Bioinformatics approach for data management about bone cells grown on substitute materials

Motivation and Objectives Tissue engineering, the research field aimed at finding high technological biomaterials able to restore, maintain, or improve tissue function, concentrates many efforts in the contest of bone and cartilage, due to their possible wide-spread clinical applications. The main target is the design of well performing scaffolds suitable to promote the development of natural tissue in implant conditions, without generating rejection and, hopefully, degrading in vivo at the same rate of tissue formation. Concerning both bone and cartilage, one of the most important research aspects is determining the biochemical and topological factors that induce cell differentiation and tissue ingrowth. The scaffold material composition is crucial and many of them have been already tested, including alginate (Duggal et al., 2009), collagen/chitosan (Ravindran et al., 2012), polycaprolactone (PCL) and hydroxyapatite (HA) (Scaglione et al., 2010), Poly-L-Lactide Acid (PLLA) (Ciapetti et al., 2012), polymethylmethacrylate (BombonatoPrado et al., 2007), bioactive glasses (Leven et al., 2004), carbon nanotubes (Van der Zande et al., 2004), etc. To better evaluate material performance, the biomolecular characterization of the cellular response is becoming a common practice among researchers. Nonetheless, experimental data usually remain sparse in literature: the collection of high-throughput gene expression profiles from samples on different materials could allow data comparisons and formulation of new hypotheses about the effectiveness of bone/cartilage substitute. In this context authors extended the existing OsteoChondroDB database (Viti et al., 2012), which collects data and metadata from microarray gene expression of cells cultured in different conditions onto diverse materials, and allows analyzing differentially expressed genes (DEG) from the available knowledge base. Methods The OsteoChondroDB relies on MySQL database, while the web interface has been developed using php and javascript technologies, and this improved version of the systems is based on the same infrastructure. Manual research has been performed on papers containing biomolecular data about osteochondral tissue developed on different scaffolds. Data have been retrieved from known public repositories such as Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/) and ArrayExpress (http://www.ebi.ac.uk/arrayexpress/), whenever experiments were available, or directly contacting papers authors. The amount of data produced in this field is new, scarce, and variegated, although the importance of biomolecular aspects related to the tissue growth on materials can be of great importance to design improved scaffolds. To exploit the available data in an integrated fashion, the strategy described by Kodama et al. (Kodama et al., 2012) appears useful, because it proposes a multi-species and multi-platform approach for gene expression microarray data meta-analysis. In this way, it is possible to increase the number of evidences, by considering mouse and rat data together with human experiments and by mixing different versions, brands and designs of microarray chips. The information mapping between species can be performed through AILUN system (Chen R et al., 2007), which converts ids of different platforms.

[1]  D. R. Sumner,et al.  Patterns of gene expression in rat bone marrow stromal cells cultured on titanium alloy discs of different roughness. , 2004, Journal of biomedical materials research. Part A.

[2]  W. Kamps,et al.  Evidence Based Selection of Housekeeping Genes , 2007, PloS one.

[3]  A. Butte,et al.  AILUN: reannotating gene expression data automatically , 2007, Nature Methods.

[4]  J. Brinchmann,et al.  Phenotype and gene expression of human mesenchymal stem cells in alginate scaffolds. , 2009, Tissue engineering. Part A.

[5]  G. Passos,et al.  Microarray-based gene expression analysis of human osteoblasts in response to different biomaterials. , 2009, Journal of biomedical materials research. Part A.

[6]  J. Jansen,et al.  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. , 2010, Acta biomaterialia.

[7]  S. Scaglione,et al.  A composite material model for improved bone formation , 2010, Journal of tissue engineering and regenerative medicine.

[8]  Mrignayani Kotecha,et al.  Biomimetic extracellular matrix-incorporated scaffold induces osteogenic gene expression in human marrow stromal cells. , 2012, Tissue engineering. Part A.

[9]  N. Baldini,et al.  Enhancing Osteoconduction of PLLA-Based Nanocomposite Scaffolds for Bone Regeneration Using Different Biomimetic Signals to MSCs , 2012, International journal of molecular sciences.

[10]  Alexander A. Morgan,et al.  Expression-based genome-wide association study links the receptor CD44 in adipose tissue with type 2 diabetes , 2012, Proceedings of the National Academy of Sciences.

[11]  Ivan Merelli,et al.  OsteoChondroDB: a database about biomolecular chondral- bone development in physiological and diseased conditions , 2012 .