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Novel alginate biphasic scaffold for osteochondral regeneration: an in vivo evaluation in rabbit and sheep models

  • Tissue Engineering Constructs and Cell Substrates
  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

Current therapeutic strategies for osteochondral restoration showed a limited regenerative potential. In fact, to promote the growth of articular cartilage and subchondral bone is a real challenge, due to the different functional and anatomical properties. To this purpose, alginate is a promising biomaterial for a scaffold-based approach, claiming optimal biocompatibility and good chondrogenic potential. A previously developed mineralized alginate scaffold was investigated in terms of the ability to support osteochondral regeneration both in a large and medium size animal model. The results were evaluated macroscopically and by microtomography, histology, histomorphometry, and immunohistochemical analysis. No evidence of adverse or inflammatory reactions was observed in both models, but limited subchondral bone formation was present, together with a slow scaffold resorption time.

The implantation of this biphasic alginate scaffold provided partial osteochondral regeneration in the animal model. Further studies are needed to evaluate possible improvement in terms of osteochondral tissue regeneration for this biomaterial.

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References

  1. Gomoll AH, Filardo G, de Girolamo L, et al. Surgical treatment for early osteoarthritis. Part I: cartilage repair procedures. Knee Surg Sports Traumatol Arthrosc. 2012;20:450–66.

    Article  CAS  Google Scholar 

  2. Gomoll AH, Filardo G, Almqvist FK, et al. Surgical treatment for early osteoarthritis. Part II: allografts and concurrent procedures. Knee Surg Sports Traumatol Arthrosc. 2012;20:468–86.

    Article  CAS  Google Scholar 

  3. Filardo G, Kon E, Di Martino A, et al. Is the clinical outcome after cartilage treatment affected by subchondral bone edema? Knee Surg Sports Traumatol Arthrosc. 2014;22:1337–44.

    Article  Google Scholar 

  4. Kon E, Roffi A, Filardo G, et al. Scaffold-based cartilage treatments: with or without cells? A systematic review of preclinical and clinical evidence. Arthroscopy. 2015;31:767–75.

    Article  Google Scholar 

  5. Abarrategi A, Lópiz-Morales Y, Ramos V, et al. Chitosan scaffolds for osteochondral tissue regeneration. J Biomed Mater Res A. 2010;95:1132–41.

    Article  Google Scholar 

  6. Amadori S, Torricelli P, Panzavolta S, et al. Multi-layered scaffolds for osteochondral tissue engineering: in vitro response of co-cultured human mesenchymal stem cells. Macromol Biosci. 2015;15:1535–45.

    Article  CAS  Google Scholar 

  7. Tampieri A, Sandri M, Landi E, et al. Design of graded biomimetic osteochondral composite scaffolds. Biomaterials. 2008;29:3539–46.

    Article  CAS  Google Scholar 

  8. Filardo G, Kon E, Perdisa F, et al. Osteochondral scaffold reconstruction for complex knee lesions: a comparative evaluation. Knee. 2013;20:570.

    Article  CAS  Google Scholar 

  9. Marcacci M, Zaffagnini S, Kon E, et al. Unicompartmental osteoarthritis: an integrated biomechanical and biological approach as alternative to metal resurfacing. Knee Surg Sports Traumatol Arthrosc. 2013;21:2509–17.

    Article  CAS  Google Scholar 

  10. Kon E, Filardo G, Di Martino A, et al. Clinical results and MRI evolution of a nano-composite multilayered biomaterial for osteochondral regeneration at 5 years. Am J Sports Med. 2014;42:158–65.

    Article  Google Scholar 

  11. Häuselmann HJ, Masuda K, Hunziker EB, et al. Adult human chondrocytes cultured in alginate form a matrix similar to native human articular cartilage. Am J Physiol. 1996;71:C742–52.

    Article  Google Scholar 

  12. Miralles G, Baudoin R, Dumas D, et al. Sodium alginate sponges with or withoutsodium hyaluronate: in vitro engineering of cartilage. J Biomed Mater Res. 2001;57:268–78.

    Article  CAS  Google Scholar 

  13. Park Y, Sugimoto M, Watrin A, et al. BMP-2 induces the expression of chondrocyte-specific genes in bovine synovium-derived progenitor cells cultured in three-dimensional alginate hydrogel. Osteoarthr Cartil. 2005;13:527–36.

    Article  CAS  Google Scholar 

  14. Genes NG, Rowley JA, Mooney DJ, et al. Effect of substrate mechanics on chondrocyte adhesion to modified alginate surfaces. Arch Biochem Biophys. 2004;422:161–67.

