Skip to main content
SpringerLink
Log in

Polycaprolactone Triol–Citrate Scaffolds Enriched with Human Platelet Releasates Promote Chondrogenic Phenotype and Cartilage Extracellular Matrix Formation

  • Original Article
  • Published:
Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

In this paper we report the differentiating properties of platelet-rich plasma releasates (PRPr) on human chondrocytes within elastomeric polycaprolactone triol–citrate (PCLT–CA) porous scaffold. Human-derived chondrocyte cellular content of glycosaminoglycans (GAGs) and total collagen were determined after seeding into PCLT–CA scaffold enriched with PRPr cells. Immunostaining and real time PCR was applied to evaluate the expression levels of chondrogenic and extracellular gene markers. Seeding of chondrocytes into PCLT–CA scaffold enriched with PRPr showed significant increase in total collagen and GAGs production compared with chondrocytes grown within control scaffold without PRPr cells. The mRNA levels of collagen II and SOX9 increased significantly while the upregulation in Cartilage Oligomeric Matrix Protein (COMP) expression was statistically insignificant. We also report the reduction of the expression levels of collagen I and III in chondrocytes as a consequence of proximity to PRPr cells within the scaffold. Interestingly, the pre-loading of PRPr caused an increase of expression levels of following extracellular matrix (ECM) proteins: fibronectin, laminin and integrin β over the period of 3 days. Overall, our results introduce the PCLT–CA elastomeric scaffold as a new system for cartilage tissue engineering. The method of PRPr cells loading prior to chondrocyte culture could be considered as a potential environment for cartilage tissue engineering as the differentiation and ECM formation is enhanced significantly.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Snyder TN, Madhavan K, Intrator M, Dregalla RC, Park D. A fibrin/hyaluronic acid hydrogel for the delivery of mesenchymal stem cells and potential for articular cartilage repair. J Biol Eng. 2014;8:10.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Sandell LJ, Aigner T. Articular cartilage and changes in arthritis. An introduction: Cell biology of osteoarthritis. Arthritis Res. 2001;3:107–13.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Mobasheri A, Kalamegam G, Musumeci G, Batt ME. Chondrocyte and mesenchymal stem cell-based therapies for cartilage repair in osteoarthritis and related orthopaedic conditions. Maturitas. 2014;78:188–98.

    Article  PubMed  CAS  Google Scholar 

  4. Kang Y, Yang J, Khan S, Anissian L, Ameer GA. A new biodegradable polyester elastomer for cartilage tissue engineering. J Biomed Mater Res Part A. 2006;77:331–9.

    Article  CAS  Google Scholar 

  5. Hildner F, Albrecht C, Gabriel C, Redl H, Van Griensven M. State of the art and future perspectives of articular cartilage regeneration: a focus on adipose-derived stem cells and platelet-derived products. J Tissue Eng Regen Med. 2011;5:e36–51.

    Article  PubMed  CAS  Google Scholar 

  6. Hao T, Wen N, Cao JK, Wang HB, Lu SH, Liu T, et al. The support of matrix accumulation and the promotion of sheep articular cartilage defects repair in vivo by chitosan hydrogels. Osteoarthr Cartil. 2010;18:257–65.

    Article  PubMed  CAS  Google Scholar 

  7. Whitaker MJ, Quirk RA, Howdle SM, Shakesheff KM. Growth factor release from tissue engineering scaffolds. J Pharm Pharmacol. 2001;53:1427–37.

    Article  PubMed  CAS  Google Scholar 

  8. Diaz-Gomez L, Alvarez-Lorenzo C, Concheiro A, Silva M, Dominguez F, Sheikh FA, et al. Biodegradable electrospun nanofibers coated with platelet-rich plasma for cell adhesion and proliferation. Mater Sci Eng C. 2014;40:180–8.

    Article  CAS  Google Scholar 

  9. Shimojo AA, Perez AG, Galdames SE, Brissac IC, Santana MH. Stabilization of porous chitosan improves the performance of its association with platelet-rich plasma as a composite scaffold. Mater Sci Eng C. 2016;60:538–46.

    Article  CAS  Google Scholar 

  10. Foster TE, Puskas BL, Mandelbaum BR, Gerhardt MB, Rodeo SA. Platelet-rich plasma: from basic science to clinical applications. Am J Sports Med. 2009;37:2259–72.

    Article  PubMed  Google Scholar 

  11. Demidova-Rice TN, Hamblin MR, Herman IM. Acute and impaired wound healing: pathophysiology and current methods for drug delivery, part 2: role of growth factors in normal and pathological wound healing: therapeutic potential and methods of delivery. Adv Skin Wound Care. 2012;25:349–70.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Tran RT, Yang J, Ameer GA. Citrate-based biomaterials and their applications in regenerative engineering. Annu Rev Mater Res. 2015;45:277–310.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Shirazi HS, Forooshani PK, Pingguan-Murphy B, Djordjevic, I. Processing and characterization of elastomeric polycaprolactone triol–citrate coatings for biomedical applications. Prog Org Coat. 2014;77:821–9.

    Article  CAS  Google Scholar 

  14. Rothan HA, Djordjevic I, Bahrani H, Paydar M, Ibrahim F, Abd Rahmanh N, et al. Three-dimensional culture environment increases the efficacy of platelet rich plasma releasate in prompting skin fibroblast differentiation and extracellular matrix formation. Int J Med Sci. 2014;11:1029–38.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Caron MM, Emans PJ, Coolsen MM, Voss L, Surtel DA, Cremers A, et al. Redifferentiation of dedifferentiated human articular chondrocytes: Comparison of 2D and 3D cultures. Osteoarthr Cartil. 2012;20:1170–8.

