Advertisement

The Effect of Intra-Articular Autogenous Bone Marrow Injection on Healing of an Acute Posterior Cruciate Ligament Injury in Rabbits

      Purpose

      The purpose was to identify the effect of intra-articular autogenous bone marrow injection on the healing of an acute posterior cruciate ligament (PCL) rupture in a rabbit model. The effect of autogenous bone marrow on the healing process was assessed serially by gross inspection, histologic examination, and immunohistochemical study of growth factors.

      Methods

      In both knee joints, the PCL was completely transected surgically near the femoral attachment site in 24 rabbits. Autogenous bone marrow was obtained from both tibias and delivered only to the right knee joint by direct intra-articular injection. Gross inspection, histologic examination, and immunohistochemical study of growth factors were performed at 8, 12, and 16 weeks after severing of the posterior cruciate ligament (PCL) among 8 randomly chosen specimens. The degree of healing in both marrow-stimulated and untreated control ligaments was evaluated by gross inspection using an ordinal scale consisting of 5 grades. The degree of fibroblast and vessel proliferation and alignment of collagen fibers were evaluated by histologic examination. The degree of expression of transforming growth factor β1, epidermal growth factor receptor, and vascular endothelial growth factor was evaluated by immunohistochemical study. Statistical analysis was performed with the Mann-Whitney U test.

      Results

      In the group with marrow-stimulated ligaments, the degree of healing was higher at 8 and 12 weeks by gross examination, whereas there was no significant difference at 16 weeks between the 2 groups. According to histologic examination, the healing process was faster in the bone marrow injection group than in the control group at 8 and 12 weeks because the degree of fibroblast and vessel proliferation significantly declined and collagen fibers were arranged more regularly compared with the control group. Similar to the results of histologic examination, the results of immunohistochemical studies showed that the healing process was faster in the bone marrow injection group. However, the recovery of the PCL was completed at 16 weeks after PCL resection in both the bone marrow injection group and the control group.

      Conclusions

      Intra-articular autogenous bone marrow injection appeared to promote the initiation of healing response in acutely injured PCLs in rabbits.

      Clinical Relevance

      Intra-articular autogenous bone marrow injection can be a viable option for treating acutely injured PCLs.
      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

