Display options
Cite
Quang Le B, Van Blitterswijk C, De Boer J. An Approach to In Vitro Manufacturing of Hypertrophic Cartilage Matrix for Bone Repair. Bioengineering (Basel). 2017;4(2)doi: 10.3390/bioengineering4020035.
Quang Le, B., Van Blitterswijk, C., & De Boer, J. (2017). An Approach to In Vitro Manufacturing of Hypertrophic Cartilage Matrix for Bone Repair. Bioengineering (Basel, Switzerland), 4(2), . https://doi.org/10.3390/bioengineering4020035
Quang Le, Bach, et al. "An Approach to In Vitro Manufacturing of Hypertrophic Cartilage Matrix for Bone Repair." Bioengineering (Basel, Switzerland) vol. 4,2 (2017). doi: https://doi.org/10.3390/bioengineering4020035
Quang Le B, Van Blitterswijk C, De Boer J. An Approach to In Vitro Manufacturing of Hypertrophic Cartilage Matrix for Bone Repair. Bioengineering (Basel). 2017 Apr 20;4(2). doi: 10.3390/bioengineering4020035. PMID: 28952514; PMCID: PMC5590482.
Copy Download .nbib Format: NLM
Share it on

Bioengineering (Basel). 2017 Apr 20;4(2). doi: 10.3390/bioengineering4020035.

An Approach to In Vitro Manufacturing of Hypertrophic Cartilage Matrix for Bone Repair.

Bioengineering (Basel, Switzerland)

Bach Quang Le, Clemens Van Blitterswijk, Jan De Boer

Affiliations

  1. Department of Tissue Regeneration, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Postbus 217, 7500 AE Enschede, The Netherlands. [email protected].
  2. Department of Tissue Regeneration, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Postbus 217, 7500 AE Enschede, The Netherlands. [email protected].
  3. Department of Complex Tissue Regeneration, MERLN Institute, University of Maastricht, P.O. Box 616, 6200 MD Maastricht, The Netherlands. [email protected].
  4. Department of Tissue Regeneration, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Postbus 217, 7500 AE Enschede, The Netherlands. [email protected].
  5. Laboratory for Cell Biology-inspired Tissue Engineering, MERLN Institute, University of Maastricht, P.O. Box 616, 6200 MD Maastricht, The Netherlands. [email protected].

PMID: 28952514 PMCID: PMC5590482 DOI: 10.3390/bioengineering4020035

Abstract

Devitalized hypertrophic cartilage matrix (DCM) is an attractive concept for an off-the-shelf bone graft substitute. Upon implantation, DCM can trigger the natural endochondral ossification process, but only when the hypertrophic cartilage matrix has been reconstituted correctly. In vivo hypertrophic differentiation has been reported for multiple cell types but up-scaling and in vivo devitalization remain a big challenge. To this end, we developed a micro tissue-engineered cartilage (MiTEC) model using the chondrogenic cell line ATDC5. Micro-aggregates of ATDC5 cells (approximately 1000 cells per aggregate) were cultured on a 3% agarose mold consisting of 1585 microwells, each measuring 400 µm in diameter. Chondrogenic differentiation was strongly enhanced using media supplemented with combinations of growth factors e.g., insulin, transforming growth factor beta and dexamethasone. Next, mineralization was induced by supplying the culture medium with beta-glycerophosphate, and finally we boosted the secretion of proangiogenic growth factors using the hypoxia mimetic phenanthroline in the final stage of in vivo culture. Then, ATDC5 aggregates were devitalized by freeze/thawing or sodium dodecyl sulfate treatment before co-culturing with human mesenchymal stromal cells (hMSCs). We observed a strong effect on chondrogenic differentiation of hMSCs. Using this MiTEC model, we were able to not only upscale the production of cartilage to a clinically relevant amount but were also able to vary the cartilage matrix composition in different ways, making MiTEC an ideal model to develop DCM as a bone graft substitute.