    Article  PubMed  CAS  Google Scholar 

  16. Lin L, Shen Q, Xue T, Duan X, Fu X, Yu C. Sonic hedgehog improves redifferentiation of dedifferentiated chondrocytes for articular cartilage repair. PLoS One. 2014;9:e88550.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Xu F, Xu L, Wang Q, Ye Z, Zhou Y, Tan WS. 3D dynamic culture of rabbit articular chondrocytes encapsulated in alginate gel beads using spinner flasks for cartilage tissue regeneration. BioMed Res Int. 2014;2014:539789.

    PubMed  PubMed Central  Google Scholar 

  18. Bernardini G, Chellini F, Frediani B, Spreafico A, Santucci A. Human platelet releasates combined with polyglycolic acid scaffold promote chondrocyte differentiation and phenotypic maintenance. J Biosci. 2015;40:61–9.

    Article  PubMed  CAS  Google Scholar 

  19. Gigout A, Jolicoeur M, Buschmann MD. Low calcium levels in serum-free media maintain chondrocyte phenotype in monolayer culture and reduce chondrocyte aggregation in suspension culture. Osteoarthr Cartil. 2005;13:1012–24.

    Article  PubMed  CAS  Google Scholar 

  20. Yates KE, Allemann F, Glowacki J. Phenotypic analysis of bovine chondrocytes cultured in 3D collagen sponges: effect of serum substitutes. Cell Tissue Bank. 2005;6:45–54.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Tseng S, Reddi AH, Di Cesare PE. Cartilage oligomeric matrix protein (COMP): A biomarker of arthritis. Biomark Insights. 2009;4:33–44.

    PubMed  PubMed Central  CAS  Google Scholar 

  22. Hamid AA, Idrus RB, Saim AB, Sathappan S, Chua KH. Characterization of human adipose-derived stem cells and expression of chondrogenic genes during induction of cartilage differentiation. Clinics. 2012;67:099–106.

    Article  Google Scholar 

  23. Tavella S, Bellese G, Castagnola P, Martin I, Piccini D, Doliana R, et al. Regulated expression of fibronectin, laminin and related integrin receptors during the early chondrocyte differentiation. J Cell Sci. 1997;110:2261–70.

    PubMed  CAS  Google Scholar 

  24. Fukumoto T, Sanyal A, Fitzsimmons JS, O'Driscoll SW. Expression of β1 integrins during periosteal chondrogenesis. Osteoarthr Cartil. 2002;10:135–44.

    Article  PubMed  CAS  Google Scholar 

  25. Knudson W, Loeser RF. CD44 and integrin matrix receptors participate in cartilage homeostasis. Cell Mol Life Sci. 2002;59:36–44.

    Article  PubMed  CAS  Google Scholar 

  26. Sophia Fox AJ, Bedi A, Rodeo SA. The basic science of articular cartilage: structure, composition, and function. Sports Health A Multidiscip Approach. 2009;1:461–8.

    Article  Google Scholar 

  27. Qiu H, Yang J, Kodali P, Koh J, Ameer GA. A citric acid-based hydroxyapatite composite for orthopedic implants. Biomaterials. 2006;27:5845–54.

    Article  PubMed  CAS  Google Scholar 

  28. Mirza EH, Pan-Pan C, Ibrahim W, Bin WMA, Djordjevic I, Pingguan-Murphy B. Chondroprotective effect of zinc oxide nanoparticles in conjunction with hypoxia on bovine cartilage-matrix synthesis. J Biomed Mater Res A. 2015;103:3554–63.

    Article  PubMed  CAS  Google Scholar 

  29. Zeimaran E, Pourshahrestani S, Pingguan-Murphy B, Kadri NA, Rothan HA, Yusof R, et al. Fabrication and characterization of poly(octanediol citrate)/gallium-containing bioglass microcomposite scaffolds. J Mater Sci. 2015;50:2189–201.

    Article  CAS  Google Scholar 

Download references

Acknowledgement

This project was funded by University of Malaya-Malaysia (RG377-15AFR).

Author information

Authors and Affiliations

  1. Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Hussin A. Rothan & Rohana Yusof

  2. Department of Orthopedic Surgery, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Suhaeb A. Mahmod & Simmrat Snigh

  3. School of Materials Science and Engineering, Nanyang Technological University, Singapore, 639798, Singapore

    Ivan Djordjevic

  4. Department of Medicine, Faculty of Medicine, University of Kebangsaan Malaysia, 56000, Cheras, Kuala Lumpur, Malaysia

    Mojtaba Golpich

Authors
  1. Hussin A. Rothan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Suhaeb A. Mahmod
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ivan Djordjevic
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mojtaba Golpich
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rohana Yusof
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Simmrat Snigh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hussin A. Rothan.

Ethics declarations

Conflict of interest

We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.

Ethical statement

This study was approved by the Medical Ethics Committee, Faculty of Medicine University of Malaya (DFOP 1213/0079 (L)).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rothan, H.A., Mahmod, S.A., Djordjevic, I. et al. Polycaprolactone Triol–Citrate Scaffolds Enriched with Human Platelet Releasates Promote Chondrogenic Phenotype and Cartilage Extracellular Matrix Formation. Tissue Eng Regen Med 14, 93–101 (2017). https://doi.org/10.1007/s13770-017-0023-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13770-017-0023-8

Keywords

Search

Navigation