The Effects of Exogenous Basic Fibroblast Growth Factor on Intrasynovial Flexor Tendon Healing in a Canine Model

Thomopoulos, Stavros; Kim, Hyun Min; Das, Rosalina; Silva, Matthew J.; Sakiyama‐Elbert, Shelly E.; Amiel, David; Gelberman, Richard H.

doi:10.2106/jbjs.i.01601

Cited by 87 publications

(100 citation statements)

References 31 publications

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“…The reasons for the opposite effect of FGF signalling on limb mesodermal cells between the chick and mouse models remain unclear. However, these results are consistent with an absence or deleterious effect of FGF on tendon marker expression in 2D-culture systems of various stem cells, including mouse embryonic tendon progenitors (Brown et al, 2014), mouse mesenchymal stem cells (Havis et al, 2014), canine tendon fibroblasts (Thomopoulos et al, 2010), human amniotic fluid stem cells or adipose-derived stem cells (Goncalves et al, 2013). Consistent with the FGF tenogenic function during chick tendon development, a clear beneficial effect of FGF has been described during tendon repair in a chick digital tendon injury model.…”

Section: Tgfβ2 Maintains Scx Tnmd and Thbs2 Expression In Immobilisesupporting

confidence: 76%

TGFβ and FGF promote tendon progenitor fate and act downstream of muscle contraction to regulate tendon differentiation during chick limb development

et al. 2016

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The molecular programme underlying tendon development has not been fully identified. Interactions with components of the musculoskeletal system are important for limb tendon formation. Limb tendons initiate their development independently of muscles; however, muscles are required for further tendon differentiation. We show that both FGF/ERK MAPK and TGFβ/SMAD2/3 signalling pathways are required and sufficient for SCX expression in chick undifferentiated limb cells, whereas the FGF/ERK MAPK pathway inhibits Scx expression in mouse undifferentiated limb mesodermal cells. During differentiation, muscle contraction is required to maintain SCX, TNMD and THBS2 expression in chick limbs. The activities of FGF/ERK MAPK and TGFβ/SMAD2/3 signalling pathways are decreased in tendons under immobilisation conditions. Application of FGF4 or TGFβ2 ligands prevents SCX downregulation in immobilised limbs. TGFβ2 but not FGF4 prevent TNMD and THBS2 downregulation under immobilisation conditions. We did not identify any intracellular crosstalk between both signalling pathways in their positive effect on SCX expression. Independently of each other, both FGF and TGFβ promote tendon commitment of limb mesodermal cells and act downstream of mechanical forces to regulate tendon differentiation during chick limb development.

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Section: Tgfβ2 Maintains Scx Tnmd and Thbs2 Expression In Immobilisesupporting

confidence: 76%

TGFβ and FGF promote tendon progenitor fate and act downstream of muscle contraction to regulate tendon differentiation during chick limb development

et al. 2016

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“…Utilization of sutures may drive the repair to the inner continuum of the tendon stumps and expedite healing with increased repair strength. Past studies employed coating of standard synthetic polymeric sutures with growth factor doped gelatin or growth factor added scaffolds (generally fibrin) [12, 13]. These modifications are reported to achieve some success in the flexor tendon repair.…”

Section: Introductionmentioning

confidence: 99%

Heparinized collagen sutures for sustained delivery of PDGF-BB: Delivery profile and effects on tendon-derived cells In-Vitro

et al. 2016

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Suturing is the standard of repair for lacerated flexor tendons. Past studies focused on delivering growth factors to the repair site by incorporating growth factors to nylon sutures which are commonly used in the repair procedure. However, conjugation of growth factors to nylon or other synthetic sutures is not straightforward. Collagen holds promise as a suture material by way of providing chemical sites for conjugation of growth factors. On the other hand, collagen also needs to be reconstituted as a mechanically robust thread that can be sutured. In this study, we reconstituted collagen solutions as suturable collagen threads by using linear electrochemical compaction. Prolonged release of PDGF-BB (Platelet derived growth factor-BB) was achieved by covalent bonding of heparin to the collagen sutures. Tensile mechanical tests of collagen sutures before and after chemical modification indicated that the strength of sutures following chemical conjugation stages was not compromised. Strength of lacerated tendons sutured with epitendinous collagen sutures (11.2 ± 0.7 N) converged to that of the standard nylon suture (14.9 ± 2.9 N). Heparin conjugation of collagen sutures didn’t affect viability and proliferation of tendon-derived cells and prolonged the PDGF-BB release up to 15 days. Proliferation of cells seeded on PDGF-BB incorporated collagen sutures was about 50% greater than those seeded on plain collagen sutures. Collagen that is released to the media by the cells increased by 120% under the effects of PDGF-BB and collagen production by cells was detectable by histology as of day 21. Addition of PDGF-BB to collagen sutures resulted in a moderate decline in the expression of the tendon-associated markers scleraxis, collagen I, tenomodulin, and COMP; however, expression levels were still greater than the cells seeded on collagen gel. The data indicate that the effects of PDGF-BB on tendon-derived cells mainly occur through increased cell proliferation and that longer term studies are needed to confirm associated genes.

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“…Thomopoulos et al showed that exogenous delivery of FGF and PDGF led to improved tendon strength and healing in a canine model. 37,38 Using an extended delivery vehicle similar to what Thomopoulos described, we could study the effects of growth factors on the healing and incorporation of these constructs.…”

mentioning

confidence: 99%

Human Flexor Tendon Tissue Engineering: Decellularization of Human Flexor Tendons Reduces Immunogenicity In Vivo

Raghavan

Woon

Kraus

et al. 2012

Tissue Engineering Part A

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The Effects of Exogenous Basic Fibroblast Growth Factor on Intrasynovial Flexor Tendon Healing in a Canine Model

Cited by 87 publications

References 31 publications

TGFβ and FGF promote tendon progenitor fate and act downstream of muscle contraction to regulate tendon differentiation during chick limb development

TGFβ and FGF promote tendon progenitor fate and act downstream of muscle contraction to regulate tendon differentiation during chick limb development

Heparinized collagen sutures for sustained delivery of PDGF-BB: Delivery profile and effects on tendon-derived cells In-Vitro

Human Flexor Tendon Tissue Engineering: Decellularization of Human Flexor Tendons Reduces Immunogenicity In Vivo

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