        • Murphy J.M.
        • Fink D.J.
        • Hunziker E.B.
        • Barry F.P.
        Stem cell therapy in a caprine model of osteoarthritis.
        Arthritis Rheum. 2003; 48: 3464-3474
        • Grigolo B.
        • Lisignoli G.
        • Desando G.
        • Barry F.P.
        Osteoarthritis treated with mesenchymal stem cells on hyaluronan-based scaffold in rabbit.
        Tissue Eng Part C Methods. 2009; 15: 647-658
        • Hildebrand K.A.
        • Woo S.L.
        • Smith D.W.
        • Barry F.P.
        The effects of platelet-derived growth factor-BB on healing of the rabbit medial collateral ligament.
        Am J Sports Med. 1998; 26: 549-554
        • Kondo E.
        • Yasuda K.
        • Yamanaka M.
        • Minami A.
        • Tohyama H.
        Effects of administration of exogenous growth factors on biomechanical properties of the elongation-type anterior cruciate ligament injury with partial laceration.
        Am J Sports Med. 2005; 33: 188-196
        • Alm A.
        • Stromberg B.
        Vascular anatomy of the patellar and cruciate ligaments.
        Acta Chir Scand Suppl. 1974; 445: 25-35
        • Shelbourne K.D.
        • Davis T.J.
        • Patel D.V.
        The natural history of acute, isolated, nonoperatively treated posterior cruciate ligament injuries.
        Am J Sports Med. 1999; 27: 276-283
        • Jung Y.B.
        • Tae S.K.
        • Lee Y.S.
        • Jung H.J.
        • Nam C.H.
        • Park S.J.
        Active non-operative treatment of acute isolated posterior cruciate ligament injury with cylinder cast immobilization.
        Knee Surg Sports Traumatol Arthrosc. 2008; 16: 729-733
        • Jung Y.B.
        • Jung H.J.
        • Yang J.J.
        • Barry F.P.
        Characterization of spontaneous healing of chronic posterior cruciate ligament injury: Analysis of instability and magnetic resonance imaging.
        J Magn Reson Imaging. 2008; 27: 1336-1340
        • Keller P.M.
        • Shelbourne K.D.
        • McCarroll J.R.
        • Rettig A.C.
        Nonoperatively treated isolated posterior cruciate ligament injuries.
        Am J Sports Med. 1993; 21: 132-136
        • Iwata S.
        • Suda Y.
        • Nagura T.
        • Barry F.P.
        Clinical disability in posterior cruciate ligament deficient patients does not relate to knee laxity, but relates to dynamic knee function during stair descending.
        Knee Surg Sports Traumatol Arthrosc. 2007; 15: 335-342
        • Iwata S.
        • Suda Y.
        • Nagura T.
        • Matsumoto H.
        • Otani T.
        • Toyama Y.
        Posterior instability near extension is related to clinical disability in isolated posterior cruciate ligament deficient patients.
        Knee Surg Sports Traumatol Arthrosc. 2007; 15: 343-349
        • Eriksson E.
        Why are some PCL-ruptures almost symptom free and others have “giving-way” problems?.
        Knee Surg Sports Traumatol Arthrosc. 2007; 15: 319
        • Torg J.S.
        • Barton T.M.
        • Pavlov H.
        • Stine R.
        Natural history of the posterior cruciate ligament-deficient knee.
        Clin Orthop Relat Res. 1989; : 208-216
        • Bosch U.
        • Kasperczyk W.J.
        • Oestern H.J.
        • Tscherne H.
        Healing phases in autogenous posterior cruciate ligament replacement. A decision aid for after-care. A biomechanical and histologic study.
        Unfallchirurg. 1990; 93 (in German): 187-196
        • Frank C.
        • Amiel D.
        • Akeson W.H.
        Healing of the medial collateral ligament of the knee.
        Acta Orthop Scand. 1983; 54: 917-923
        • Frank C.
        • McDonald D.
        • Wilson J.
        • Eyre D.
        • Shrive N.
        Rabbit medial collateral ligament scar weakness is associated with decreased collagen pyridinoline crosslink density.
        J Orthop Res. 1995; 13: 157-165
        • Amiel D.
        • Nagineni C.N.
        • Choi S.H.
        • Lee J.
        Intrinsic properties of ACL and MCL cells and their responses to growth factors.
        Med Sci Sports Exerc. 1995; 27: 844-851
        • Murray M.M.
        • Martin S.D.
        • Martin T.L.
        • Spector M.
        Histological changes in the human anterior cruciate ligament after rupture.
        J Bone Joint Surg Am. 2000; 82: 1387-1397
        • Burwell R.G.
        The function of bone marrow in the incorporation of a bone graft.
        Clin Orthop Relat Res. 1985; : 125-141
        • Connolly J.
        • Guse R.
        • Lippiello L.
        • Dehne R.
        Development of an osteogenic bone-marrow preparation.
        J Bone Joint Surg Am. 1989; 71: 684-691
        • Laws G.
        • Walton M.
        Fibroblastic healing of grade II ligament injuries.
        J Bone Joint Surg Br. 1988; 70: 390-396
        • Lee J.
        • Harwood F.L.
        • Akeson W.H.
        • Amiel D.
        Growth factor expression in healing rabbit medial collateral and anterior cruciate ligaments.
        Iowa Orthop J. 1998; 18: 19-25
        • Kuroda R.
        • Kurosaka M.
        • Yoshiya S.
        • Mizuno K.
        Localization of growth factors in the reconstructed anterior cruciate ligament: Immunohistological study in dogs.
        Knee Surg Sports Traumatol Arthrosc. 2000; 8: 120-126
        • Gerber H.P.
        • Vu T.H.
        • Ryan A.M.
        • Kowalski J.
        • Werb Z.
        • Ferrara N.
        VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation.
        Nat Med. 1999; 5: 623-628
        • Lu H.
        • Qin L.
        • Cheung W.
        • Lee K.
        • Wong W.
        • Leung K.
        Low-intensity pulsed ultrasound accelerated bone-tendon junction healing through regulation of vascular endothelial growth factor expression and cartilage formation.
        Ultrasound Med Biol. 2008; 34: 1248-1260
        • Shelbourne K.D.
        • Jennings R.W.
        • Vahey T.N.
        Magnetic resonance imaging of posterior cruciate ligament injuries: Assessment of healing.
        Am J Knee Surg. 1999; 12: 209-213
        • Dejour H.
        • Walch G.
        Chronic posterior instabilities.
        Orthopade. 1987; 16 (in German): 149-156
        • Lee B.K.
        • Eom G.S.
        • Kee Y.C.
        Posterior laxity after conservative treatment of the acute injured posterior cruciate ligament.
        J Korean Knee Soc. 2003; 15: 97-101
        • Agung M.
        • Ochi M.
        • Yanada S.
        • Barry F.P.
        Mobilization of bone marrow-derived mesenchymal stem cells into the injured tissues after intraarticular injection and their contribution to tissue regeneration.
        Knee Surg Sports Traumatol Arthrosc. 2006; 14: 1307-1314
        • Cheng M.T.
        • Yang H.W.
        • Chen T.H.
        • Lee O.K.
        Isolation and characterization of multipotent stem cells from human cruciate ligaments.
        Cell Prolif. 2009; 42: 448-460
        • Kanaya A.
        • Deie M.
        • Adachi N.
        • Nishimori M.
        • Yanada S.
        • Ochi M.
        Intra-articular injection of mesenchymal stromal cells in partially torn anterior cruciate ligaments in a rat model.
        Arthroscopy. 2007; 23: 610-617
        • Rodkey W.G.
        • Arnoczky S.P.
        • Steadman J.R.
        Healing of a surgically created partial detachment of the posterior cruciate ligament using marrow stimulation: An experimental study in dogs.
        J Knee Surg. 2006; 19: 14-18
        • Ma Y.
        • Zhang X.
        • Wang J.
        • Barry F.P.
        Effect of bone morphogenetic protein-12 gene transfer on posterior cruciate ligament healing in a rabbit model.
        Am J Sports Med. 2009; 37: 599-609