The Novel Membrane-Type Micro-system to Assess the Bonus Effect of Physiological and Physical Stimuli on Bone Regeneration

Abstract

The periosteal progenitor cell is suitable for bone tissue regeneration duo to its multipotent differentiation in osteogenesis and chondrogenesis. It was found that both physical and physiological stimuli can induce the differentiation of periosteal progenitor cells. However, the combined-effect of these two stimuli is not clear. The imitation of the nature movement—the cyclic tensile strain stimulation and the multiple growth factors producing cells—adipose-derived stem cells (ADSCs) were used as physical and physiological stimuli to investigate the differentiation of rabbit periosteal cells in this study. For this, a new membrane-type micro-system was invented to provide a simple examination platform for both factors in one single system. The specific rectangular culture chamber not only provided two different types of cells to grow separately but also delivered the single axial tensile strain generated in the micro-system to the cells. It was found that application of either physical or physiological stimuli alone was sufficient to induce the differentiation of periosteal cells. The low tensile strain (4, 5, 6 kPa) led to osteogenesis whereas high tensile strain (7 kPa) induced chondrogenesis. Even though the co-culture of ADSCs only induced osteogenic differentiation of periosteal cells, the co-culture of ADSCs to tensile strain treated periosteal cells further strengthened the osteogenic and chondrogenic differentiation potent in low and high tensile strain, respectively. This study provided the pre-clinical evidence of the stem cell therapy and continuous exercise in cell level bone tissue regeneration.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

References

  1. 1.

    Simon, T.M., Van Sickle, D.C., Kunishima, D.H., Jackson, D.W.: Cambium cell stimulation from surgical release of the periosteum. J. Orthop. Res. 21, 470–480 (2003)

    PubMed  Article  PubMed Central  Google Scholar 

  2. 2.

    Arnsdorf, E.J., Jones, L.M., Carter, D.R., Jacobs, C.R.: The periosteum as a cellular source for functional tissue engineering. Tissue Eng. Part A 15, 2637–2642 (2009)

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  3. 3.

    Castro-Silva, I.I., Zambuzzi, W.F., de Oliveira Castro, L., Granjeiro, J.M.: Periosteal-derived cells for bone bioengineering: a promising candidate. Clin. Oral Implants Res. 23, 1238–1242 (2012)

    PubMed  Article  PubMed Central  Google Scholar 

  4. 4.

    Ferretti, C., Mattioli-Belmonte, M.: Periosteum derived stem cells for regenerative medicine proposals: boosting current knowledge. World J. Stem Cells 6, 266 (2014)

    PubMed  PubMed Central  Article  Google Scholar 

  5. 5.

    Ueno, T., Kagawa, T., Fukunaga, J., Mizukawa, N., Sugahara, T., Yamamoto, T.: Evaluation of osteogenic/chondrogenic cellular proliferation and differentiation in the xenogeneic periosteal graft. Ann. Plast. Surg. 48, 539–545 (2002)

    PubMed  Article  PubMed Central  Google Scholar 

  6. 6.

    Ueno, T., Kagawa, T., Fukunaga, J., Mizukawa, N., Kanou, M., Fujii, T., Sugahara, T., Yamamoto, T.: Regeneration of the mandibular head from grafted periosteum. Ann. Plast. Surg. 51, 77–83 (2003)

    PubMed  Article  PubMed Central  Google Scholar 

  7. 7.

    Ngdag, A.M.H., Saim, A.B., Tan, K.-K., Tan, G., Mokhtar, S.A., Rose, I.M., Othman, F., Idrus, R.B.H.: Comparison of bioengineered human bone construct from four sources of osteogenic cells. J. Orthop. Sci. 10, 192–199 (2005)

    Article  Google Scholar 

  8. 8.

    Shen, T., Qiu, L., Chang, H., Yang, Y., Jian, C., Xiong, J., Zhou, J., Dong, S.: Cyclic tension promotes osteogenic differentiation in human periodontal ligament stem cells. Int. J. Clin. Exp. Pathol. 7, 7872–7880 (2014)

    PubMed  PubMed Central  Google Scholar 

  9. 9.

