Advertisement

Bone marrow-derived fibrin clots stimulate healing of a meniscal defect in a rabbit model

Published:December 24, 2022DOI:https://doi.org/10.1016/j.arthro.2022.12.013

      Abstract

      Purpose

      To determine the in vivo effectiveness of bone marrow aspirate-derived (BMA) fibrin clots for avascular meniscal defect healing in a rabbit model.

      Methods

      In 42 Japanese white rabbits, a 2.0-mm cylindrical defect was introduced into the avascular zone of the anterior part of the medial meniscus in the bilateral knees. The rabbits were grouped according to implantation of a BMA fibrin clot (BMA group) or a peripheral blood (PB)-derived clot (PB group) into the defect and non-implantation (control group). Macroscopic and histological assessments were performed using a scoring system at 4 and 12 weeks postoperatively. At 12 weeks postoperatively, compressive stress was analyzed biomechanically.

      Results

      The meniscal score in the BMA group (12.1) was greater than that in the PB group (5.5) (P = .031) and control group (4.4) (P = .013) at 4 weeks. The meniscal score in the BMA group (13.1) was greater than that in the control group (6.4) (BMA = 13.1, P = .0046) at 12 weeks. In the biomechanical analysis, the BMA group demonstrated significantly higher compressive strength than the PB group (6.6 MPa) (BMA = 15.4 MPa, P = .0201) and control group (3.6 MPa) (BMA = 15.4 MPa, P = .007)

      Conclusions

      Implantation of BMA fibrin clots into the meniscal defect of the avascular zone in a rabbit model improved the meniscal score at 4 weeks and strengthened the reparative meniscal tissue at 12 weeks compared with the implantation of PB fibrin clots.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Arthroscopy
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

      1. Asai K, Nakase J, Yoshioka K, Yoshimizu R, Kimura M, Tsuchiya H. Adipose-Derived Stem Cell Sheets Promote Meniscus Regeneration Regardless of Whether the Defect Involves the Inner Half or the Whole Width of the Anterior Half of the Medial Meniscus in a Rabbit Model. Arthroscopy. 2022 Mar 4;S0749-8063(22)00141-4.

        • Takata Y.
        • Nakase J.
        • Shimozaki K.
        • Asai K.
        • Tsuchiya H.
        Autologous Adipose-Derived Stem Cell Sheet Has Meniscus Regeneration-Promoting Effects in a Rabbit Model.
        Arthroscopy. 2020; 36: 2698-2707
        • Toratani T.
        • Nakase J.
        • Numata H.
        • Oshima T.
        • Takata Y.
        • Nakayama K.
        • Tsuchiya H.
        Scaffold-Free Tissue-Engineered Allogenic Adipose-Derived Stem Cells Promote Meniscus Healing.
        Arthroscopy. 2017 Feb; 33: 346-354
        • Ozeki N.
        • Kohno Y.
        • Kushida Y.
        • Watanabe N.
        • Mizuno M.
        • Katano H.
        • Masumoto J.
        • Koga H.
        • Sekiya I.
        Synovial mesenchymal stem cells promote the meniscus repair in a novel pig meniscus injury model.
        J Orthop Res. 2021; 39: 177-183
        • Kondo S.
        • Muneta T.
        • Nakagawa Y.
        • Koga H.
        • Watanabe T.
        • Tsuji K.
        • Sotome S.
        • Okawa A.
        • Kiuchi S.
        • Ono H.
        • Mizuno M.
        • Sekiya I.
        Transplantation of Autologous Synovial Mesenchymal Stem Cells Promotes Meniscus Regeneration in Aged Primates.
        J Orthop Res. 2017; 35: 1274-1282
      2. Guo W, Xu W, Wang Z, Chen M, Hao C, Zheng X, Huang J, Sui X, Yuan Z, Zhang Y, Wang M, Li X, Wang Z, Peng J, Wang A, Wang Y, Liu S, Lu S, Guo Q. Cell-Free Strategies for Repair and Regeneration of Meniscus Injuries through the Recruitment of Endogenous Stem/Progenitor Cells. Stem Cells Int. 2018 Jul 12;2018:5310471.

