Structural and Functional Modulation of Early Healing of Full-thickness Superficial Digital Flexor Tendon Rupture in Rabbits by Repeated Subcutaneous Administration of Exogenous Human Recombinant Basic Fibroblast Growth Factor

  • Ali Moshiri
    Research Assistant, Veterinary Surgery and Radiology, Department of Surgery and Radiology, Shiraz University School of Veterinary Medicine, Shiraz, Iran
    Search for articles by this author
  • Ahmad Oryan
    Address correspondence to: Ahmad Oryan, DVM, PhD, Professor of Comparative Pathology, Department of Pathology, Shiraz University School of Veterinary Medicine, Shiraz, Fars 71345 Iran.
    Professor of Comparative Pathology, Department of Pathology, Shiraz University School of Veterinary Medicine, Shiraz, Iran
    Search for articles by this author


      The present study was designed to investigate the effects of basic fibroblast growth factor on the healing of the acute phase of complete superficial digital flexor tendon rupture in rabbits. A total of 40 skeletally mature female white New Zealand rabbits were randomly divided into 2 equal groups of injured treated and injured control. After tenotomy and surgical anastomosis, using a modified Kessler and running pattern, the injured legs were placed in casts for 14 days, and basic fibroblast growth factor was injected subcutaneously over the lesion on days 3, 7, and 10 after injury. The injured control rabbits received a normal saline injection in a similar protocol. The rabbits' weight, tendon diameter, clinical signs, radiographs, and ultrasound scans were evaluated weekly. The rabbits were killed 28 days after injury, and the tendons were evaluated at the macroscopic, histopathologic, and ultrastructural levels and for biomechanical and the percentage of dry weight analysis. Treatment significantly reduced the diameter and increased the echogenicity and dry weight content and enhanced the maturation rate of the tenoblasts, fibrillogenesis, collagen fibril diameter, fibrillar density, tensile strength, and stiffness and stress of the injured tendons. Treatment with basic fibroblast growth factor was effective in restoring the morphologic and biomechanical properties of the injured superficial digital flexor tendon and could be valuable in clinical trial studies.

