A Review of Innovations In Tissue Engineering And Regenerative Medicine Include The Use Of Biomaterials, The Creation Of Scaffolds And Artificial Intelligence In Stem Cells
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Abstract
Over the past two decades, tissue engineering and regenerative medicine have been among the fastest growing scientific disciplines, driven by the integration of biomaterials, stem cells, scaffolding technologies and artificial intelligence (AI) to reconstruct tissues and restore their function. Natural biomaterials offer a rich environment for biosignatures but are limited in structural applications due to poor mechanical stability. Synthetic material, on the other hand, offer flexible control over mechanical properties and degradation rates, but with limited inherent biocompatibility, making hybrid biomaterials a promising option. Electrospinning and 3D and 4D bioprinting technologies have contributed to the development of scaffolds that mimic the extracellular matrix, although challenges related to deep porosity, mechanical stability, and uniform printing persist. Mesenchymal Stem Cells (MSCs) are the most common clinical choice, while induced pluripotent stem cell (iPSCs) hold potential in personalized medicine, despite concerns about genomic integrity. Exosome based therapy represent a safe and effective alternative to whole cell therapy. AI enables the prediction of biomaterial and cell behavior, enhances bioprinting, and allows for virtual model testing via digital twins. However, widespread clinical use is hamepered by a lack of regulatory standards and data, as well as the difficulty in understanding the models. Challenges in tissue engineering include blood supply, immune response and ethical and legal issues. Research underscores the need for coordinated, multidisciplinary research efforts. This integration represents the foundation for a new generation of regenerative medicine capable of overcoming current obstacles and restoring vital functions with precision and sustainability.
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References
Murphy, S. V., & Atala, A. (2014). 3D bioprinting of tissues and organs. Nature Biotechnology,
(8), 773–785. https://doi.org/10.1038/nbt.2958
Zhang, Y. S., Yue, K., Aleman, J., et al. (2017). 3D bioprinting for tissue and organ fabrication.
Annals of Biomedical Engineering, 45(1), 148–163. https://doi.org/10.1007/s10439-016-1612-8
Groll, J., Boland, T., Blunk, T., et al. (2016). Biofabrication: reappraising the definition of an
evolving field. Biofabrication, 8(1), 013001. https://doi:10.1088/1758-5090/8/1/013001
Mandrycky, C., Wang, Z., Kim, K., & Kim, D. H. (2016). 3D bioprinting for engineering complex
issues. Biotechnology advances, 34(4), 422-434. https://doi.org/10.1016/j.biotechadv.2015.12.011
Daly, A. C., Prendergast, M. E., Hughes, A. J., & Burdick, J. A. (2021). Bioprinting for the
biologist. Cell, 184(1), 18–32. https://doi.org/10.1016/j.cell.2020.12.002
Xue, J., Wu, T., Dai, Y., & Xia, Y. (2019). Electrospinning and electrospun nanofibers: methods,
materials, and applications. Chemical reviews, 119(8), 5298-5415.
https://doi.org/10.1021/acs.chemrev.8b00593
Li, D., & Xia, Y. (2004). Electrospinning of nanofibers: reinventing the wheel? Advanced Materials,
(14), 1151–1170. https://doi.org/10.1002/adma.200400719
Huang, Z. M., Zhang, Y. Z., Kotaki, M., & Ramakrishna, S. (2003). A review on polymer
nanofibers by electrospinning. Composites Science and Technology, 63(15), 2223–2253.
https://doi.org/10.1016/S0266-3538(03)00178-7
Bhardwaj, N., & Kundu, S. C. (2010). Electrospinning: A fascinating fiber fabrication technique.
Biotechnology Advances, 28(3), 325–347. https://doi.org/10.1016/j.biotechadv.2010.01.004
Pant, H. R., Neupane, M. P., Pant, B., et al. (2011). Electrospun nanofibers for biomedical
applications. Polymer Reviews, 51(3), 135–176.
Bianco, P., Robey, P. G., & Simmons, P. J. (2008). Mesenchymal stem cells: Revisiting history,
concepts, and assays. Cell Stem Cell, 2(4), 313–319. https://doi.org/10.1016/j.stem.2008.03.002
Caplan, A. I. (1991). Mesenchymal stem cells. Journal of Orthopaedic Research, 9(5), 641–650.
https://doi.org/10.1002/jor.1100090504
Caplan, A. I., & Correa, D. (2011). The MSC: An injury drugstore. Cell Stem Cell, 9(1), 11–15.
https://doi.org/10.1016/j.stem.2011.06.008
Dominici, M., Le Blanc, K., Mueller, I., et al. (2006). Minimal criteria for defining multipotent
mesenchymal stromal cells. Cytotherapy, 8(4), 315–317.
https://doi.org/10.1080/14653240600855905
Pittenger, M. F., Mackay, A. M., Beck, S. C., et al. (1999). Multilineage potential of adult human
mesenchymal stem cells. Science, 284(5411), 143–147.