        • Arnoczky S.P.
        • Warren R.F.
        Microvasculature of the human meniscus.
        Am J Sports Med. 1982; 10: 90-95
        • Mcdermott I.D.
        • Amis A.A.
        The consequences of meniscectomy.
        J Bone Joint Surg Br. 2006; 88: 1549-1556
        • McDermott I.D.
        • Lie D.T.T.
        • Edwards A.
        • Bull A.M.J.
        • Amis A.A.
        The effects of lateral meniscal allograft transplantation techniques on tibio-femoral contact pressures.
        Knee Surg Sports Traumatol Arthrosc. 2008; 16: 553-560
        • Fischenich K.M.
        • Lewis J.
        • Kindsfater K.A.
        • Bailey T.S.
        • Haut Donahue T.L.
        Effects of degeneration on the compressive and tensile properties of human meniscus.
        J Biomech. 2015; 48: 1407-1411
        • Otani S.
        • Kanamoto T.
        • Oyama S.
        • Yamakawa S.
        • Shi W.
        • Miyazaki R.
        • Aihara M.
        • Oka S.
        • Kuroda S.
        • Nakai T.
        • Takenaka K.
        • Sato Y.
        • Tsukamoto M.
        • Tsujii A.
        • Ebina K.
        • Okada S.
        • Nakata K.
        Meniscus surface texture is associated with degenerative changes in biological and biomechanical properties.
        Sci Rep. 2022; 1211977
        • Tachibana Y.
        • Mae T.
        • Fujie H.
        • Shino K.
        • Ohori T.
        • Yoshikawa H.
        • Nakata K.
        Effect of radial meniscal tear on in situ forces of meniscus and tibiofemoral relationship.
        Knee Surg Sports Traumatol Arthrosc. 2017; 25: 355-361
        • Muriuki M.G.
        • Tuason D.A.
        • Tucker B.G.
        • Harner C.D.
        Changes in tibiofemoral contact mechanics following radial split and vertical tears of the medial meniscus an in vitro investigation of the efficacy of arthroscopic repair.
        J Bone Joint Surg Am. 2011; 93: 1089-1095
        • Warnecke D.
        • Balko J.
        • Haas J.
        • Bieger R.
        • Leucht F.
        • Wolf N.
        • Schild N.B.
        • Stein S.E.C.
        • Seitz A.M.
        • Ignatius A.
        • Reichel H.
        • Mizaikoff B.
        • Dürselen L.
        Degeneration alters the biomechanical properties and structural composition of lateral human menisci.
        Osteoarthritis Cartilage. 2020; 28: 1482-1491
        • Moran C.J.
        • Busilacchi A.
        • Lee C.A.
        • Athanasiou K.A.
        • Verdonk P.C.
        Biological augmentation and tissue engineering approaches in meniscus surgery.
        Arthroscopy. 2015; 31: 944-955
        • Otsuki S.
        • Nakagawa K.
        • Murakami T.
        • Sezaki S.
        • Sato H.
        • Suzuki M.
        • Okuno N.
        • Wakama H.
        • Kaihatsu K.
        • Neo M.
        Evaluation of Meniscal Regeneration in a Mini Pig Model Treated With a Novel Polyglycolic Acid Meniscal Scaffold.
        Am J Sports Med. 2019; 47: 1804-1815
        • Chahla J.
        • Kennedy N.I.
        • Geeslin A.G.
        • Moatshe G.
        • Cinque M.E.
        • DePhillipo N.N.
        • LaPrade R.F.
        Meniscal Repair With Fibrin Clot Augmentation.
        Arthrosc Tech. 2017; 6: e2065-e2069
        • Bujoli B.
        • Scimeca J.C.
        • Verron E.
        Fibrin as a Multipurpose Physiological Platform for Bone Tissue Engineering and Targeted Delivery of Bioactive Compounds.
        Pharmaceutics. 2019; 11: 556
      3. Sekiya I, Koga H, Katano H, Mizuno M, Kohno Y, Otabe K, Ozeki N. Second-look arthroscopy after meniscus repair and synovial mesenchymal stem cell transplantation to treat degenerative flaps and radial tears of the medial meniscus: A case report. J Orthop Sci. 2021 Jun 10;S0949-2658(21)00152-00154.

