların verileriyle tutarlıdır. Bu nedenle, aljinat-jelatin kompozitleri doku mühendisliğinde hücre proliferasyonunu iyileştirmek için umut verici bir aday olabilir.

Kaynakça

  • Aggarwal, S., and Pittenger, M. F. (2005). Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood, 105, 1815-1822.
  • Augst, A. D., Kong, H. J., and Mooney, D. J. (2006). Alginate hydrogels as biomaterials. Macromol Biosci, 6, 623-633.
  • Azoidis, I., Metcalfe, J., Reynolds, J., Keeton, S., Hakki, S. S., Sheard, J., and Widera, D. (2017). Three-dimensional cell culture of human mesenchymal stem cells in nanofibrillar cellulose hydrogels. MRS Communications, 7, 458-465.
  • Bhattacharya, M., Malinen, M. M., Lauren, P., Lou, Y-R., Kuisma, S. W., Kanninen, L., Lille, M., Corlu, A., GuGuen-Guillouzo, C., Ikkala, O., Laukkanen, A., Urtti, A., and Yliperttula, M. (2012). Nanofibrillar cellulose hydrogel promotes three-dimensional liver cell culture. Journal of Controlled Release, 164, 291-298.
  • Bowers, S. L., Banerjee, I., and Baudino, T. A. (2010). The extracellular matrix: at the center of it all. J Mol Cell Cardiol, 48, 474-482.
  • Brown, C., McKee, C., Bakshi, S., Walker, K., Hakman, E., Halassy, S., Svinarich, D., Dodds, R., Govind, C. K., and Chaudhry, G. R. (2019). Mesenchymal stem cells: Cell therapy and regeneration potential. J Tissue Eng Regen Med, 13, 1738-1755.
  • Chang, K. A., Lee, J. H., and Suh, Y. H. (2014). Therapeutic potential of human adipose-derived stem cells in neurological disorders. J Pharmacol Sci, 126, 293-301.
  • Chen, W., Pan, W., Wang, J., Cheng, L., Wang, J., Song, L., Hu, Y., and Ma, X. (2022). Emerging two-dimensional monoelemental materials (Xenes): Fabrication, modification, and applications thereof in the field of bioimaging as nanocarriers. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 14, e1750.
  • Daemi, H., and Barikani, M. (2012). Synthesis and characterization of calcium alginate nanoparticles, sodium homopolymannuronate salt and its calcium nanoparticles. Scientia Iranica, 19, 2023-2028.
  • Dimitriou, R., Jones, E., McGonagle, D., and Giannoudis, P. V. (2011). Bone regeneration: current concepts and future directions. BMC Med, 9, 66.
  • Dominici, M., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F. C., Krause, D. S., Deans, R. J., Keating, A., Prockop, D. J., and Horwitz, E. M. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 8, 315-317.
  • Draget, K. I., Skjåk-Bræk, G., and Stokke, B. T. (2006). Similarities and differences between alginic acid gels and ionically crosslinked alginate gels. Food Hydrocolloids, 20, 170-175.
  • Dranseikiene, D., Schrüfer, S., Schubert, D. W., Reakasame, S., and Boccaccini, A. R. (2020). Cell-laden alginate dialdehyde-gelatin hydrogels formed in 3D printed sacrificial gel. J Mater Sci Mater Med, 31, 31.
  • Dutta, R. C., and Dutta, A. K. (2009). Cell-interactive 3D-scaffold; advances and applications. Biotechnol Adv, 27, 334-339.
  • Finkemeier, C. G. (2002). Bone-grafting and bone-graft substitutes. The Journal of bone and joint surgery American volume, 84-a, 454-464.
  • Gugliandolo, A., Fonticoli, L., Trubiani, O., Rajan, T. S., Marconi G. D., Bramanti, P., Mazzon, E., Pizzicannella, J., and Diomede, F. (2021). Oral Bone Tissue Regeneration: Mesenchymal Stem Cells, Secretome, and Biomaterials. International journal of molecular sciences, 22, 5236.
  • Habibovic, P., and de Groot, K. (2007). Osteoinductive biomaterials--properties and relevance in bone repair. J Tissue Eng Regen Med, 1, 25-32.
  • Ho, T-C., Chang, C-C., Chan,, H-P., Chung, T-W., Shu, C-W., Chuang, K-P., Duh, T-H., Yang, M-H., and Tyan, Y-C. (2022). Hydrogels: Properties and Applications in Biomedicine. Molecules, 27, 2902.
