Genetic profiling of osteoblast-like cells cultured on a novel bone reconstructive material, consisting of poly-L-lactide, carbon nanotubes and microhydroxyapatite, in the presence of bone morphogenetic protein-2.
In bone tissue engineering composite materials have been introduced, combining a degradable polymer matrix with, for instance, carbon nanotubes (CNTs) to improve mechanical properties or with microhydroxyapatite (μHA) to improve osteoconduction. The addition of bone morphogenetic protein-2 (BMP-2) can further improve the biological response to the material. However, the influence of such an elaborate composite formation on osteoprogenitor cells is unknown. To examine this, rat bone marrow (RBM) cells were cultured on porous poly-L-lactic acid and composite scaffolds, with or without added BMP-2. Cell proliferation and differentiation were studied using DNA, alkaline phosphatase and scanning electron microscopic analysis. Further, genetic profiles were examined by microarray investigation. Results showed that the composite scaffold had no significant effect on the proliferation of RBM cells, but indicated a negative effect on cell differentiation. The addition of BMP-2 also had no significant effect on the proliferation of RBM cells, but differentiation towards the osteogenic lineage was confirmed. In the arrays results, the addition of BMP-2 alone led to the expression of genes involved in (minor) inflammation. The composite scaffold, and even more distinctly the combination of the composite scaffold with BMP-2, led to the expression of genes, based on gene ontology, connected to tumorigenesis. Therefore, CNT- and μHA-containing composite materials are not recommended as a bone restorative material.
van der Zande
Meike
M
Department of Biomaterials, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Walboomers
X Frank
XF
Brännvall
Mathias
M
Olalde
Beatriz
B
Jurado
Maria J
MJ
Alava
J Iñaki
JI
Jansen
John A
JA
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D017886:Durapatite / Q000494:pharmacology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D019344:Lactic Acid / Q000494:pharmacology*; D008297:Male; D037742:Nanotubes, Carbon / Q000737:chemistry*; D010006:Osteoblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D011091:Polyesters; D011108:Polymers / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D054457:Tissue Scaffolds / Q000737:chemistry
D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D037742:Nanotubes, Carbon; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); D004247:DNA; D017886:Durapatite; D000469:Alkaline Phosphatase