        • Sekiya I.
        • Koga H.
        • Katano H.
        • Otabe K.
        • Nakagawa Y.
        • Katano H.
        • Ozeki N.
        • Mizuno M.
        • Horie M.
        • Kohno Y.
        • Katagiri K.
        • Watanabe N.
        • Muneta T.
        Additional Use of Synovial Mesenchymal Stem Cell Transplantation Following Surgical Repair of a Complex Degenerative Tear of the Medial Meniscus of the Knee: A Case Report.
        Cell Transplant. 2019; 28: 1445-1454
        • Olivos-Meza A.
        • Jiménez F.J.P.
        • Granados-Montiel J.
        • Landa-Solís C.
        • González S.C.
        • Aroche C.A.J.
        • Chávez M.V.
        • León S.R.
        • Gomez-Garcia R.
        • Martínez-López V.
        • Ortega-Sánchez C.
        • Parra-Cid C.
        • Martinez C.V.
        • Ibarra C.
        First Clinical Application of Polyurethane Meniscal Scaffolds with Mesenchymal Stem Cells and Assessment of Cartilage Quality with T2 Mapping at 12 Months.
        Cartilage. 2021; 13: 197S-207S
        • Whitehouse M.R.
        • Howells N.R.
        • Parry M.C.
        • Austin E.
        • Kafienah W.
        • Brady K.
        • Goodship A.E.
        • Eldridge J.D.
        • Blom A.W.
        • Hollander A.P.
        Repair of Torn Avascular Meniscal Cartilage Using Undifferentiated Autologous Mesenchymal Stem Cells: From In Vitro Optimization to a First-in-Human Study.
        Stem Cells Transl Med. 2017; 6: 1237-1248
        • Nakayama H.
        • Kanto R.
        • Kambara S.
        • Iseki T.
        • Onishi S.
        • Yoshiya S.
        Successful treatment of degenerative medial meniscal tears in well-aligned knees with fibrin clot implantation.
        Knee Surg Sports Traumatol Arthrosc. 2020; 28: 3466-3473
        • Hashimoto Y.
        • Nishino K.
        • Orita K.
        • Yamasaki S.
        • Nishida Y.
        • Kinoshita T.
        • Nakamura H.
        Biochemical Characteristics and Clinical Result of Bone MarroweDerived Fibrin Clot for Repair of Isolated Meniscal Injury in the Avascular Zone.
        Arthroscopy. 2022; 38: 441-449
        • Steadman J.R.
        • Briggs K.K.
        • Rodrigo J.J.
        • Kocher M.S.
        • Gill T.J.
        • Rodkey W.G.
        Outcomes of microfracture for traumatic chondral defects of the knee: Average 11-year follow-up.
        Arthroscopy. 2003; 19: 477-484
        • Frisbie D.D.
        • Trotter G.W.
        • Powers B.E.
        • Rodkey W.G.
        • Steadman J.R.
        • Howard R.D.
        • Park R.D.
        • McIlwraith C.W.
        Arthroscopic subchondral bone plate microfracture technique augments healing of large chondral defects in the radial carpal bone and medial femoral condyle of horses.
        Vet Surg. 1999; 28: 242-255
        • Kramer J.
        • Böhrnsen F.
        • Lindner U.
        • Behrens P.
        • Schlenke P.
        • Rohwedel J.
        In vivo matrix-guided human mesenchymal stem cells.
        Cell Mol Life Sci. 2006; 63: 616-626
        • Liu F.
        • Xu H.
        • Huang H.
        A novel kartogenin-platelet-rich plasma gel enhances chondrogenesis of bone marrow mesenchymal stem cells in vitro and promotes wounded meniscus healing in vivo.
        Stem Cell Res Ther. 2019; 10: 201
        • Brown C.
        • McKee C.
        • Bakshi S.
        • Walker K.
        • Hakman E.
        • Halassy S.
        • Svinarich D.
        • Dodds R.
        • Govind C.K.
        • Chaudhry G.R.
        Mesenchymal stem cells: Cell therapy and regeneration potential.
        J Tissue Eng Regen Med. 2019; 13: 1738-1755
        • Smiler D.
        • Soltan M.
        • Albitar M.
        Toward the identification of mesenchymal stem cells in bone marrow and peripheral blood for bone regeneration.
        Implant Dent. 2008; 17: 236-247
      4. Yao Q, Wei B, Liu N, Li C, Guo Y, Shamie AN, Chen J, Tang C, Jin C, Xu Y, Bian X, Zhang X, Wang L. Chondrogenic regeneration using bone marrow clots and a porous polycaprolactone-hydroxyapatite scaffold by three-dimensional printing. Tissue Eng Part A. 2015;21(7-8):1388-1397.