  • Jose, G., Shalumon, K. T., and Chen, J-P. (2020). Natural Polymers Based Hydrogels for Cell Culture Applications. Current Medicinal Chemistry, 27, 2734-2776.
  • Kapałczyńska, M., Kolenda, T., Przybyła, W., Zajączkowska, M., Teresiak, A., Filas, V., Ibbs, M., Bliźniak, R., Łuczewski, Ł., and Lamperska, K. (2018). 2D and 3D cell cultures - a comparison of different types of cancer cell cultures. Arch Med Sci, 14, 910-919.
  • Kolk, A., Handschel, J., Drescher, W., Rothamel, D., Kloss, F., Blessmann, M., Heiland, M., Wolff, K-D., and Smeets, R. (2012). Current trends and future perspectives of bone substitute materials – From space holders to innovative biomaterials. Journal of Cranio-Maxillofacial Surgery, 40, 706-718.
  • Kuo, C. K., and Ma, P. X. (2001). Ionically crosslinked alginate hydrogels as scaffolds for tissue engineering: Part 1. Structure, gelation rate and mechanical properties. Biomaterials, 22, 511-521.
  • Liu, K., Wiendels, M., Yuan, H., Ruan, C., and Kouwer, P. H. J. (2022). Cell-matrix reciprocity in 3D culture models with nonlinear elasticity. Bioact Mater, 9, 316-331.
  • McKee, C., and Chaudhry, G. R. (2017). Advances and challenges in stem cell culture. Colloids Surf B Biointerfaces, 159, 62-77.
  • Neves, M. I., Moroni, L., and Barrias, C. C. (2020). Modulating Alginate Hydrogels for Improved Biological Performance as Cellular 3D Microenvironments. Front Bioeng Biotechnol, 8, 665.
  • Park, Y., Huh, K. M., and Kang, S. W. (2021). Applications of Biomaterials in 3D Cell Culture and Contributions of 3D Cell Culture to Drug Development and Basic Biomedical Research. International journal of molecular sciences, 22:
  • Sarker, B., Singh, R., Silva, R., Roether, J. A., Kaschta, J., Detsch, R., Schubert, D. W., Cicha, I., and Boccaccini, A. R. (2014). Evaluation of fibroblasts adhesion and proliferation on alginate-gelatin crosslinked hydrogel. PLoS One, 9, e107952.
  • Sarker, M., Izadifar, M., Schreyer, D., and Chen, X. (2018). Influence of ionic crosslinkers (Ca(2+)/Ba(2+)/Zn(2+)) on the mechanical and biological properties of 3D Bioplotted Hydrogel Scaffolds. J Biomater Sci Polym Ed, 29, 1126-1154.
  • Sheard, J. J., Bicer, M., Meng, Y., Frigo, A., Aguilar, R. M., Vallance, T. M., Iandolo, D., and Widera, D. (2019). Optically Transparent Anionic Nanofibrillar Cellulose Is Cytocompatible with Human Adipose Tissue-Derived Stem Cells and Allows Simple Imaging in 3D. Stem Cells Int, 2019, 3106929.
  • Yin, Q., Xu, N., Xu, D., Dong, M., Shi, X., Wang, Y., Hao, Z., Zhu, S., Zhao, D., Jin, H., and Liu, W. (2020). Comparison of senescence-related changes between three- and two-dimensional cultured adipose-derived mesenchymal stem cells. Stem Cell Res Ther, 11, 226.
  • Yuan, L., Wu, Y., Fang, J., Wei, X., Gu, Q., El-Hamshary, H., Al-Deyab, S. S., Morsi, Y., and Mo, X. (2017). Modified alginate and gelatin cross-linked hydrogels for soft tissue adhesive. Artif Cells Nanomed Biotechnol, 45, 76-83.
  • Zhao, L., Hu, C., Zhang, P., Jiang, H., and Chen, J. (2019). Preconditioning strategies for improving the survival rate and paracrine ability of mesenchymal stem cells in acute kidney injury. J Cell Mol Med, 23, 720-730.
Toplam 32 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Hayvan Hücre Kültürü ve Doku Mühendisliği
Bölüm Makaleler
Yazarlar

Mesude Biçer 0000-0001-7089-5661

Yayımlanma Tarihi 15 Mart 2025
Gönderilme Tarihi 5 Haziran 2024
Kabul Tarihi 24 Şubat 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 15 Sayı: 1

Kaynak Göster

APA Biçer, M. (2025). Assessing the Proliferative Impact of Alginate-Gelatin Composites on Mesenchymal Stromal Cells. Karadeniz Fen Bilimleri Dergisi, 15(1), 119-132. https://doi.org/10.31466/kfbd.1496088