Original Article| Volume 28, ISSUE 9, P1297-1305, September 2012

Download started.


Inhibitory Effect of Synovial Fluid on Tendon-to-Bone Healing: An Experimental Study in Rabbits


      The purpose of this study was to explore the effects of joint synovial fluid on tendon-to-bone healing in intra-articular ligament reconstruction of the knee.


      We divided 40 female New Zealand white rabbits into 4 groups randomly, with 10 animals in each group. Transfer of the semitendinosus tendon to the tibial bone tunnel was performed to create tendon-to-bone healing models. An intra-articular bone tunnel (IBT) was used on the left side and an extra-articular bone tunnel (EBT) on the right. Histologic evaluation was performed at 2, 4, and 8 weeks after the operation and biomechanical testing at 8 weeks.


      On the basis of fibroblast proliferation, collagen fiber density, collagen fiber orientation, and tendon-to-bone connection, histologic scores were significantly lower in the IBT group than in the EBT group at 2, 4, and 8 weeks. Cell counts per high-power field at the tendon-bone interface were significantly lower in the IBT group than in the EBT group at 2 and 4 weeks. In addition, biomechanical testing showed that the IBT group was significantly inferior to the EBT group in terms of ultimate failure load, yield load, and stiffness. There was also a significant difference between the 2 groups in failure mode.


      Joint synovial fluid appeared to have an inhibitory effect on tendon-to-bone healing in rabbits at an early stage.

