Dynamic Nano–Bio Interfaces in Regenerative Medicine: From Molecular Interactions to Tissue-Specific Regeneration

Authors

https://doi.org/10.48313/bic.vi.75

Abstract

Nanomaterials have emerged as versatile platforms for modulating biological processes and creating advanced interfaces for tissue regeneration. However, their biological behavior is not determined solely by their intrinsic physicochemical properties but evolves dynamically following interaction with the biological environment. This review provides a comprehensive perspective on nano–bio interfaces, emphasizing the mechanisms through which nanomaterials interact with proteins, cellular membranes, intracellular compartments, immune cells, stem cells, and tissue microenvironments. Particular attention is given to the formation and evolution of the protein corona, cellular recognition and uptake, intracellular trafficking, oxidative and inflammatory responses, and interactions with the immune system. The influence of nanomaterial-mediated signals on stem-cell adhesion, proliferation, migration, mechanotransduction, metabolism, and lineage-specific differentiation is further discussed. Tissue-specific applications in bone, cartilage, neural, cardiac, vascular, and skin regeneration are examined to highlight how nanomaterial properties can be adapted to distinct biological and mechanical environments. In addition, the review addresses nanomaterial degradation, persistence, long-term biocompatibility, nanotoxicity, reproducibility, and challenges associated with clinical translation. Emerging strategies involving three-dimensional models, organ-on-chip platforms, single-cell and spatial omics, artificial intelligence, and adaptive nanomaterials are also considered. Overall, this review emphasizes a shift from designing nanomaterials solely for structural support or passive biocompatibility toward the development of dynamic, biologically instructive, and tissue-specific nano–bio interfaces capable of actively regulating cellular and immune responses. Such a mechanistic and predictive approach may facilitate the development of safer and more effective nanomaterials for next-generation regenerative medicine. 

Keywords:

Nano–bio interface, Nanomaterials, Tissue regeneration, Stem cells, Immune response, Protein corona, Nanotoxicity

