Combined therapy of platelet-rich plasma and basic fibroblast growth factor using gelatin-hydrogel sheet for rotator cuff healing in rat models.

Takeshi Kataoka, Yutaka Mifune, Atsuyuki Inui, Hanako Nishimoto, Takashi Kurosawa, Kohei Yamaura, Shintaro Mukohara, Takehiko Matsushita, Takahiro Niikura, Yasuhiko Tabata, Ryosuke Kuroda
Author Information
  1. Takeshi Kataoka: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan. t.kataoka1010@gmail.com. ORCID
  2. Yutaka Mifune: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
  3. Atsuyuki Inui: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
  4. Hanako Nishimoto: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
  5. Takashi Kurosawa: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
  6. Kohei Yamaura: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
  7. Shintaro Mukohara: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
  8. Takehiko Matsushita: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
  9. Takahiro Niikura: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
  10. Yasuhiko Tabata: Laboratory of Biomaterials, Institute for Frontier Life and Medical Sciences, Kyoto University, 53 Kawara-cho Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
  11. Ryosuke Kuroda: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.

Abstract

INTRODUCTION: Excellent outcomes of arthroscopic rotator cuff repair for small and medium tears have been recently reported. However, re-tears after surgery have been a common complication after surgical repair of large and massive rotator cuff tears and often occur in early postoperative phase. It was previously reported that basic fibroblast growth factor and platelet-rich plasma enhanced rotator cuff tear healing. We hypothesized that this combined therapy could enhance rotator cuff healing after rotator cuff repair in a rat model. This study aimed to evaluate the efficacy of combined therapy of platelet-rich plasma and basic fibroblast growth factor with gelatin-hydrogel sheet.
METHODS: To create a rotator cuff defect, the infraspinatus tendon of Sprague Dawley rat was resected from the greater tuberosity. The infraspinatus tendons were repaired and covered with gelatin-hydrogel sheet impregnated with PBS (control group), basic fibroblast growth factor (bFGF group), platelet-rich plasma (PRP group), or both basic fibroblast growth factor and platelet-rich plasma (combined group). Histological examinations were conducted using hematoxylin and eosin, safranin O, and immunofluorescence staining, such as Isolectin B4, type II collagen at 2 weeks postoperatively. For mechanical analysis, ultimate failure load of the tendon-humeral head complex was evaluated at 6 weeks postoperatively.
RESULTS: In the hematoxylin and eosin staining, the tendon maturing score of the combined group was higher than that of the control group at postoperative 2 weeks. In the safranin O staining, stronger proteoglycan staining was observed in the combined group compared with the other groups at postoperative 2 weeks. Vascular staining with isolectin B4 in 3 treatment groups was significantly higher than that in the control group. Type II collagen expression in the combined group was significantly higher than those in the other groups. The ultimate failure load of the combined group was significantly higher than that of the control group.
CONCLUSION: Combined therapy of basic fibroblast growth factor and platelet-rich plasma promoted angiogenesis, tendon maturing and fibrocartilage regeneration at the enthesis, which could enhance the mechanical strength. It was suggested that combined basic fibroblast growth factor and platelet-rich plasma might enhance both tendon and bone-tendon junction healing, and basic fibroblast growth factor and platelet-rich plasma might be synergistic.

