Effect of basic fibroblast growth factor on the healing of defects in the canine anterior cruciate ligament

Kobayashi, Daisuke; Kurosaka, Masahiro; Yoshiya, Shinichi; Mizuno, Kosaku

doi:10.1007/s001670050049

Cited by 101 publications

(71 citation statements)

References 24 publications

(35 reference statements)

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“…Previous studies in the rat model which only assessed an early time point (12 days) used avulsion of MCL at the tibia as an end point, making this model unrealistic [32] for clinically useful investigations. Finally, it is clear that the discrepancies between past studies and the current study suggest that cytokine studies are of limited clinical usefulness if they do not include the simultaneous evaluation of both biomechanical and physiologic properties [3,17,25,26].…”

Section: Discussionmentioning

confidence: 99%

Collagen expression and biomechanical response to human recombinant transforming growth factor beta (rhTGF‐β2) in the healing rabbit MCL

Spindler

Dawson

Stahlman

et al. 2002

Journal Orthopaedic Research

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We investigated biomechanical and collagen expression in a healing bilateral rabbit medial collateral ligament (MCL) model to human recombinant transforming growth factor beta (rhTGF‐β2) at three and six weeks. Each rabbit had rhTGF‐β2 in a bioabsorbable pellet administered in one side, with the contralateral side serving as control (no rhTGF‐β2). All MCL healed with rhTGF‐β2 producing a profoundly increased scar mass at three weeks which decreased in size toward control at six weeks. In‐situ hybridization demonstrated collagen expression (type I and III) no different than control at three weeks, but by six weeks elevated expression of type I was seen. Biomechanical analysis at three weeks showed no effect of rhTGF‐β2 on structural properties. However, at six weeks rhTGF‐β2 significantly inhibited both the maximum load (p < 0.05) and energy absorbed (p < 0.05) with no change in stiffness. Despite increased type I collagen expression and profound increase in early scar mass, rhTGF‐β2 did not improve the structural properties. Whether the dose or mode of delivery is responsible for decline in structural properties cannot be determined in this design. We hypothesize investigations of healing ligaments to cytokines should have biologic and biomechanical properties correlated in the same study at a minimum of two time points. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.

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Section: Discussionmentioning

confidence: 99%

Collagen expression and biomechanical response to human recombinant transforming growth factor beta (rhTGF‐β2) in the healing rabbit MCL

Spindler

Dawson

Stahlman

et al. 2002

Journal Orthopaedic Research

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“…Many investigators in previous studies have tried to increase the rate of new blood vessel formation to repair or reconstruct damaged ligaments and tendons. Kobayashi et al 26 indicated that enhanced neovascularization and formation of granulation tissue induced the healing of a partially injured ACL with growth factor. A sheep study by Yoshikawa et al 27 using a VEGF solution demonstrated that newly formed vessels and infiltrative fibroblasts were more abundant in tendons that had been soaked in VEGF solution prior to being grafted into a ruptured ACL than in tendons that had been soaked in PBS.…”

Section: Angiogenesis After Implantation In Vivomentioning

confidence: 99%

Increase in cell migration and angiogenesis in a composite silk scaffold for tissue‐engineered ligaments

Seo

Yoon

Song

et al. 2009

Journal Orthopaedic Research

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The purpose of this study was to evaluate the biocompatibility of silk and collagen-hyaluronan (HA) in vitro by assessing anterior cruciate ligament (ACL) cell and T-lymphocyte cultures on scaffolds. The use of composite scaffolds as artificial ligaments in ACL reconstruction and their effects on angiogenesis were evaluated in vivo. The silk scaffold was knitted by hand and dry coated with collagen-HA, whereas the composite silk scaffold was made by covering a silk scaffold with a lyophilized collagen-HA substrate. The initial attachment and proliferation of human ACL cells on the composite silk scaffold was superior to the attachment and proliferation observed on the silk scaffold. The immune response was higher in both scaffolds after 72 h ( p < 0.05) compared with the control culture condition without scaffolding, as assessed by T-lymphocyte cultures in vitro. There was no significant difference in the immune response in vitro between the silk and composite silk scaffolds. Silk and composite silk scaffolds were implanted as artificial ligaments in ACLs removed from the knees of dogs, and they were harvested 6 weeks after implantation. On gross examination, the onset of an inflammatory tissue reaction, such as synovitis, was seen in both the silk scaffold and the composite silk scaffold groups. An histological evaluation of the artificial ligament implants revealed the presence of monocytes in the silk composite scaffold and the absence of giant cells in all cases. MT staining in the composite silk scaffold-grafted group showed granulation tissue consisting of fibroblasts, lymphocytes, monocytes, and collagen fibers. In addition, CD31 staining revealed the formation of new blood vessels. On the other hand, no reparative tissues, such as blood vessels, collagen, and cells, were observed in the silk scaffold-grafted group. These results suggest that the lyophilized collagen-HA substrate is biocompatible in vitro and enhances new blood vessel and cell migration in vivo. ß

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“…bFGF-impregnated pellet using hydroxyethyl methacrylate stimulates initial remodeling process with a decreased number of cells and better orientation of the collagen fibers in a canine anterior cruciate ligament (ACL) injury model [30]. A poly-L-lactic acid braid scaffold combined with bFGF and a gelatin hydrogel results in enhanced mechanical strength and collagen production of regenerated ACL tissue in a rabbit model [3].…”

Section: Discussionmentioning

confidence: 99%

Combined use of bFGF and GDF-5 enhances the healing of medial collateral ligament injury

Saiga

Furumatsu

Yoshida

et al. 2010

Biochemical and Biophysical Research Communications

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Basic fibroblast growth factor (bFGF) and growth and differentiation factor (GDF)-5 stimulate the healing of medial collateral ligament (MCL) injury. However, the effect of isolated and combined use of bFGF/GDF-5 remains still unclear. We investigated cellular proliferation and migration responding to bFGF/GDF-5 using rabbit MCL fibroblasts. Rabbit MCL injury was treated by bFGF and/or GDF-5 with peptide hydrogels. Gene expression and deposition of collagens in healing tissues were evaluated. bFGF/GDF-5 treatment additively enhanced cell proliferation and migration. bFGF/GDF-5 hydrogels stimulated Col1a1 expression without increasing Col3a1 expression. Combined use of bFGF/GDF-5 stimulated type I collagen deposition and the reorganization of fiber alignment, and induced better morphology of fibroblasts in healing MCLs. Our study indicates that combined use of bFGF/GDF-5 might enhance MCL healing by increasing proliferation and migration of MCL fibroblasts, and by regulating collagen synthesis and connective fiber alignment.

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Effect of basic fibroblast growth factor on the healing of defects in the canine anterior cruciate ligament

Cited by 101 publications

References 24 publications

Collagen expression and biomechanical response to human recombinant transforming growth factor beta (rhTGF‐β2) in the healing rabbit MCL

Collagen expression and biomechanical response to human recombinant transforming growth factor beta (rhTGF‐β2) in the healing rabbit MCL

Increase in cell migration and angiogenesis in a composite silk scaffold for tissue‐engineered ligaments

Combined use of bFGF and GDF-5 enhances the healing of medial collateral ligament injury

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