    Article  CAS  Google Scholar 

  15. Ma K, Titan AL, Stafford M, et al. Variations in chondrogenesis of human bone marrow-derived mesenchymal stem cells in fibrin/alginate blended hydrogels. Acta Biomater. 2012;8:3754–64.

    Article  CAS  Google Scholar 

  16. Guo JF, Jourdian GW, MacCallum DK. Culture and growth characteristics of chondrocytes encapsulated in alginate beads. Connect Tissue Res. 1989;19:277–97.

    Article  CAS  Google Scholar 

  17. Diduch DR, Jordan LC, Mierisch CM, et al. Marrow stromal cells embedded in alginate for repair of osteochondral defects. Arthroscopy. 2000;16:571–77.

    Article  CAS  Google Scholar 

  18. Ko HF, Sfeir C, Kumta PN. Novel synthesis strategies for natural polymer and composite biomaterials as potential scaffolds for tissue engineering. Philos Trans A Math Phys Eng Sci. 2010;368:1981–97.

    Article  CAS  Google Scholar 

  19. Kumar A, Akkineni AR, Basu B, et al. Three-dimensional plotted hydroxyapatite scaffolds with predefined architecture: comparison of stabilization by alginate cross-linking versus sintering. J Biomater Appl. 2016;30:1168–81.

    Article  CAS  Google Scholar 

  20. Schütz K, Despang F, Lode A, Gelinsky M. Cell-laden biphasic scaffolds with anisotropic structure for the regeneration of osteochondral tissue. J Tissue Eng Regen Med. 2016;10:404–17.

    Article  Google Scholar 

  21. Fortier LA, Mohammed HO, Lust G, Nixon AJ. Insulin-like growth factor-I enhances cell-based repair of articular cartilage. J Bone Jt Surg Br. 2002;84:276–88.

    Article  CAS  Google Scholar 

  22. Niederauer GG, Slivka MA, Leatherbury NC, et al. Evaluation of multiphase implants for repair of focal osteochondral defects in goats. Biomaterials. 2000;21:2561–74.

    Article  CAS  Google Scholar 

  23. Paul K, Lee BY, Abueva C, et al. In vivo evaluation of injectable calcium phosphate cement composed of Zn and Si-incorporated β-tricalcium phosphate and monocalcium phosphate monohydrate for a critical sized defect of the rabbit femoral condyle. J Biomed Mater Res B Appl Biomater. 2015. https://doi.org/10.1002/jbm.b.33537

    Article  Google Scholar 

  24. Pineda S, Pollack A, Stevenson S, et al. A semiquantitative scale for histologic grading of articular cartilage repair. Acta Anat. 1992;143:335–40.

    Article  CAS  Google Scholar 

  25. Venkatesan J, Kim SK. Chitosan composites for bone tissue engineering—an overview. Drugs. 2010;8:2252–66.

    CAS  Google Scholar 

  26. Hoemann C, Hurtig M, Rossomacha E, et al. Chitosan glycerol phosphate/blood implants improve hyaline cartilage repair in ovine microfracture defects. J Bone Jt Surg Am. 2005;87:2671–86.

    Article  Google Scholar 

  27. Martini L, Fini M, Giavaresi G, Giardino R. Sheep model in orthopedic research: a literature review. Comp Med. 2001;51:292–99.

    CAS  Google Scholar 

  28. Brehm W, Aklin B, Yamashita T, et al. Repair of superficial osteochondral defects with an autologous scaffold-free cartilage construct in a caprine model: implantation method and short-term results. Osteoarthr Cartil. 2006;14:1214.

    Article  CAS  Google Scholar 

  29. Buma P, Schreurs W, Verdonschot N. Skeletal tissue engineering-from in vitro studies to large animal models. Biomaterials. 2004;25:1487–95.

    Article  CAS  Google Scholar 

  30. Gelinsky M, Eckert M. and Despang F. Biphasic, but monolithic scaffolds for the therapy of osteochondral defects. Int JMater Res. 2007;98:749–55.

    Article  CAS  Google Scholar 

  31. Bernhardt A, Despang F, Lode A, et al. Proliferation and osteogenic differentiation of human bone marrow stromal cells on alginate-gelatine-hydroxyapatite scaffolds with anisotropic pore structure. J Tissue Eng Regen Med. 2009;3:54–62.

