Journal of Orthopaedic Surgery and Research (Feb 2019)

Combined ascorbic acid and T3 produce better healing compared to bone marrow mesenchymal stem cells in an Achilles tendon injury rat model: a proof of concept study

  • Francesco Oliva,
  • Nicola Maffulli,
  • Clarissa Gissi,
  • Francesca Veronesi,
  • Lucia Calciano,
  • Milena Fini,
  • Silvia Brogini,
  • Marialucia Gallorini,
  • Cristina Antonetti Lamorgese Passeri,
  • Roberta Bernardini,
  • Rosella Cicconi,
  • Maurizio Mattei,
  • Anna Concetta Berardi

DOI
https://doi.org/10.1186/s13018-019-1098-9
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 10

Abstract

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Abstract Background This pilot study aimed to ascertain whether the local application of ascorbic acid (AA), of T3, and of rat (r) bone marrow mesenchymal stem cells (BMSCs), alone or in all possible combinations, promoted healing after an Achilles tendon injury in a rat model. Methods An Achilles tendon defect was produced in 24 6–8-week-old male inbred Lewis rats. The animals were then randomly divided into eight groups of three rats each. The tendon defect was filled with 50 μL of phosphate-buffered saline (PBS) containing (1) 50 μg/mL AA (AA group), (2) 10−7 M T3 (T3 group), (3) 4 × 106 rBMSCs (rBMSC group), (4) 50 μg/mL AA + 10−7 M T3 (AA + T3 group), (5) 4 × 106 rBMSCs + 50 μg/mL AA (rBMSC + AA group), (6) 4 × 106 rBMSCs + 10−7 M T3 (rBMSC + T3 group), (7) 4 × 106 rBMSCS + 50 μg/mL AA + 10−7 M T3 (rBMSC + AA + T3 group), and (8) PBS only (control group: CTRL). All treatments were administered by local injection immediately after the tendons had been damaged; additionally, AA was injected also on the second and fourth day from the first injection (for groups 1, 4, 5, and 7), and T3 was injected again every day for 4 days (for groups 2, 4, 6, and 7). At 30 days from initial treatment, tendon samples were harvested, and the quality of tendon repair was evaluated using histological and histomorphological analysis. The structure and morphology of the injured Achilles tendons were evaluated using the modified Svensson, Soslowsky, and Cook score, and the collagen type I and III ratio was calculated. Results The group treated with AA combined with T3 displayed the lowest Svensson, Soslowsky, and Cook total score value of all tissue sections at histopathological examination, with fiber structure close to regular orientation, normal-like tendon vasculature, and no cartilage formation. AA + T3 also showed the highest collagen I and the lowest collagen III values compared to all other treatments including the CTRL. Conclusion There are potential benefits using a combination of AA and T3 to accelerate tendon healing.

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