New regenerative materials and approaches need to be assessed through reliable and comparable methods for rapid translation to the clinic. There is a considerable need for proven in vitro assays that are able to reduce the burden on animal testing, by allowing assessment of biomaterial utility predictive of the results currently obtained through in vivo studies. The purpose of this multicentre review was to investigate the correlation between existing in vitro results with in vivo outcomes observed for a range of biomaterials. Members from the European consortium BioDesign, comprising 8 universities in a European multicentre study, provided data from 36 in vivo studies and 47 in vitro assays testing 93 different biomaterials. The outcomes of the in vitro and in vivo experiments were scored according to commonly recognised measures of success relevant to each experiment. The correlation of in vitro with in vivo scores for each assay alone and in combination was assessed. A surprisingly poor correlation between in vitro and in vivo assessments of biomaterials was revealed indicating a clear need for further development of relevant in vitro assays. There was no significant overall correlation between in vitro and in vivo outcome. The mean in vitro scores revealed a trend of covariance to in vivo score with 58 %. The inadequacies of the current in vitro assessments highlighted here further stress the need for the development of novel approaches to in vitro biomaterial testing and validated pre-clinical pipelines.
Cell support function as well as cell proliferation on highly porous Bioglass(R)-derived glass-ceramic scaffolds (designed for bone tissue engineering) have been assessed in vitro using osteoblast-like cells (MG 63) cultured for up to 6 days. The biodegradation and mechanical stability of the scaffolds in the cell-culture medium have also been investigated. It was found that the scaffolds had excellent cell supporting ability, with cells effectively infiltrating into and surviving at the center of the scaffolds. A quantitative study using the AlamarBlue assay revealed that the proliferation of cells on the glass-ceramic materials was comparable to that on the noncrystallized Bioglass. While the crystalline phase in the glass-ceramic scaffolds transformed into a biodegradable amorphous calcium phosphate phase during cell culture, the mechanical strength of the scaffolds was maintained when compared with that of scaffolds incubated in simulated body fluid or immersed in cell-free culture medium. It is believed that the attached cells and collagen secreted by cells could fill the micropores and microcracks on the surface of the foam struts, thus contributing to the mechanical stability of the degrading scaffolds. In summary, the developed glass-ceramic scaffolds possess the most essential features of a scaffold for bone tissue engineering: they are capable to support and foster relevant cells, able to provide temporary mechanical function, and biodegradable.
Phosphate-based fibres of the generic composition (CaO)0.46-(Na2O)n-(Fe2O3)y-(P2O5)0.50 have been evaluated, in vitro, as three dimensional scaffolds for tissue engineering of the hard-soft tissue interface by assessing the fibre solubility and growth and functional gene expression of human cells. Primary human osteoblasts and fibroblasts were seeded onto scaffolds and maintained in culture for up to 21 days. Fluorescent immunolabeling revealed the spread cell morphology and significant proliferation pattern on these fibres, particularly on the 3 mol% Fe2O3-containing formulation. Real-time quantitative Polymerase Chain Reaction (rtQ-PCR) analysis of gene expression using TaqMan Probes was preformed and it has been established that committed cell differentiation was maintained by both cell types, and was strongly related to the 3 mol% Fe2O3 glass composition. These novel, readily manufactured, soluble glass fibres offer a biocompatible and biochemically favourable alternative in the search for suitable degradable materials used in Tissue Engineering.
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