    Article  CAS  Google Scholar 

  32. Park H, Lee KY. Cartilage regeneration using biodegradable oxidized alginate/hyaluronate hydrogels. J Biomed Mater Res A. 2014;102:4519–25.

    Article  Google Scholar 

  33. Leddy HA, Awad HA, Guilak F. Molecular diffusion in tissue-engineered cartilage constructs: effects of scaffold material, time, and culture conditions. J Biomed Mater Res B Appl Biomater. 2004;70:397–406.

    Article  Google Scholar 

  34. Perka C, Spitzer RS, Lindenhayn K, et al. Matrix-mixed culture: new methodology for chondrocyte culture and preparation of cartilage transplants. J Biomed Mater Res. 2000;49:305–11.

    Article  CAS  Google Scholar 

  35. Filardo G, Perdisa F, Roffi A, et al. Stem cells in articular cartilage regeneration. J Orthop Surg Res. 2016;11:42.

    Article  Google Scholar 

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Acknowledgements

This study was supported by European Project OPHIS-COMPOSITE PHENOTYPIC TRIGGERS FOR BONE AND CARTILAGE REPAIR (FP7-NMP-2009-SMALL 3-246373).

Author contributions

GF: conception and design of the study, animal surgery, manuscript drafting. FP: collaboration for animal surgery, macroscopic evaluations, manuscript drafting. MG: scaffold development and production, manuscript drafting. MF: manuscript drafting, analysis and interpretation of the data, final approval of the article. FD: scaffold development and production, manuscript drafting. MM: senior scientific consultant, critical revision of the article. APP: microtomography analysis. AR: logistic support, assembly of the data, manuscript drafting. FS: histological and histomorphometric analysis on sheep. MS: histological analysis on rabbits. KS: scaffold development and production, manuscript drafting. EK: obtaining of funding, conception and design of the study, animal surgery, final approval of the article

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Authors and Affiliations

  1. Nano-Biotechnology (NABI) Laboratory, Rizzoli RIT Department, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, Bologna, 40136, Italy

    Giuseppe Filardo, Francesco Perdisa & Alice Roffi

  2. Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital and Faculty of Medicine, Technische Universität Dresden, Fetscherstr. 73, Dresden, 01307, Germany

    Michael Gelinsky, Florian Despang & Kathleen Schütz

  3. Laboratory of Biocompatibility, Innovative Technologies and Advanced Therapies, Rizzoli RIT Department, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, Bologna, 40136, Italy

    Milena Fini, Anna Paola Parrilli, Francesca Salamanna & Maria Sartori

  4. Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, Bologna, 40136, Italy

    Milena Fini

  5. Knee Joint Reconstruction Center - 3rd Orthopaedic Division, Humanitas Clinical Institute, Via Alessandro Manzoni 56, Rozzano, Milan, Italy

    Maurilio Marcacci & Elizaveta Kon

  6. Department of Biomedical Sciences, Humanitas University, Via Manzoni 113, Rozzano, Milan, Italy

    Maurilio Marcacci & Elizaveta Kon

Authors
  1. Giuseppe Filardo
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  2. Francesco Perdisa
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  3. Michael Gelinsky
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  4. Florian Despang
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  5. Milena Fini
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  6. Maurilio Marcacci
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  7. Anna Paola Parrilli
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  8. Alice Roffi
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  9. Francesca Salamanna
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  10. Maria Sartori
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  11. Kathleen Schütz
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  12. Elizaveta Kon
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Corresponding author

Correspondence to Francesco Perdisa.

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Conflict of interest

GF is consultant for: Finceramica Faenza S.p.A, Italy; Fidia farmaceutica, Italy; CartiHeal ltd (2009) Israel, EON Medica, Italy. MM receives royalties from Finceramica Faenza S.p.A., Italy. EK is consultant for Finceramica Faenza S.p.A., Italy; CartiHeal (2009) ltd, Israel. GF, EK, MM receive Institutional Support from FinCeramica Faenza S.p.A.; Fidia farmaceutica, Italy, IGEA Biomedical, Italy, Zimmer-BIOMET, USA, Kensey Nash, USA. The remaing authors declare that they have no conflict of interest.

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Filardo, G., Perdisa, F., Gelinsky, M. et al. Novel alginate biphasic scaffold for osteochondral regeneration: an in vivo evaluation in rabbit and sheep models. J Mater Sci: Mater Med 29, 74 (2018). https://doi.org/10.1007/s10856-018-6074-0

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  • DOI: https://doi.org/10.1007/s10856-018-6074-0

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