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Cartilage regeneration using a novel autologous growth factors-based matrix for full-thickness defects in sheep

  • Experimental Study
  • Published:
Knee Surgery, Sports Traumatology, Arthroscopy

Abstract

Purpose

To investigate the chondrogenic-regenerative properties of a novel autologous-made matrix composed of hyaline cartilage chips combined with a growth factors-based clot for full-thickness defects in sheep.

Methods

A full-thickness, 8-mm diameter cartilage defect was created in the weight-bearing area of the medial femoral condyle in 6 sheep. Treatment consisted of surgical implantation of an autologous-based matrix of hyaline cartilage chips combined with a clot of plasma poor in platelets and intraarticular injection of plasma rich in growth factors. Outcome measures at 1, 3 and 6 months included macroscopic International Cartilage Repair Society (ICRS) score, histological and immunohistochemical analysis for collagen expression, and transmission electron microscopy study.

Results

The 6-month macroscopic evaluation showed nearly normal (11.1 ± 0.7) cartilage repair assessment. The ICRS score was significantly higher at 6 months compared to 3 months (5.5 ± 1.3; p < 0.0001) and 1 (1.1 ± 0.4; p < 0.0001) month. At 6 months, hyaline cartilage tissue filling the defect was observed with adequate integration of the regenerated cartilage at the surrounding healthy cartilage margin. At 6 months, mature chondrons and cartilage matrix contained collagen fibers with masked fibrillary structure, and the expression of collagen in the newly formed cartilage was similar in intensity and distribution pattern compared to the healthy adjacent cartilage.

Conclusions

This novel treatment enhanced chondrogenesis and regenerated hyaline cartilage at 6 months with nearly normal macroscopic ICRS assessment. Histological analysis showed equivalent structure to mature cartilage tissue in the defect and a collagen expression pattern in the newly formed cartilage similar to that found in adjacent healthy articular cartilage. The present technique may have clinical application for chondral injuries in humans because this procedure is cheap (no need for allograft, or expensive instrumentation/biomaterials/techniques), easy and fast-performing through a small arthrotomy, and safe (no rejection possibility because the patients’ own tissue, cells, and plasma are used).

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Acknowledgements

The authors are grateful to Dr. Alfonso Blanco Rodríguez, Dra. Montserrat García Balletbó, Dra. Mónica Rubio Zaragoza, Dr. Joaquín Sopena Juncosa for their expert assistance during the development of this study. Also, to Jordi Navarro Lorente for his contributions to the improvement of the matrix preparation, and Sue-Sonia Tizol for her service with language translation.

Funding

This study was supported by the García-Cugat Foundation for Biomedical Research. The authors declare no other sources of funding.

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Authors and Affiliations

  1. Departamento de Medicina y Cirugía Animal, Universidad de Córdoba, Campus Universitario de Rabanales, 14014, Córdoba, Spain

    Juan Manuel Domínguez Pérez, José Andrés Fernández-Sarmiento, Daniel Aguilar García, María del Mar Granados Machuca, Juan Morgaz Rodríguez & Rocío Navarrete Calvo

  2. Fundación García-Cugat, Plaza Alfonso Comín 5-7, 08023, Barcelona, Spain

    Juan Manuel Domínguez Pérez, José Andrés Fernández-Sarmiento, José María Carrillo Poveda, Eduard Alentorn-Geli, Patricia Laiz Boada & Ramón Cugat Bertomeu

  3. Departamento de Anatomía y Anatomía Patológica Comparadas, Universidad de Córdoba, Campus Universitario de Rabanales, 14014, Córdoba, Spain

    José Pérez Arévalo

  4. Departamento de Medicina y Cirugía Animal, Cátedra García Cugat, Universidad CEU Cardenal Herrera, 46115, Valencia, Spain

    José María Carrillo Poveda

  5. Artroscopia GC, SL, Hospital Quirón, Plaza Alfonso Comín 5-7, 08023, Barcelona, Spain

    Eduard Alentorn-Geli, Patricia Laiz Boada & Ramón Cugat Bertomeu

  6. Mutualidad Catalana de Futbolistas, Federación Española de Fútbol, Ronda Sant Pere 17-21, 08010, Barcelona, Spain

    Eduard Alentorn-Geli & Ramón Cugat Bertomeu

Authors
  1. Juan Manuel Domínguez Pérez
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Contributions

Conception and design, or acquisition of data, or analysis and interpretation of data: JMD, AFS, DAG, MMGM, JMR, RNC, JPA, JMCP, EAG, PLB, RCB. Drafting the manuscript or revising it critically for important intellectual content: JMD, AFS, DAG, MMGM, JMR, RNC, JPA, JMCP, EAG, PLB, RCB. Final approval of the version to be published: JMD, AFS, DAG, MMGM, JMR, RNC, JPA, JMCP, EAG, PLB, RCB. Agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: JMD, AFS, DAG, MMGM, JMR, RNC, JPA, JMCP, EAG, PLB, RCB.

Corresponding author

Correspondence to Juan Manuel Domínguez Pérez.

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Conflict of interest

The authors declare that there is no conflict of interest regarding the publication of this article. The authors do not have any financial interest or other relationship with any commercial company related to this study.

Ethical approval

Authorization of the Junta de Andalucia bioethics committee number 12/06/2016/109—reference SSA/SIS/MD/jv.

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Domínguez Pérez, J.M., Fernández-Sarmiento, J.A., Aguilar García, D. et al. Cartilage regeneration using a novel autologous growth factors-based matrix for full-thickness defects in sheep. Knee Surg Sports Traumatol Arthrosc 27, 950–961 (2019). https://doi.org/10.1007/s00167-018-5107-z

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  • DOI: https://doi.org/10.1007/s00167-018-5107-z

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