Bone tissue engineering : biomimetic structures for human osteoprogenitor growth

In vitro and in vivo approaches to investigate the ability to generate biomimetic scaffolds for bone tissue engineering included the use of 1) surface-modification of an biodegradable polymer scaffold with GRGDS peptide, fibronectin (FN), 2) Saos-2 'retentate' extracts (BMP's), 3) recombinant human pleiotrophin (rhPTN) and, 4) recombinant human bone morphogenetic protein-2 (rhBMP-2). In addition, the potential of growth factor encapsulation and gene therapy to deliver growth factors to modulate human osteoprogenitors adhesion and differentiation was examined. Human osteoprogenitors were shown to adhere, differentiation and to mineralised on FN and GRGDS coupled polymer films as well as on three-dimensional (3-D) biodegradable scaffolds indicating the potential to generate porous scaffolds with the ability to mimic the biological microenvironments for cell growth. Saos-2 cell 'retentate' extract, which contains a mixture of BMP's, stimulated human osteoprogenitor adhesion, growth and differentiation on poly(-lactic acid co÷glycolic acid) (PLGA) (75:25) porous scaffolds. 3-D biomimetic structures adsorbed with rhPTN maintained the ability to modulate human osteoprogenitor activity resulting in new cartilage and bone matrix formation both in vitro and in vivo. Human BMP-2 gene adenoviral transfer into human bone marrow stromal cells confirmed the possibility of using gene therapy to engineer bone tissue. Furthermore, rhBMP-2 encapsulated within PLA porous scaffolds by a supercritical fluid mixing method, stimulated C2C12 cell differentiation and promoted human osteoprogenitor proliferation, differentiation as well as new cartilage and bone formation on 3-D PLA scaffolds in vivo. In conclusion, these studies indicates that the ability to generate osteoinductive and osteoconductive biomimetic scaffold using biodegradable polymers in combination with osteogenic growth factors to create a biomimetic microenvironment for human osteoprogenitor growth and to generate templates for the development of a living tissue substitute for bone.