References

  1. [1] Begum, A., Islam, Z., & Ahmed, S. (2026). Cell material interactions at the nano-bio interface: Implications for regenerative medicine. Journal of biomedical and techno nanomaterials, 3(2), 124–135. https://doi.org/10.70177/jbtn.v3i2.3958
  2. [2] Singh, D. (2025). Nano-bio interfaces: Pioneering targeted approaches for disease treatment and prevention. Journal of macromolecular science, part b, 64(12), 1459–1476. https://doi.org/10.1080/00222348.2024.2395693
  3. [3] Kumar, R., Igwegbe, C. A., & Khandel, S. K. (2024). Nanotherapeutic and nano-bio interface for regeneration and healing. Biomedicines, 12(12), 2927. https://doi.org/10.3390/biomedicines12122927
  4. [4] Makki, H. H. (2026). Smart nanobiocatalysts for waste-to-biofuel conversion: Integrating nano-bio interfaces and AI-driven design. Frontiers in bioengineering and biotechnology, 14, 1847169. https://doi.org/10.3389/fbioe.2026.1847169
  5. [5] Kwara, P. A. (2024). Exploring nano bio interfaces in sustainable food systems: Enhancing food security, reducing waste, and minimizing environmental impact. International journal of science, architecture, technology and environment, 2(11), 129-141. https://doi.org/10.63680/ijsate0124008.10
  6. [6] Habeeb, M., Vengateswaran, H. T., Kumbhar, S. T., You, H. W., Asane, G. S., & Aher, K. B. (2025). Nano-bio interactions: Understanding their dynamic connections. In Theranostics nanomaterials in drug delivery (pp. 11–25). Elsevier. https://doi.org/10.1016/B978-0-443-22044-9.00025-5
  7. [7] Yang, X., Tsai, C. T., Yang, Y., Zhang, W., You, H., Forró, C., ... & Cui, B. (2026). Nano-bio interfaces for electrical and biochemical signal transduction. Nature reviews bioengineering, 4(3), 250-268. https://doi.org/10.1038/s44222-025-00374-7
  8. [8] Chen, C. (2025). From mapping nano-bio journeys to directing their destiny. Nano letters, 25(51), 17537–17539. https://doi.org/10.1021/acs.nanolett.5c05474
  9. [9] Wu, R., Dong, M., & Liu, L. (2023). Nano-bio interface of molybdenum disulfide for biological applications. Coatings, 13(6), 1122. https://doi.org/10.3390/coatings13061122
  10. [10] Chen, X., Xu, L., & Shi, H. (2025). Emerging biomaterials and bio-nano interfaces in pulmonary hypertension therapy: Transformative strategies for personalized treatment. Frontiers in bioengineering and biotechnology, 13, 1567783. https://doi.org/10.3389/fbioe.2025.1567783
  11. [11] Savolainen, K., Backman, U., Brouwer, D., Fadeel, B., Fernandes, T., Kuhlbusch, T., ... & Pylkkänen, L. (2013). Nanosafety in Europe 2015–2025: Towards safe and sustainable nanomaterials and nanotechnology innovations. Finnish institute of occupational health, 218, 1-215. https://d1wqtxts1xzle7.cloudfront.net/39590196/EU_nanosafety_2015-2025-libre.pdf
  12. [12] Goyal, A., Meena, P. K., & Shelare, S. (2025). Nanotechnology in biofuel production: Enhancing efficiency and sustainability through nanomaterials. Journal of cluster science, 36(3), 87. https://doi.org/10.1007/s10876-025-02797-z
  13. [13] Boretti, A. (2025). A narrative review of breakthroughs and future horizons in zero-dimensional nanomaterials. Optical and quantum electronics, 57(6), 370. https://doi.org/10.1007/s11082-025-08288-9
  14. [14] Khan, A., Ashiq, B., Qadri, T. A., Khattak, W. A., Anas, M., Khan, R. A., ... & Maaza, M. (2025). Nanotechnology solutions for advancing sustainable development goals (SDGs): Integrating nanomaterials for global sustainability. BioNanoScience, 15(4), 590. https://doi.org/10.1007/s12668-025-02214-9
  15. [15] Goyal, A., Meena, P. K., Shelare, S., & Kumar, S. (2025). Advancing biofuel production through nanomaterials: A review of efficiency improvements, challenges, and future directions. Nanocomposites, 11(1), 151–172. https://doi.org/10.1080/20550324.2025.2518755
  16. [16] Aggarwal, K., Brahma, A., Nisha, Sharma, Y., Rajput, P., Sachdeva, B., ... & Singh, S. (2025). Recent progress in copper nanomaterials: Catalysis, energy, biomedicine, and environmental applications. Materials advances, 6(24), 9296-9339.https://doi.org/10.1039/d5ma00484e
  17. [17] Antony Jose, S., Cowan, N., Davidson, M., Godina, G., Smith, I., Xin, J., & Menezes, P. L. (2025). A comprehensive review on cellulose nanofibers, nanomaterials, and composites: Manufacturing, properties, and applications. Nanomaterials, 15(5), 356. https://doi.org/10.3390/nano15050356
  18. [18] Ashour, A. A., Tayeb, F. J., Felemban, M. F., & Shafie, A. (2025). Nanomaterial-based biosensors for cancer diagnosis: Trends and innovations (2022-2025). Microchimica acta, 192(7), 404. https://doi.org/10.1007/s00604-025-07276-w
  19. [19] Akhter, P., Arshad, A., & Tahir, M. (2025). Innovative nanomaterials for sustainable environment for reducing the smog effects: A technical review. Environmental science and pollution research, 32(31), 18582–18603. https://doi.org/10.1007/s11356-025-36780-y
  20. [20] Zhu, C., & Wang, X. (2025). Nanomaterial ZnO synthesis and its photocatalytic applications: A review. Nanomaterials, 15(9), 682. https://doi.org/10.3390/nano15090682
  21. [21] Parvin, N., Joo, S. W., & Mandal, T. K. (2025). Nanomaterial-based strategies to combat antibiotic resistance: Mechanisms and applications. Antibiotics, 14(2), 207. https://doi.org/10.3390/antibiotics14020207