Keywords: Hypertrophic cartilage, ATDC5, decellularized matrix, devitalized matrix, tissue engineering, bone regeneration

References

  1. J Biomed Mater Res A. 2012 Sep;100(9):2507-16 - PubMed
  2. Tissue Eng Part A. 2012 Jul;18(13-14):1334-43 - PubMed
  3. J Biomech. 2010 Jan 5;43(1):55-62 - PubMed
  4. Tissue Eng Part A. 2008 Jan;14(1):135-47 - PubMed
  5. J Bone Miner Res. 2014;29(5):1269-82 - PubMed
  6. J Postgrad Med. 2002 Apr-Jun;48(2):142-8 - PubMed
  7. Proc Natl Acad Sci U S A. 2014 Dec 9;111(49):17426-31 - PubMed
  8. Science. 1965 Nov 12;150(3698):893-9 - PubMed
  9. Mech Dev. 1999 Sep;87(1-2):57-66 - PubMed
  10. Eur Cell Mater. 2008 Apr 01;15:53-76 - PubMed
  11. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2012 Oct;29(5):1007-13 - PubMed
  12. Acta Biomater. 2014 Jul;10(7):3254-63 - PubMed
  13. Biomaterials. 2012 Apr;33(11):3205-15 - PubMed
  14. Osteoarthritis Cartilage. 2013 Apr;21(4):604-13 - PubMed
  15. Tissue Eng Part B Rev. 2010 Aug;16(4):385-95 - PubMed
  16. J Orthop Res. 2007 Aug;25(8):1029-41 - PubMed
  17. J Periodontol. 1997 Nov;68(11):1076-84 - PubMed
  18. Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7251-6 - PubMed
  19. Biomaterials. 2011 Apr;32(12):3233-43 - PubMed
  20. Orthop Surg. 2014 Aug;6(3):171-8 - PubMed
  21. J Bone Joint Surg Am. 1952 Apr;34-A(2):443-76 - PubMed
  22. Proc Natl Acad Sci U S A. 2008 May 13;105(19):6840-5 - PubMed
  23. Ann Biomed Eng. 2014 Feb;42(2):432-44 - PubMed
  24. J Anat. 1958 Jan;92(1):28-38 - PubMed
  25. J Cell Biochem. 2003 Apr 1;88(5):873-84 - PubMed
  26. Spine (Phila Pa 1976). 2006 May 20;31(12):1299-306; discussion 1307-8 - PubMed
  27. Int J Oral Maxillofac Implants. 2012 Nov-Dec;27(6):1400-8 - PubMed
  28. Injury. 2011 Jun;42(6):551-5 - PubMed
  29. Int J Oral Sci. 2012 Jun;4(2):64-8 - PubMed
  30. Nat Rev Rheumatol. 2015 Jan;11(1):45-54 - PubMed
  31. Proc Natl Acad Sci U S A. 2012 May 1;109(18):6886-91 - PubMed
  32. J Cell Biochem. 2013 Jun;114(6):1223-9 - PubMed
  33. Tissue Eng. 1998 Winter;4(4):415-28 - PubMed
  34. Tissue Eng Part A. 2013 Apr;19(7-8):928-37 - PubMed
  35. Development. 2017 Jan 15;144(2):221-234 - PubMed
  36. BMC Musculoskelet Disord. 2011 Jan 31;12:31 - PubMed
  37. J Bone Joint Surg Am. 2001;83-A Suppl 2 Pt 2:98-103 - PubMed
  38. J Orthop Trauma. 2010 Mar;24 Suppl 1:S36-40 - PubMed
  39. Surgeon. 2012 Aug;10(4):230-9 - PubMed
  40. J Biomed Mater Res A. 2014 Aug;102(8):2875-83 - PubMed
  41. Springerplus. 2013 Jul 05;2(1):303 - PubMed
  42. Trends Biotechnol. 2013 Feb;31(2):108-15 - PubMed
  43. Biomaterials. 2013 Apr;34(12):3053-63 - PubMed
  44. J Dent Res. 2007 Oct;86(10):937-50 - PubMed
  45. Transl Res. 2014 Apr;163(4):268-85 - PubMed
  46. Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):3997-4002 - PubMed
  47. Nature. 2003 May 15;423(6937):332-6 - PubMed
  48. J Bone Joint Surg Br. 1965 May;47:304-18 - PubMed
  49. Acta Biomater. 2015 Sep;23 :82-90 - PubMed
  50. J Biomed Mater Res A. 2011 Nov;99(2):283-94 - PubMed
  51. Surgeon. 2013 Feb;11(1):39-48 - PubMed
  52. J Bone Joint Surg Br. 1968 Feb;50(1):198-215 - PubMed
  53. Eur Cell Mater. 2006 Nov 09;12:64-9; discussion 69-70 - PubMed
  54. Clin Orthop Relat Res. 1998 Oct;(355 Suppl):S7-21 - PubMed

Publication Types