Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.biomaterials.2006.06.019
Title: Mineralization capacity of Runx2/Cbfa1-genetically engineered fibroblasts is scaffold dependent
Authors: Phillips, J.E.
Hutmacher, D.W. 
Guldberg, R.E.
García, A.J.
Keywords: Bone tissue engineering
Fibroblast
Osteoblast
Osteogenic differentiation
Runx2/Cbfa1
Scaffold
Issue Date: Nov-2006
Source: Phillips, J.E., Hutmacher, D.W., Guldberg, R.E., García, A.J. (2006-11). Mineralization capacity of Runx2/Cbfa1-genetically engineered fibroblasts is scaffold dependent. Biomaterials 27 (32) : 5535-5545. ScholarBank@NUS Repository. https://doi.org/10.1016/j.biomaterials.2006.06.019
Abstract: Development of tissue-engineered constructs for skeletal regeneration of large critical-sized defects requires the identification of a sustained mineralizing cell source and careful optimization of scaffold architecture and surface properties. We have recently reported that Runx2-genetically engineered primary dermal fibroblasts express a mineralizing phenotype in monolayer culture, highlighting their potential as an autologous osteoblastic cell source which can be easily obtained in large quantities. The objective of the present study was to evaluate the osteogenic potential of Runx2-expressing fibroblasts when cultured in vitro on three commercially available scaffolds with divergent properties: fused deposition-modeled polycaprolactone (PCL), gas-foamed polylactide-co-glycolide (PLGA), and fibrous collagen disks. We demonstrate that the mineralization capacity of Runx2-engineered fibroblasts is scaffold dependent, with collagen foams exhibiting ten-fold higher mineral volume compared to PCL and PLGA matrices. Constructs were differentially colonized by genetically modified fibroblasts, but scaffold-directed changes in DNA content did not correlate with trends in mineral deposition. Sustained expression of Runx2 upregulated osteoblastic gene expression relative to unmodified control cells, and the magnitude of this expression was modulated by scaffold properties. Histological analyses revealed that matrix mineralization co-localized with cellular distribution, which was confined to the periphery of fibrous collagen and PLGA sponges and around the circumference of PCL microfilaments. Finally, FTIR spectroscopy verified that mineral deposits within all Runx2-engineered scaffolds displayed the chemical signature characteristic of carbonate-containing, poorly crystalline hydroxyapatite. These results highlight the important effect of scaffold properties on the capacity of Runx2-expressing primary dermal fibroblasts to differentiate into a mineralizing osteoblastic phenotype for bone tissue engineering applications. © 2006 Elsevier Ltd. All rights reserved.
Source Title: Biomaterials
URI: http://scholarbank.nus.edu.sg/handle/10635/67159
ISSN: 01429612
DOI: 10.1016/j.biomaterials.2006.06.019
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