  22. [22] Al-Harbi, N., & Abd-Elrahman, N. K. (2025). Physical methods for preparation of nanomaterials, their characterization and applications: A review. Journal of umm al-qura university for applied sciences, 11(2), 356–377. https://doi.org/10.1007/s43994-024-00165-7
  23. [23] Tapeh, S. M. T., Baei, M. S., & Keshel, S. H. (2021). Synthesis of thermogel modified with biomaterials as carrier for hUSSCs differentiation into cardiac cells: Physicomechanical and biological assessment. Materials science and engineering: C, 119, 111517. https://doi.org/10.1016/j.msec.2020.111517
  24. [24] Kar, N., & Skrabalak, S. E. (2025). Synthetic methods for high-entropy nanomaterials. Nature reviews materials, 10(9), 638–653. https://doi.org/10.1038/s41578-025-00829-8
  25. [25] Takhar, V., & Singh, S. (2025). Nanomaterials ROS: A comprehensive review for environmental applications. Environmental science: Nano, 12(5), 2516–2550. https://doi.org/10.1039/d5en00049a
  26. [26] De Silva, M., Cao, G., & Tam, K. C. (2025). Nanomaterials for the removal and detection of heavy metals: A review. Environmental science: Nano, 12(4), 2154–2176. https://doi.org/10.1039/d4en01041h
  27. [27] Jiang, Z., Xiang, H., & Tang, X. (2025). Smart inorganic nanomaterials for tumor microenvironment modulation. Inorganics, 13(10), 337. https://doi.org/10.3390/inorganics13100337
  28. [28] Cui, L., Lyu, T. J., Fu, B., Wang, Y., Qu, Q., Wang, F., ... & Fan, J. (2025). Advances and challenges in decellularized adipose tissue based composite hydrogels for adipose tissue regeneration: A review over the last fifteen years. Theranostics, 15(18), 9508. https://doi.org/10.7150/thno.120300
  29. [29] Zaman, W., Ayaz, A., & Park, S. (2025). Nanomaterials in agriculture: A pathway to enhanced plant growth and abiotic stress resistance. Plants, 14(5), 716. https://doi.org/10.3390/plants14050716
  30. [30] Niknejad, K., Sharifzadeh, B. M., & Motallebi, T. T. S. (2018). Synthesis of Metformin Hydrochloride nanoliposomes: Evaluation of physicochemical characteristics and release kinetics. International journal of nano dimension, 9(3), 298-313. (In Persian). https://www.sid.ir/paper/322408/en
  31. [31] Tian, G., Yang, Z., Deng, H., Sui, X., Liu, S., & Guo, Q. (2025). Bibliometric analysis of apoptotic vesicles for tissue regeneration research: Trends and insights from 1991 to 2023. Stem cells international, 2025(1), 3190427. https://doi.org/10.1155/sci/3190427
  32. [32] Barik, D., & Konkimalla, V. B. (2025). Next-generation nanomaterials in biology: From tissue regeneration to targeted cancer therapy. IUBMB life, 77(11), e70071. https://doi.org/10.1002/iub.70071
  33. [33] Jiang, Y., & Ke, D. (2025). Comprehensive exploration of biomaterials and nanobiotechnology for tissue regeneration and organ reconstruction. Frontiers in bioengineering and biotechnology, 13, 1710115. https://doi.org/10.3389/fbioe.2025.1710115
  34. [34] Alhumaidan, A. A., Alam, B. F., Alsuwaiyan, A., Aljoghaiman, E. A., Helmi, M., & Ali, S. (2025). Scientific research trend on guided tissue regeneration: A bibliometric analysis. European journal of dentistry, 19(02), 409–419. https://doi.org/10.1055/s-0044-1791529
  35. [35] Laurencin, C. T., Whitfield, T., Argyrou, C., & Hosseini, F. S. (2025). Regenerative engineering AI: A new paradigm for the future of tissue regeneration. Frontiers of chemical science and engineering, 19(10), 95. https://doi.org/10.1007/s11705-025-2566-x
  36. [36] Kopeina, G. S., Efimenko, A. Y., Tkachuk, V. A., & Zhivotovsky, B. (2025). Programmed cell death and tissue regeneration: A link that should be resolved. Physiological reviews, 105(4), 2377–2412. https://doi.org/10.1152/physrev.00036.2024
  37. [37] Alsuraifi, A., Mouzan, M. M., Ali, A. A. A., Algzaare, A., Aqeel, Z., Ezzat, D., & Ayad, A. (2025). Revolutionizing tooth regeneration: Innovations from stem cells to tissue engineering. Regenerative engineering and translational medicine, 11(3), 625–650. https://doi.org/10.1007/s40883-024-00382-w
  38. [38] Li, S., Lu, L., Xiong, Y., & Xiao, J. (2025). Nanomedicine-based immunotherapy for tissue regeneration. Burns & trauma, 13, tkaf015. https://doi.org/10.1093/burnst/tkaf015
  39. [39] Kirkeby, A., Main, H., & Carpenter, M. (2025). Pluripotent stem-cell-derived therapies in clinical trial: A 2025 update. Cell stem cell, 32(1), 10–37. https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(24)00445-4
  40. [40] Wang, Y., Zhu, J., Ma, Q., Zhou, W., Yang, L., Sheng, S., ... & Xia, Z. (2025). Trends in mesenchymal stem cell-derived extracellular vesicles clinical trials 2014–2024: Is efficacy optimal in a narrow dose range? Frontiers in medicine, 12, 1625787. https://doi.org/10.3389/fmed.2025.1625787
  41. [41] Lee, H., Kim, B., Park, J., Park, S., Yoo, G., Yum, S., ... & Youn, B. (2025). Cancer stem cells: Landscape, challenges and emerging therapeutic innovations. Signal transduction and targeted therapy, 10(1), 248. https://doi.org/10.1038/s41392-025-02360-2
  42. [42] Trigo, C. M., Rodrigues, J. S., Camões, S. P., Solá, S., & Miranda, J. P. (2025). Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? Journal of advanced research, 70, 103–124. https://doi.org/10.1016/j.jare.2024.05.004

Published

2024-03-08

Issue

Vol. 1 No. 1 (2024): Biocompounds

Section

Articles

How to Cite

Pourqasem, M. . (2024). Dynamic Nano–Bio Interfaces in Regenerative Medicine: From Molecular Interactions to Tissue-Specific Regeneration. Biocompounds, 1(1), 74-103. https://doi.org/10.48313/bic.vi.75