https://doi.org/10.1126/science.284.5411.143
Engler, A. J., Sen, S., Sweeney, H. L., & Discher, D. E. (2006). Matrix elasticity directs stem cell
lineage specification. Cell, 126(4), 677–689. https://doi.org/10.1016/j.cell.2006.06.044
Discher, D. E., Janmey, P., & Wang, Y.-L. (2005). Tissue cells feel and respond to the stiffness of
their substrate. Science, 310(5751), 1139–1143. https://doi.org/10.1126/science.1116995
Trappmann, B., & Chen, C. S. (2013). How cells sense extracellular matrix stiffness. Current
Opinion in Cell Biology, 25(5), 582–588. https://doi.org/10.1016/j.ceb.2013.06.002
Yue, K., Trujillo-de Santiago, G., Alvarez, M. M., et al. (2015). Synthesis, properties, and
biomedical applications of gelatin methacryloyl (GelMA) hydrogels. Biomaterials, 73, 254–271.
https://doi.org/10.1016/j.biomaterials.2015.08.045
O’Brien, F. J. (2011). Biomaterials & scaffolds for tissue engineering. Materials Today, 14(3), 88–
https://doi.org/10.1016/S1369-7021(11)70058-X
Hutmacher, D. W. (2000). Scaffolds in tissue engineering bone and cartilage. Biomaterials,
(24), 2529–2543. https://doi.org/10.1016/S0142-9612(00)00121-6
Woodruff, M. A., & Hutmacher, D. W. (2010). The return of a forgotten polymer—polycaprolactone
in the 21st century. Progress in Polymer Science, 35(10), 1217–1256.
https://doi.org/10.1016/j.progpolymsci.2010.04.002
Kazem Mehdi Kazem & et al. Libyan Journal of Medical and Applied Sciences 4(1) (2026), 1-15
Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse fibroblasts
by defined factors. Cell, 126(4), 663–676. https://doi.org/10.1016/j.cell.2006.07.024
Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., et al. (1998). Embryonic stem cell lines derived
from human blastocysts. Science, 282(5391), 1145–1147.
https://doi.org/10.1126/science.282.5391.1145
Nosrati, H., Sefidi, N., Sharafi, S., et al. (2021). Artificial intelligence in regenerative medicine:
Applications and perspectives. Stem Cell Research & Therapy, 12, 427.
https://doi.org/10.1186/s13287-021-02543-9
Wu, Y., Ding, X., Wang, Y., & Ouyang, D. (2023). Harnessing machine learning in tissue
engineering. Burns & Trauma, 11, tkad040. https://doi.org/10.1093/burnst/tkad040
Yang, Y., Wu, S., Yu, L., et al. (2022). Machine learning for materials science. Nature Reviews
Materials, 7, 449–469. https://doi.org/10.1007/s42243-024-01179-5
Gelmi, A., & Schutt, C. E. (2021). Stimuli-responsive biomaterials: Scaffolds for stem cell control.
Advanced Healthcare Materials, 10(1), e2001125. https://doi.org/10.1002/adhm.202001125
Ramesh, S., Mehendale, N., McGowan, S., et al. (2021). Artificial intelligence in 3D bioprinting.
Biofabrication, 13(4), 042002. https://doi.org/10.1088/1758-5090/ac1fcb
Thiele, J., Ma, Y., Bruekers, S. M. C., et al. (2014). Designer hydrogels for cell cultures. Advanced
Materials, 26(1), 125–148. https://doi.org/10.1002/adma.201302958
Crapo, P. M., Gilbert, T. W., & Badylak, S. F. (2011). An overview of tissue and whole organ
decellularization processes. Biomaterials, 32(12), 3233–3243.
https://doi.org/10.1016/j.biomaterials.2011.01.057
Badylak, S. F., Taylor, D., & Uygun, K. (2011). Whole-organ tissue engineering: Decellularization
and recellularization. Annual Review of Biomedical Engineering, 13, 27–53.
https://doi.org/10.1146/annurev-bioeng-071910-124743
Daly, A. C., Davidson, M. D., & Burdick, J. A. (2021). 3D bioprinting of high cell-density
heterogeneous tissue models. Nature Communications, 12, 753. https://doi.org/10.1038/s41467-
-21029-2
Kang, H. W., Lee, S. J., Ko, I. K., et al. (2016). A 3D bioprinting system to produce human-scale
tissue constructs. Nature Biotechnology, 34(3), 312–319. https://doi.org/10.1038/nbt.3413
Langer, R., & Vacanti, J. P. (1993). Tissue engineering. Science, 260(5110), 920–926.
Mason, C., & Dunnill, P. (2008). A brief definition of regenerative medicine. Regenerative
Medicine, 3(1), 1–5. https://doi.org/10.2217/17460751.3.1.1
Williams, D. F. (2019). Challenges with the development of biomaterials for sustainable tissue
engineering. Frontiers in Bioengineering and Biotechnology, 7, 127.
https://doi.org/10.3389/fbioe.2019.00127
Martelli, A., Bellucci, D., & Cannillo, V. (2025). The role of artificial intelligence in biomaterials
science: A review. Polymers (Basel), 17(19), 2668. https://doi.org/10.3390/polym17192668
Zhou, B., Li, X., Pan, Y., He, B., & Gao, B. (2025). Artificial intelligence-assisted next-generation
biomaterials: From design and preparation to medical applications. Colloids and Surfaces B:
Biointerfaces, 114970. https://doi.org/10.1016/j.colsurfb.2025.114970