    Liu, X., Chen, W., Zhou, Y., Tang, K., Zhang, J.: Mechanical tension promotes the osteogenic differentiation of rat tendon-derived stem cells through the Wnt5a/Wnt5b/JNK signaling pathway. Cell. Physiol. Biochem. 36, 517–530 (2015)

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  10. 10.

    Haasper, C., Jagodzinski, M., Drescher, M., Meller, R., Wehmeier, M., Krettek, C., Hesse, E.: Cyclic strain induces FosB and initiates osteogenic differentiation of mesenchymal cells. Exp. Toxicol. Pathol. 59, 355–363 (2008)

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  11. 11.

    Arnsdorf, E.J., Tummala, P., Kwon, R.Y., Jacobs, C.R.: Mechanically induced osteogenic differentiation–the role of RhoA, ROCKII and cytoskeletal dynamics. J. Cell Sci. 122, 546–553 (2009)

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  12. 12.

    Hoey, D.A., Tormey, S., Ramcharan, S., O’Brien, F.J., Jacobs, C.R.: Primary cilia-mediated mechanotransduction in human mesenchymal stem cells. Stem Cells 30, 2561–2570 (2012)

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  13. 13.

    Lee, J.-M., Kim, M.-G., Byun, J.-H., Kim, G.-C., Ro, J.-H., Hwang, D.-S., Choi, B.-B., Park, G.-C., Kim, U.-K.: The effect of biomechanical stimulation on osteoblast differentiation of human jaw periosteum-derived stem cells. Maxillofac. Plast. Reconstr. Surg. 39, 1–9 (2017)

    PubMed  PubMed Central  Article  Google Scholar 

  14. 14.

    Matthews, B., Wee, N.K.Y., Widjaja, V., Price, J., Kalajzic, I., Windahl, S.: αSMA osteoprogenitor cells contribute to the increase in osteoblast numbers in response to mechanical loading. Calcif. Tissue Int. 106, 208–217 (2020)

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  15. 15.

    Kanno, T., Takahashi, T., Ariyoshi, W., Tsujisawa, T., Haga, M., Nishihara, T.: Tensile mechanical strain up-regulates Runx2 and osteogenic factor expression in human periosteal cells: implications for distraction osteogenesis. J. Oral Maxillofac. Surg. 63, 499–504 (2005)

    PubMed  Article  PubMed Central  Google Scholar 

  16. 16.

    Quarto, N., Wan, D.C., Kwan, M.D., Panetta, N.J., Li, S., Longaker, M.T.: Origin matters: differences in embryonic tissue origin and Wnt signaling determine the osteogenic potential and healing capacity of frontal and parietal calvarial bones. J. Bone Miner. Res. 25, 1680–1694 (2010)

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Maeda, K., Takahashi, N., Kobayashi, Y.: Roles of Wnt signals in bone resorption during physiological and pathological states. J. Mol. Med. 91, 15–23 (2013)

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  18. 18.

    Hu, K., Olsen, B.R.: The roles of vascular endothelial growth factor in bone repair and regeneration. Bone 91, 30–38 (2016)

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  19. 19.

    Mussano, F., Genova, T., Corsalini, M., Schierano, G., Pettini, F., Di, V., D., Carossa, S. : Cytokine, chemokine, and growth factor profile characterization of undifferentiated and osteoinduced human adipose-derived stem cells. Stem Cells Int. (2017). https://doi.org/10.1155/2017/6202783

    Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Wu, A.C., Raggatt, L.J., Alexander, K.A., Pettit, A.R.: Unraveling macrophage contributions to bone repair. BoneKEy Rep. (2013). https://doi.org/10.1038/bonekey.2013.107

    Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Kon, T., Cho, T.J., Aizawa, T., Yamazaki, M., Nooh, N., Graves, D., Gerstenfeld, L.C., Einhorn, T.A.: Expression of osteoprotegerin, receptor activator of NF-κB ligand (osteoprotegerin ligand) and related proinflammatory cytokines during fracture healing. J. Bone Miner. Res. 16, 1004–1014 (2001)

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  22. 22.