        • Salamanna F.
        • Contartese D.
        • Aldini N.N.
        • Brodano G.B.
        • Griffoni C.
        • Gasbarrini A.
        • Fini M.
        Bone marrow aspirate clot: A technical complication or a smart approach for musculoskeletal tissue regeneration?.
        J Cell Physiol. 2018; 233: 2723-2732
        • Shoji T.
        • Nakasa T.
        • Yoshizuka M.
        • Yamasaki T.
        • Yasunaga Y.
        • Adachi N.
        • Ochi M.
        Comparison of fibrin clots derived from peripheral blood and bone marrow.
        Connect Tissue Res. 2017; 58: 208-214
        • Henning C.E.
        • Yearout K.M.
        • Vequist S.W.
        • Stallbaumer R.J.
        • Decker K.A.
        Use of the fascia sheath coverage and exogenous fibrin clot in the treatment of complex meniscal tears.
        Am J Sports Med. 1991; 19: 626-631
        • Kamimura T.
        • Kimura M.
        Meniscal Repair of Degenerative Horizontal Cleavage Tears Using Fibrin Clots: Clinical and Arthroscopic Outcomes in 10 Cases.
        Orthop J Sports Med. 2014; 22325967114555678
      5. Arnoczky SP, Warren RF, Spivak JM. Meniscal repair using an exogenous fibrin clot. An experimental study in dogs. J Bone Joint Surg Am. 1988;70(8):1209-1217.

        • Zellner J.
        • Hierl K.
        • Mueller M.
        • Pfeifer C.
        • Berner A.
        • Dienstknecht T.
        • Krutsch W.
        • Geis S.
        • Gehmert S.
        • Kujat R.
        • Dendorfer S.
        • Prantl L.
        • Nerlich M.
        • Angele P.
        Stem cell-based tissue-engineering for treatment of meniscal tears in the avascular zone.
        J Biomed Mater Res B Appl Biomater. 2013; 101: 1133-1142
      6. Kim WY, Onodera T, Kondo E, Terkawi MA, Homan K, Hishimura R, Iwasaki N. Which Contributes to Meniscal Repair, the Synovium or the Meniscus? An In Vivo Rabbit Model Study With the Freeze-Thaw Method. Am J Sports Med. 2020;48(6):1406-1415.