Keywords

References

  1. J Bone Joint Surg Am. 2008 Nov;90(11):2423-31 [PMID: 18978411]
  2. J Orthop Surg Res. 2018 Aug 13;13(1):200 [PMID: 30103783]
  3. Regen Ther. 2019 May 10;11:41-46 [PMID: 31193122]
  4. Am J Sports Med. 2016 Jul;44(7):1735-43 [PMID: 27159292]
  5. J Bone Joint Surg Am. 2006 Sep;88(9):2027-34 [PMID: 16951120]
  6. Acta Biomater. 2012 May;8(5):1792-801 [PMID: 22293581]
  7. Am J Sports Med. 2015 Oct;43(10):2411-22 [PMID: 26311443]
  8. Am J Sports Med. 2008 Jul;36(7):1298-309 [PMID: 18354143]
  9. Tissue Eng. 2007 May;13(5):1103-12 [PMID: 17348798]
  10. Biomaterials. 2014 Dec;35(37):9904-9911 [PMID: 25236536]
  11. Thromb Haemost. 2004 Jan;91(1):4-15 [PMID: 14691563]
  12. Arthroscopy. 2005 Nov;21(11):1307-16 [PMID: 16325080]
  13. Tissue Eng Part A. 2015 Jul;21(13-14):2025-33 [PMID: 25819324]
  14. J Bone Joint Surg Am. 2009 May;91(5):1172-80 [PMID: 19411466]
  15. Am J Sports Med. 2011 Jun;39(6):1217-25 [PMID: 21427446]
  16. Am J Sports Med. 2008 Sep;36(9):1824-8 [PMID: 18753683]
  17. J Knee Surg. 2015 Feb;28(1):3-10 [PMID: 25068847]
  18. Curr Med Res Opin. 2018 Jul;34(7):1217-1229 [PMID: 28952378]
  19. J Shoulder Elbow Surg. 2009 May-Jun;18(3):391-8 [PMID: 19393930]
  20. Am J Vet Res. 1985 Oct;46(10):2091-6 [PMID: 4062012]
  21. Arthrosc Tech. 2016 Oct 31;5(6):e1235-e1238 [PMID: 28149719]
  22. Arch Orthop Trauma Surg. 2014 Mar;134(3):405-11 [PMID: 24379006]
  23. J Tissue Eng Regen Med. 2019 Mar;13(3):423-432 [PMID: 30644168]
  24. Am J Sports Med. 2012 Apr;40(4):786-93 [PMID: 22307079]
  25. Am J Sports Med. 2011 Feb;39(2):258-65 [PMID: 21160018]
  26. J Shoulder Elbow Surg. 2007 Sep-Oct;16(5 Suppl):S198-203 [PMID: 17903711]
  27. J Orthop Res. 2017 Feb;35(2):289-296 [PMID: 27171575]
  28. Am J Sports Med. 2010 Dec;38(12):2435-42 [PMID: 21030564]
  29. J R Soc Interface. 2009 Jun 6;6 Suppl 3:S311-24 [PMID: 19324684]
  30. Arthroscopy. 2011 Apr;27(4):453-62 [PMID: 21444007]
  31. Sports Med Arthrosc Rehabil Ther Technol. 2011 Dec 02;3:29 [PMID: 22136125]
  32. J Biomed Mater Res B Appl Biomater. 2004 Nov 15;71(2):252-9 [PMID: 15455368]
  33. Am J Sports Med. 2011 Oct;39(10):2108-16 [PMID: 21350064]
  34. J Tissue Eng Regen Med. 2012 Apr;6(4):291-8 [PMID: 21706776]
  35. J Bone Joint Surg Br. 2003 Mar;85(2):282-7 [PMID: 12678370]
  36. J Bone Miner Res. 2012 May;27(5):1118-31 [PMID: 22275312]
  37. Tissue Eng Part A. 2013 May;19(9-10):1233-43 [PMID: 23198912]

MeSH Term

Animals
Collagen Type II
Eosine Yellowish-(YS)
Fibroblast Growth Factor 2
Gelatin
Hematoxylin
Hydrogels
Lectins
Platelet-Rich Plasma
Rats
Rats, Sprague-Dawley
Rotator Cuff
Rotator Cuff Injuries
Wound Healing

Chemicals

Collagen Type II
Hydrogels
Lectins
Fibroblast Growth Factor 2
Gelatin
Eosine Yellowish-(YS)
Hematoxylin

Word Cloud

Created with Highcharts 10.0.0groupcufffibroblastgrowthfactorplasmabasicplatelet-richcombinedrotatortendonstainingrepairhealingtherapycontrolhigherpostoperativeenhanceratgelatin-hydrogelsheet2 weeksgroupssignificantlytearsreportedtearmodelinfraspinatusbFGFPRPusinghematoxylineosinsafraninOB4IIcollagenpostoperativelymechanicalultimatefailureloadmaturingCombinedmightRotatorINTRODUCTION:ExcellentoutcomesarthroscopicsmallmediumrecentlyHoweverre-tearssurgerycommoncomplicationsurgicallargemassiveoftenoccurearlyphasepreviouslyenhancedhypothesizedstudyaimedevaluateefficacyMETHODS:createdefectSpragueDawleyresectedgreatertuberositytendonsrepairedcoveredimpregnatedPBSHistologicalexaminationsconductedimmunofluorescenceIsolectintypeanalysistendon-humeralheadcomplexevaluated6 weeksRESULTS:scorestrongerproteoglycanobservedcomparedVascularisolectin3treatmentTypeexpressionCONCLUSION:promotedangiogenesisfibrocartilageregenerationenthesisstrengthsuggestedbone-tendonjunctionsynergisticmodelsBasicInfraspinatusPlatelet-richRat

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