IGF‐I and TGF‐Beta 1 incorporated in a poly(D,L‐lactide) implant coating stimulates osteoblast differentiation and collagen‐1 production but reduces osteoblast proliferation in cell culture

Abstract

Previous in vivo studies revealed a stimulating effect of locally applied IGF-I and TGF-beta1 released from poly(D,L-lactide)-coated titanium implants on rat and porcine fracture healing. The purpose of the present study was to evaluate the effect of IGF-I (5% w/w) and TGF-beta1 (1% w/w) and the carrier PDLLA on osteoblasts in cell culture to improve the understanding of these growth factors. The well-characterized human osteoblast cell line hFOB 1.19 was used in the study. The implants and cells were cocultured in a noncontact manner. The cells were incubated for 10 days in total, and the implants (n = 6 each group and time point) were added for 1 h, 12 h, 24 h, 2 d, 4 d, or 10 d. To analyze a possible effect of the growth factors or the coating, cell proliferation, metabolism, and differentiation were investigated. As an indicator for differentiation the production of collagen I was chosen. All experimental groups showed comparable cell vitality. No change in the pH of the medium was detectable between the analyzed groups. When the effect of the titanium implant and the PDLLA coating were compared with the control culture, no differences in proliferation, metabolic activity, and collagen I production were detectable. The osteoblasts treated with IGF-I and TGF-beta1 released from PDLLA revealed a significantly enhanced collagen I production with a decrease in proliferation and metabolic activity compared to the other groups. No significant differences in collagen I production were seen due to the incubation time points. None of the experimental groups evoked an immunological response on mouse macrophages. In conclusion, the PDLLA-carrier showed no negative effect on osteoblasts, whereas the incorporated growth factors stimulated osteoblast differentiation.

IGF-I and TGF-beta 1 incorporated in a poly(d,l-lactide) implant coating maintain their activity over long-term storage—cell culture studies on primary human osteoblast-like cells

“…Both implant types were able to significantly stimulate the production of procollagen 1 in comparison to the control groups. Previous work using the same application method of IGF-I and TGF-b1 (storage duration: 1 month) showed a comparable effect of the growth factor coated implants on an osteoblast cell line hFOB 1.19 [30]. The cells showed a similar proliferation compared to the controls but a significantly enhanced production of procollagen 1 independently from the incubation time with the implant.…”

Strategies for cell manipulation and skeletal tissue engineering using high-throughput polymer blend formulation and microarray techniques

“…However, comprehensive osteogenic differentiation of the skeletal stem cells into mature osteoblasts requires the presence of key osteogenic growth factors such as BMP-2 [66]. Growth factors including BMP-2, TGF-b1 and IGF-1 have been incorporated into polylactic polymers without loss of biological activity and shown to enhance osteoblast differentiation of cultured human skeletal stem cells [67,68]. On going studies in our groups are focussed on the generation of PLLA/PCL scaffolds with appropriate angiogenic and osteogenic factors capable of temporal delivery.…”

Effects of a Mixture of Growth Factors and Proteins on the Development of the Osteogenic Phenotype in Human Alveolar Bone Cell Cultures

“…(J Histochem Cytochem 56:629-638, 2008) K E Y W O R D S cell culture osteoblasts growth factors cell proliferation alkaline phosphatase mineralization THE TERM growth factor (GF) refers to a class of signaling proteins that stimulate the processes of cell proliferation and/or differentiation in target cells. The induced cellular effects depend on several parameters, which include the (a) concentration of GFs in the extracellular milieu, (b) time and duration of exposure, (c) target cell type and its differentiation state, (d) the expression of specific cell receptors, and (e) the presence of other GFs, which can promote synergistic or antagonistic effects (Giannobile et al 1997;Schmidmaier et al 2003;Chaudhary et al 2004;Huang et al 2005).…”