        • Lamplot J.D.
        • Tompkins W.P.
        • Friedman M.V.
        • Nguyen J.T.
        • Rai M.F.
        • Brophy R.H.
        Radiographic and Clinical Evidence for Osteoarthritis at Medium-Term Follow-up after Arthroscopic Partial Medial Meniscectomy.
        Cartilage. 2021; 13: 588S-594S
        • Woodmass J.M.
        • LaPrade R.F.
        • Sgaglione N.A.
        • Nakamura N.
        • Krych A.J.
        Meniscal Repair: Reconsidering Indications, Techniques, and Biologic Augmentation.
        J Bone Joint Surg Am. 2017; 99: 1222-1231
        • Caplan A.E.
        • Dennis J.E.
        Mesenchymal stem cells as trophic mediators.
        J Cell Biochem. 2006; 98: 1076-1084
        • Zellner J.
        • Mueller M.
        • Berner A.
        • Dienstknecht T.
        • Kujat R.
        • Nerlich M.
        • Hennemann B.
        • Koller M.
        • Prantl L.
        • Angele M.
        • Angele P.
        Role of mesenchymal stem cells in tissue engineering of meniscus.
        J Biomed Mater Res A. 2010; 94: 1150-1161
        • Koch M.
        • Hammer S.
        • Fuellerer J.
        • Lang S.
        • Pfeifer C.G.
        • Pattappa G.
        • Weber J.
        • Loibl M.
        • Nerlich M.
        • Angele P.
        • Zellner J.
        Bone Marrow Aspirate Concentrate for the Treatment of Avascular Meniscus Tears in a One-Step Procedure-Evaluation of an In Vivo Model.
        Int J Mol Sci. 2019; 20: 1120
        • Voss A.
        • McCarthy M.B.
        • Allen D.
        • Cote M.P.
        • Beitzel K.
        • Imhoff A.B.
        • Mazzocca A.D.
        Fibrin Scaffold as a Carrier for Mesenchymal Stem Cells and Growth Factors in Shoulder Rotator Cuff Repair.
        Arthrosc Tech. 2016; 5: e447-e451
        • Fortier L.A.
        • Potter H.G.
        • Rickey E.J.
        • Schnabel L.V.
        • Foo L.F.
        • Chong L.R.
        • Stokol T.
        • Cheetham J.
        • Nixon A.J.
        Concentrated bone marrow aspirate improves full-thickness cartilage repair compared with microfracture in the equine model.
        J Bone Joint Surg Am. 2010; 92: 1927-1937
        • Kaminski R.
        • Kulinski K.
        • Kaminska K.K.
        • Wasko M.K.
        • Langner M.
        • Pomianowski S.
        Repair Augmentation of Unstable, Complete Vertical Meniscal Tears With Bone Marrow Venting Procedure: A Prospective, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study.
        Arthroscopy. 2019; 35: 1500-1508.e1
        • Zhang S.
        • Matsushita T.
        • Kuroda R.
        • Nishida K.
        • Matsuzaki T.
        • Matsumoto T.
        • Takayama K.
        • Nagai K.
        • Oka S.
        • Tabata Y.
        • Nagamune K.
        • Kurosaka M.
        Local Administration of Simvastatin Stimulates Healing of an Avascular Meniscus in a Rabbit Model of a Meniscal Defect.
        Am J Sports Med. 2016; 44: 1735-1743
        • Horie M.
        • Driscoll M.D.
        • Sampson H.W.
        • Sekiya I.
        • Caroom C.T.
        • Prockop D.J.
        • Thomas D.B.
        Implantation of allogenic synovial stem cells promotes meniscal regeneration in a rabbit meniscal defect model.
        J Bone Joint Surg Am. 2012; 94: 701-712
        • Welsing R.T.C.
        • Tienen T.G.V.
        • Ramrattan N.
        • Heijkants R.
        • Schouten A.J.
        • Veth R.P.H.
        • Buma P.
        Effect on tissue differentiation and articular cartilage degradation of a polymer meniscus implant: A 2-year follow-up study in dogs.
        Am J Sports Med. 2008; 36: 1978-1989