    Cho, T.J., Gerstenfeld, L.C., Einhorn, T.A.: Differential temporal expression of members of the transforming growth factor β superfamily during murine fracture healing. J. Bone Miner. Res. 17, 513–520 (2002)

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  23. 23.

    Kolar, P., Gaber, T., Perka, C., Duda, G.N., Buttgereit, F.: Human early fracture hematoma is characterized by inflammation and hypoxia. Clin. Orthop. Relat. Res. 469, 3118–3126 (2011)

    PubMed  PubMed Central  Article  Google Scholar 

  24. 24.

    Zhang, H., Kot, A., Lay, Y.A.E., Fierro, F.A., Chen, H., Lane, N.E., Yao, W.: Acceleration of fracture healing by overexpression of basic fibroblast growth factor in the mesenchymal stromal cells. Stem Cells Transl. Med. 6, 1880–1893 (2017)

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  25. 25.

    Cui, F., Wang, X., Liu, X., Dighe, A.S., Balian, G., Cui, Q.: VEGF and BMP-6 enhance bone formation mediated by cloned mouse osteoprogenitor cells. Growth Factors 28, 306–317 (2010)

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  26. 26.

    Li, F., Zhou, C., Xu, L., Tao, S., Zhao, J., Gu, Q.: Effect of stem cell therapy on bone mineral density: a meta-analysis of preclinical studies in animal models of osteoporosis. PLoS ONE 11, e0149400 (2016)

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  27. 27.

    Ye, X., Zhang, P., Xue, S., Xu, Y., Tan, J., Liu, G.: Adipose-derived stem cells alleviate osteoporosis by enchancing osteogenesis and inhibiting adipogenesis in a rabbit model. Cytotherapy 16, 1643–1655 (2014)

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  28. 28.

    Liu, H.-Y., Chiou, J.-F., Wu, A.T., Tsai, C.-Y., Leu, J.-D., Ting, L.-L., Wang, M.-F., Chen, H.-Y., Lin, C.-T., Williams, D.F.: The effect of diminished osteogenic signals on reduced osteoporosis recovery in aged mice and the potential therapeutic use of adipose-derived stem cells. Biomaterials 33, 6105–6112 (2012)

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  29. 29.

    Chen, D., Zhang, X., He, Y., Lu, J., Shen, H., Jiang, Y., Zhang, C., Zeng, B.: Co-culturing mesenchymal stem cells from bone marrow and periosteum enhances osteogenesis and neovascularization of tissue-engineered bone. J. Tissue Eng. Regen. Med. 6, 822–832 (2012)

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  30. 30.

    Li, N., Song, J., Zhu, G., Li, X., Liu, L., Shi, X., Wang, Y.: Periosteum tissue engineering—a review. Biomater. Sci. 4, 1554–1561 (2016)

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  31. 31.

    Orciani, M., Fini, M., Di Primio, R., Mattioli-Belmonte, M.: Biofabrication and bone tissue regeneration: cell source, approaches, and challenges. Front. Bioeng. Biotechnol. 5, 17 (2017)

    PubMed  PubMed Central  Article  Google Scholar 

  32. 32.

    Torino, S., Corrado, B., Iodice, M., Coppola, G.: Pdms-based microfluidic devices for cell culture. Inventions 3, 65 (2018)

    Article  Google Scholar 

  33. 33.

    Kim, Y.C., Kang, J.H., Park, S.-J., Yoon, E.-S., Park, J.-K.: Microfluidic biomechanical device for compressive cell stimulation and lysis. Sens. Actuators B Chem. 128, 108–116 (2007)

    CAS  Article  Google Scholar 

  34. 34.

    Kim, Y.C., Park, S.-J., Park, J.-K.: Biomechanical analysis of cancerous and normal cells based on bulge generation in a microfluidic device. Analyst 133, 1432–1439 (2008)

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  35. 35.