      Clinical Relevance

      Our findings imply that prevention of infiltration of joint synovial fluid into the bone tunnel might be beneficial in improving the clinical outcome of cruciate ligament reconstruction of the knee.
      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 to Arthroscopy
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Petersen W.
        • Laprell H.
        Insertion of autologous tendon grafts to the bone: A histological and immunohistochemical study of hamstring and patellar tendon grafts.
        Knee Surg Sports Traumatol Arthrosc. 2000; 8: 26-31
        • Robert H.
        • Es-Sayeh J.
        • Heymann D.
        • Passuti N.
        • Eloit S.
        • Vaneenoge E.
        Hamstring insertion site healing after anterior cruciate ligament reconstruction in patients with symptomatic hardware or repeat rupture: A histologic study in 12 patients.
        Arthroscopy. 2003; 19: 948-954
        • Mutsuzaki H.
        • Sakane M.
        Calcium phosphate-hybridized tendon graft to enhance tendon-bone healing two years after ACL reconstruction in goats.
        Sports Med Arthrosc Rehabil Ther Technol. 2011; 3: 31
        • Vavken P.
        • Sadoghi P.
        • Murray M.M.
        The effect of platelet concentrates on graft maturation and graft-bone interface healing in anterior cruciate ligament reconstruction in human patients: A systematic review of controlled trials.
        Arthroscopy. 2011; 27: 1573-1583
        • Kondo E.
        • Yasuda K.
        • Katsura T.
        • Hayashi R.
        • Kotani Y.
        • Tohyama H.
        Biomechanical and histological evaluations of the doubled semitendinosus tendon autograft after anterior cruciate ligament reconstruction in sheep.
        Am J Sports Med. 2012; 40: 315-324
        • Scheffler S.U.
        • Unterhauser F.N.
        • Weiler A.
        Graft remodeling and ligamentization after cruciate ligament reconstruction.
        Knee Surg Sports Traumatol Arthrosc. 2008; 16: 834-842
        • Ekdahl M.
        • Wang J.H.
        • Ronga M.
        • Fu F.H.
        Graft healing in anterior cruciate ligament reconstruction.
        Knee Surg Sports Traumatol Arthrosc. 2008; 16: 935-947
        • Ekdahl M.
        • Nozaki M.
        • Ferretti M.
        • Tsai A.
        • Smolinski P.
        • Fu F.H.
        The effect of tunnel placement on bone-tendon healing in anterior cruciate ligament reconstruction in a goat model.
        Am J Sports Med. 2009; 37: 1522-1530
        • Zantop T.
        • Weimann A.
        • Wolle K.
        • Musahl V.
        • Langer M.
        • Petersen W.
        Initial and 6 weeks postoperative structural properties of soft tissue anterior cruciate ligament reconstructions with cross-pin or interference screw fixation: An in vivo study in sheep.
        Arthroscopy. 2007; 23: 14-20
        • Yamakado K.
        • Kitaoka K.
        • Yamada H.
        • Hashiba K.
        • Nakamura R.
        • Tomita K.
        The influence of mechanical stress on graft healing in a bone tunnel.
        Arthroscopy. 2002; 18: 82-90
        • Ikeda K.
        • Yamauchi D.
        • Osamura N.
        • Hagiwara N.
        • Tomita K.
        Hyaluronic acid prevents peripheral nerve adhesion.
        Br J Plast Surg. 2003; 56: 342-347
        • Tüzüner A.
        • Kuzu M.A.
        • Akin B.
        • Karaca S.
        • Hazinedaroglu S.
        The effect of hyaluronan-based agents on adhesion formation in an intraabdominal sepsis model.
        Dig Dis Sci. 2004; 49: 1054-1061
        • Akeson W.H.
        • Massie J.B.
        • Huang B.
        • et al.
        Topical high-molecular-weight hyaluronan and a roofing barrier sheet equally inhibit postlaminectomy fibrosis.
        Spine J. 2005; 5: 180-190
        • Higuchi H.
        • Shirakura K.
        • Kimura M.
        • et al.
        Changes in biochemical parameters after anterior cruciate ligament injury.
        Int Orthop. 2006; 30: 43-47
        • Demirag B.
        • Sarisozen B.
        • Ozer O.
        • Kaplan T.
        • Ozturk C.
        Enhancement of tendon-bone healing of anterior cruciate ligament grafts by blockage of matrix metalloproteinases.
        J Bone Joint Surg Am. 2005; 87: 2401-2410
        • Bedi A.
        • Kovacevic D.
        • Hettrich C.
        • et al.
        The effect of matrix metalloproteinase inhibition on tendon-to-bone healing in a rotator cuff repair model.
        J Shoulder Elbow Surg. 2010; 19: 384-391
        • Bedi A.
        • Fox A.J.
        • Kovacevic D.
        • Deng X.H.
        • Warren R.F.
        • Rodeo S.A.
        Doxycycline-mediated inhibition of matrix metalloproteinases improves healing after rotator cuff repair.
        Am J Sports Med. 2010; 38: 308-317
        • Berg E.E.
        • Pollard M.E.
        • Kang Q.
        Interarticular bone tunnel healing.
        Arthroscopy. 2001; 17: 189-195
        • Fuchs T.F.
        • Petersen W.
        • Vordemvenne T.
        • Stange R.
        • Raschke M.
        • Paletta J.R.
        Influence of synovial fluid on human osteoblasts: An in vitro study.
        Sci World J. 2007; 18: 2012-2020
        • Bedi A.
        • Kawamura S.
        • Ying L.
        • Rodeo S.A.
        Differences in tendon graft healing between the intra-articular and extra-articular ends of a bone tunnel.
        HSS J. 2009; 5: 51-57
        • Wen C.Y.
        • Qin L.
        • Lee K.M.
        • Wong M.W.
        • Chan K.M.
        Grafted tendon healing in tibial tunnel is inferior to healing in femoral tunnel after anterior cruciate ligament reconstruction: A histomorphometric study in rabbits.
        Arthroscopy. 2010; 26: 58-66
        • Nebelung W.
        • Becker R.
        • Urbach D.
        • Röpke M.
        • Roessner A.
        Histological findings of tendon-bone healing following anterior cruciate ligament reconstruction with hamstring grafts.
        Arch Orthop Trauma Surg. 2003; 123: 158-163
        • Tsuda E.
        • Fukuda Y.
        • Loh J.C.
        • Debski R.E.
        • Fu F.H.
        • Woo S.L.
        The effect of soft-tissue graft fixation in anterior cruciate ligament reconstruction on graft-tunnel motion under anterior tibial loading.
        Arthroscopy. 2002; 18: 960-967
        • Weiler A.
        • Hoffmann R.F.
        • Bail H.J.
        • Rehm O.
        • Südkamp N.P.
        Tendon healing in a bone tunnel.
        Arthroscopy. 2002; 18: 124-135
        • Hunt P.
        • Rehm O.
        • Weiler A.
        Soft tissue graft interference fit fixation: Observations on graft insertion site healing and tunnel remodeling 2 years after ACL reconstruction in sheep.
        Knee Surg Sports Traumatol Arthrosc. 2006; 14: 1245-1251
        • Karaoglu S.
        • Celik C.
        • Korkusuz P.
        The effects of bone marrow or periosteum on tendon-to-bone tunnel healing in a rabbit model.
        Knee Surg Sports Traumatol Arthrosc. 2009; 17: 170-178
        • Kyung H.S.
        • Kim S.Y.
        • Oh C.W.
        • Kim S.J.
        Tendon-to-bone tunnel healing in a rabbit model: The effect of periosteum augmentation at the tendon-to-bone interface.
        Knee Surg Sports Traumatol Arthrosc. 2003; 11: 9-15
        • Harvey A.
        • Thomas N.P.
        • Amis A.A.
        Fixation of the graft in reconstruction of the anterior cruciate ligament.
        J Bone Joint Surg Br. 2005; 87: 593-603
        • Tsukada H.
        • Ishibashi Y.
        • Tsuda E.
        • Kusumi T.
        • Kohno T.
        • Toh S.
        The actual tendon-bone interface strength in a rabbit model.
        Arthroscopy. 2010; 26: 366-374
        • Sun L.
        • Ning Z.J.
        • Zhang H.
        • Tian M.
        • Ning T.M.
        Arthroscopic single-bundle reconstruction of posterior cruciate ligament with quadrupled hamstring tendon.
        Chin J Traumatol. 2007; 10: 23-28
        • Jung Y.B.
        • Jung H.J.
        • Song K.S.
        • Kim J.Y.
        • Lee H.J.
        • Lee J.S.
        Remnant posterior cruciate ligament-augmenting stent procedure for injuries in the acute or subacute stage.
        Arthroscopy. 2010; 26: 223-229
        • Lee B.I.
        • Kwon S.W.
        • Kim J.B.
        • Choi H.S.
        • Min K.D.
        Comparison of clinical results according to amount of preserved remnant in arthroscopic anterior cruciate ligament reconstruction using quadrupled hamstring graft.
        Arthroscopy. 2008; 24: 560-568
        • Lee B.I.
        • Min K.D.
        • Choi H.S.
        • Kim J.B.
        • Kim S.T.
        Arthroscopic anterior cruciate ligament reconstruction with the tibial-remnant preserving technique using a hamstring graft.
        Arthroscopy. 2006; 22: e1-e7
        • Gulotta L.V.
        • Kovacevic D.
        • Ying L.
        • Ehteshami J.R.
        • Montgomery S.
        • Rodeo S.A.
        Augmentation of tendon-to-bone healing with a magnesium-based bone adhesive.
        Am J Sports Med. 2008; 36: 1290-1297
        • Wen C.Y.
        • Qin L.
        • Lee K.M.
        • Chan K.M.
        The use of brushite calcium phosphate cement for enhancement of bone-tendon integration in an anterior cruciate ligament reconstruction rabbit model.
        J Biomed Mater Res B Appl Biomater. 2009; 89: 466-474