      Level of Clinical Evidence


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic and Personal
      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 The Journal of Foot and Ankle Surgery
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Chan B.P.
        • Fu S.
        • Qin L.
        • Lee K.
        • Rolf C.G.
        • Chan K.
        Effects of basic fibroblast growth factor (bFGF) on early stages of tendon healing: a rat patellar tendon model.
        Acta Orthop Scand. 2000; 71: 513-518
        • Sharma P.
        • Maffulli N.
        Tendon injury and tendinopathy: healing and repair.
        J Bone Joint Surg [Am]. 2005; 87: 187-202
        • Gospodarowicz D.
        • Ferrara N.
        • Schweigerer L.
        • Neufeld G.
        Structural characterization and biological functions of fibroblast growth factor.
        Endocr Rev. 1987; 8: 95-114
        • McNeil P.L.
        • Muthukrishnan L.
        • Warder E.D.
        • D'Amore P.A.
        Growth factors are released by mechanically wounded endothelial cells.
        J Cell Biol. 1989; 109: 811-822
        • Post M.J.
        • Laham R.
        • Sellke F.W.
        • Simons M.
        Therapeutic angiogenesis in cardiology using protein formulations.
        Cardiovasc Res. 2001; 49: 522-531
        • Takeuchi R.
        The effect of basic fibroblast growth factor on cell cycle in human gingival fibroblasts from nifedipine responder and non-responder.
        J Oral Sci. 2004; 46: 37-44
        • Wronski T.J.
        Skeletal effects of systemic treatment with basic fibroblast growth factor.
        J Musculoskel Neuron Interact. 2001; 2: 9-14
        • Zakine G.
        • Ermisch C.
        • Loaille B.
        • Fornes P.
        • Sapoval M.
        • Courty J.
        • Caruelle J.P.
        • Barritault D.
        • Carpentier A.
        • Chachques J.C.
        Comparison of two ways of administration of growth factors (bFGF and RGTA) to improve latissimus dorsi muscle flap vascularization and trophicity.
        Basic Appl Myol. 2006; 16: 9-15
        • Oi Y.
        • Ota M.
        • Yamamoto S.
        • Shibukava Y.
        • Yamada S.
        β-Tricalcium phosphate and basic fibroblast growth factor combination enhances periodontal regeneration in intrabony defects in dogs.
        Dent Mater J. 2009; 28: 162-169
        • Fisher M.
        • Meadows M.E.
        • Do T.
        • Weise J.
        • Trubetskoy V.
        • Charette M.
        • Finklestein S.P.
        Delayed treatment with intravenous basic fibroblast growth factor reduces infarct size following permanent focal cerebral ischemia in rats.
        J Cereb Blood Flow Metab. 1995; 15: 953-959
        • Koketsu N.
        • Berlove D.J.
        • Moskowitz M.A.
        • Kowall N.W.
        • Caday C.G.
        • Finklestein S.P.
        Pretreatment with intraventricular basic fibroblast growth factor (bFGF) decreases infarct size following focal cerebral ischemia in rats.
        Ann Neurol. 1994; 35: 451-457
        • Mattson M.P.
        • Scheff S.W.
        Endogenous neuroprotection factors and traumatic brain injury: mechanisms of action and implications for therapy.
        J Neurotrauma. 1994; 11: 3-33
        • Oryan A.
        • Shoushtari A.H.
        Histology and ultrastructure of the developing superficial digital flexor tendon in rabbits.
        Anat Histol Embryol. 2008; 37: 134-140
        • Oryan A.
        • Shoushtari A.H.
        Biomechanical properties and dry weight content of the developing superficial digital flexor tendon in rabbit.
        Comp Clin Pathol. 2009; 18: 131-137
        • Oryan A.
        • Silver I.A.
        • Goodship A.E.
        Metrenperone enhances collagen turnover and remodeling in the early stages of healing of tendon injury in rabbit.
        Arch Orthop Trauma Surg. 2010; 130: 1451-1457
        • Jain A.
        • Nanchahal J.
        • Troeberg L.
        • Green P.
        • Brennan F.
        Production of cytokines, vascular endothelial growth factors, matrix metalloproteinase, and tissue inhibitor of metalloproteinases 1 by tenosynovium demonstrates its potential for tendon destruction in rheumatoid arthritis.
        Arthritis Rheum. 2001; 44: 1754-1760
        • Hu Y.F.
        • Wu Y.J.
        Effect of recombinant human basic fibroblast growth factor on acute inflammation of mice and rats.
        Acta Pharmacol Sin. 2001; 22: 375-379
        • Tang J.B.
        • Cao Y.
        • Zhu B.
        • Xin K.-Q.
        • Wang X.T.
        • Liu P.Y.
        Adeno-associated virus-2-mediated bFGF gene transfer to digital flexor tendons significantly increases healing strength: an in vivo study.
        J Bone Joint Surg [Am]. 2008; 90: 1078-1089
        • Hamada Y.
        • Katoh S.
        • Hibino N.
        • Kosaka H.
        • Hamada D.
        • Yasui N.
        Effects of monofilament nylon coated with basic fibroblast growth factor on endogenous intrasynovial flexor tendon healing.
        J Hand Surg [Am]. 2006; 31: 530-540
        • Molloy T.
        • Wang Y.
        • Murrell G.A.C.
        The roles of growth factors in tendon and ligament healing.
        Sports Med. 2003; 33: 381-394
        • Takahashi S.
        • Nakajima M.
        • Kobayashi M.
        • Wakabayashi I.
        • Miyakoshi N.
        • Minagawa H.
        • Itoi E.
        Effect of recombinant basic fibroblast growth factor (bFGF) on fibroblast-like cells from human rotator cuff tendon.
        Tohoku J Exp Med. 2002; 198: 207-214
        • Thomopoulos S.
        • Harwood F.L.
        • Silva M.J.
        • Amiel D.
        • Gelberman R.H.
        Effect of several growth factors on canine flexor tendon fibroblast proliferation and collagen synthesis in vitro.
        J Hand Surg [Am]. 2005; 30: 441-447
        • Gulotta L.V.
        • Rodeo S.A.
        Growth factors for rotator cuff repair.
        Clin Sports Med. 2009; 28: 13-23
        • Oryan A.
        • Goodship A.E.
        • Silver I.A.
        Response of a collagenase-induced tendon injury to treatment with a polysulphated glycosaminoglycan (Adequan).
        Connect Tissue Res. 2008; 49: 351-360
        • MacKay D.
        • Miller A.L.
        Nutritional support for wound healing.
        Altern Med Rev. 2003; 8: 359-377
        • Heldin P.
        • Laurent T.C.
        • Heldin C.H.
        Effect of growth factors on hyaluronan synthesis in cultured human fibroblasts.
        Biochem J. 1989; 258: 919-922
        • Yang Y.H.
        • Fu X.B.
        • Sun T.Z.
        • Jiang L.X.
        • Gu X.M.
        bFGF and TGFbeta expression in rat kidneys after ischemic/reperfusional gut injury and its relationship with tissue repair.
        World J Gastroenterol. 2000; 6: 147-149
        • Rusnati M.
        • Presta M.
        Interaction of angiogenic basic fibroblast growth factor with endothelial cell heparan sulfate proteoglycans: biological implications in neovascularization.
        Int J Clin Lab Res. 1996; 26: 15-23