    Gao, X., Zhang, X., Tong, H., Lin, B., Qin, J.: A simple elastic membrane-based microfluidic chip for the proliferation and differentiation of mesenchymal stem cells under tensile stress. Electrophoresis 32, 3431–3436 (2011)

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  36. 36.

    Chiu, C.-H., Liu, J.-L., Chang, C.-H., Lei, K.F., Chen, A.C.-Y.: Investigation of osteogenic activity of primary rabbit periosteal cells stimulated by multi-axial tensile strain. Biomed. Microdevices 19, 13 (2017)

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  37. 37.

    Chiu, C.-H., Tong, Y.-W., Yeh, W.-L., Lei, K.F., Chen, A.C.-Y.: Self-renewal and differentiation of adipose-derived stem cells (ADSCs) stimulated by multi-axial tensile strain in a pneumatic microdevice. Micromachines 9, 607 (2018)

    PubMed Central  Article  Google Scholar 

  38. 38.

    Chiu, C.-H., Tong, Y.-W., Yu, J.-F., Lei, K.F., Chen, A.C.-Y.: Osteogenesis and chondrogenesis of primary rabbit periosteal cells under non-uniform 2-axial tensile strain. BioChip J. 14, 438–446 (2020)

    CAS  Article  Google Scholar 

  39. 39.

    Chen, Y., Pasapera, A.M., Koretsky, A.P., Waterman, C.M.: Orientation-specific responses to sustained uniaxial stretching in focal adhesion growth and turnover. Proc. Natl. Acad. Sci. 110, E2352–E2361 (2013)

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  40. 40.

    Chen, X., Fu, X., Shi, J.-G., Wang, H.: Regulation of the osteogenesis of pre-osteoblasts by spatial arrangement of electrospun nanofibers in two-and three-dimensional environments. Nanomed. Nanotechnol. 9, 1283–1292 (2013)

    CAS  Article  Google Scholar 

  41. 41.

    Nakahara, H., Dennis, J.E., Bruder, S.P., Haynesworth, S.E., Lennon, D.P., Caplan, A.I.: In vitro differentiation of bone and hypertrophic cartilage from periosteal-derived cells. Exp. Cell Res. 195, 492–503 (1991)

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  42. 42.

    Kawane, T., Qin, X., Jiang, Q., Miyazaki, T., Komori, H., Yoshida, C.A., dos Santos Matsuura-Kawata, V.K., Sakane, C., Matsuo, Y., Nagai, K.: Runx2 is required for the proliferation of osteoblast progenitors and induces proliferation by regulating Fgfr2 and Fgfr3. Sci. Rep. 8, 1–17 (2018)

    CAS  Article  Google Scholar 

  43. 43.

    Komori, T.: Regulation of proliferation, differentiation and functions of osteoblasts by Runx2. Int. J. Mol. Sci. 20, 1694 (2019)

    CAS  PubMed Central  Article  Google Scholar 

  44. 44.

    Lund, S.A., Giachelli, C.M., Scatena, M.: The role of osteopontin in inflammatory processes. Cell Commun. Signal. 3, 311–322 (2009)

    Article  Google Scholar 

  45. 45.

    Zhu, Y.S., Gu, Y., Jiang, C., Chen, L.: Osteonectin regulates the extracellular matrix mineralization of osteoblasts through P38 signaling pathway. J. Cell. Physiol. 235, 2220–2231 (2020)

    CAS  PubMed  Article  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by Chang Gung Memorial Hospital, Linkou, Taiwan under the projects of CMRPG3H0691 and BMRPC05.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Kin Fong Lei.

Ethics declarations

Conflict of interest

The authors declare that there is no conflict of interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Yang, YC., Hong, QH., Lei, K.F. et al. The Novel Membrane-Type Micro-system to Assess the Bonus Effect of Physiological and Physical Stimuli on Bone Regeneration. BioChip J (2021). https://doi.org/10.1007/s13206-021-00023-2

Download citation

Keywords

  • Periosteal cells
  • Adipose-derived stem cells
  • Osteogenesis
  • Orthopedics
  • Rehabilitation