Tissue Engineering of Flexor Tendons: Optimization of Tenocyte Proliferation Using Growth Factor Supplementation
- 1 July 2006
- journal article
- research article
- Published by Mary Ann Liebert Inc in Tissue Engineering
- Vol. 12 (7), 1937-1943
- https://doi.org/10.1089/ten.2006.12.1937
Abstract
A significant problem in flexor tendon repair is the lack of suitable graft material for reconstruction. The ex vivo production of flexor tendon graft constructs requires the expansion of primary cells. Growth factors, such as platelet-derived growth factor-BB (PDGF-BB), insulin-like growth factor-1 (IGF-1), and basic fibroblast growth factor (bFGF), are known to promote tendon healing and tendon cell proliferation. The purpose of these experiments was to optimize tenocyte proliferation in 3 tendon cell populations using growth factor supplementation. Cells of the synovial sheath, epitenon, and endotenon were isolated from rabbit flexor digitorum profundus tendons and maintained in culture. Cell cultures were supplemented with IGF-1, PDGF-BB, and bFGF alone and in combination. The conditions used for individual growth factor supplementation were IGF-1 (10, 50, and 100 ng/mL), PDGF-BB (1, 10, and 50 ng/mL), and bFGF (0.5, 1, and 5 ng/mL). The conditions used for combinations of growth factors were IGF-1 + PDGF-BB (50 + 10 and 100 + 50 ng/mL, respectively) and IGF-1 + PDGF-BB+ bFGF (50 + 10 + 1; 50 + 10 + 5; 100 + 50 + 1; and 100 + 50 + 5 ng/mL, respectively). For all 3 tendon cell populations, proliferation at 72 h was greater in the presence of individual growth factors as compared to controls. With PDGF-BB (50 ng/mL) supplementation, mean absorbance values increased 97% (0.57 to 1.13) in S cells, 37% (0.51 to 0.70) in E cells, and 33% (0.33 to 0.44) in T cells ( p < 0.001). In addition, a synergistic effect was observed. The combination of growth factors resulted in greater proliferation as compared to maximal doses of individual growth factors. In cultures supplemented with IGF-1 (100 ng/mL) +PDGF-BB (50 ng/mL), mean absorbance increased 114% (0.57 to 1.22) in S cells, 63% (0.51 to 0.831) in E cells, and 47% (0.33 to 0.48) in T cells ( p < 0.001). IGF-1 (100 ng/mL) + PDGF-BB (50 ng/mL) + bFGF (5 ng/mL) resulted in the greatest amount of cell proliferation for all 3 tendon cell populations. The mean absorbances increased 251% in S cells, 98% in E cells, and 106% in T cells ( p < 0.001). In summary, IGF-1, PDGF-BB, and bFGF can be used in combination to maximize tenocyte proliferation. Synergism among growth factors may provide a means to facilitate tendon engineering.Keywords
This publication has 28 references indexed in Scilit:
- Engineering of Functional TendonTissue Engineering, 2004
- Insulin‐like growth factor‐I is expressed by avian flexor tendon cellsJournal of Orthopaedic Research, 2000
- Effects of basic fibroblast growth factor (bFGF) on early stages of tendon healing: A rat patellar tendon modelActa Orthopaedica, 2000
- Molecular studies in flexor tendon wound healing: The role of basic fibroblast growth factor gene expressionThe Journal of Hand Surgery, 1998
- Similar effects of recombinant human insulin‐like growth factor‐I and II on cellular activities in flexor tendons of young rabbits: Experimental studies in vitroJournal of Orthopaedic Research, 1997
- Human Composite Flexor Tendon AllograftsJournal of Hand Surgery (European Volume), 1996
- Growth factors and canine flexor tendon healing: Initial studies in uninjured and repair modelsThe Journal of Hand Surgery, 1995
- Recombinant human insulin‐like growth factor‐I stimulates in vitro matrix synthesis and cell proliferation in rabbit flexor tendonJournal of Orthopaedic Research, 1991
- Cell populations of tendon: A simplified method for isolation of synovial cells and internal fibroblasts: Confirmation of origin and biologic propertiesJournal of Orthopaedic Research, 1988
- Angiogenic FactorsScience, 1987