Abstract
The two marine inorganic polymers, biosilica (BS), enzymatically synthesized from ortho-silicate, and polyphosphate (polyP), a likewise enzymatically synthesized polymer consisting of 10 to >100 phosphate residues linked by high-energy phosphoanhydride bonds, have previously been shown to display a morphogenetic effect on osteoblasts. In the present study, the effect of these polymers on the differential differentiation of human multipotent stromal cells (hMSC), mesenchymal stem cells, that had been encapsulated into beads of the biocompatible plant polymer alginate, was studied. The differentiation of the hMSCs in the alginate beads was directed either to the osteogenic cell lineage by exposure to an osteogenic medium (mineralization activation cocktail; differentiation into osteoblasts) or to the chondrogenic cell lineage by incubating in chondrocyte differentiation medium (triggering chondrocyte maturation). Both biosilica and polyP, applied as Ca2+ salts, were found to induce an increased mineralization in osteogenic cells; these inorganic polymers display also morphogenetic potential. The effects were substantiated by gene expression studies, which revealed that biosilica and polyP strongly and significantly increase the expression of bone morphogenetic protein 2 (BMP-2) and alkaline phosphatase (ALP) in osteogenic cells, which was significantly more pronounced in osteogenic versus chondrogenic cells. A differential effect of the two polymers was seen on the expression of the two collagen types, I and II. While collagen Type I is highly expressed in osteogenic cells, but not in chondrogenic cells after exposure to biosilica or polyP, the upregulation of the steady-state level of collagen Type II transcripts in chondrogenic cells is comparably stronger than in osteogenic cells. It is concluded that the two polymers, biosilica and polyP, are morphogenetically active additives for the otherwise biologically inert alginate polymer. It is proposed that alginate, supplemented with polyP and/or biosilica, is a suitable biomaterial that promotes the growth and differentiation of hMSCs and might be beneficial for application in 3D tissue printing of hMSCs and for the delivery of hMSCs in fractures, surgically created during distraction osteogenesis.
Highlights
Bone formation is a complex process involving several cell lineages and growth factors, as well as an ordered scaffold, comprising a fibrillar organic network
The results show that the cells, not treated with osteogenic medium, are not stained, irrespective of whether they were exposed to biosilica or to polyP or remained without these polymers (Figure 3A–D)
If the cells/beads are exposed for five days or 10 days to biosilica or polyP (Ca2+ salt), the level of BMP-2 in the chondrogenic lineage increases only up to about 25% of the levels found in the osteogenic lineage (Figure 4B)
Summary
Bone formation is a complex process involving several cell lineages and growth factors, as well as an ordered scaffold, comprising a fibrillar organic network. Human MSCs (hMSCs), discovered in 1968 by Friedenstein [2], have the capacity to readily differentiate into the osteogenic, chondrogenic, adipogenic or myogenic cell lineage, depending on the activation of specific transcription factors. Polysaccharides, allow the fabrication of a variety of biomaterials suitable for tissue engineering, e.g., gels and fibers, and are suitable vehicles for injectable solutions as pastes [16] If those alginates are enriched with biosilica, the fabricated hydrogel has been shown to provide a morphogenetically active scaffold for bone-related SaOS-2 cells in vitro [8]. Biosilica shows osteogenic potential [21] These data have been supported recently [23] using hMSCs. PolyP is known to act as a storage substance of energy, a chelator for metal cations, a phosphate donor for sugars and adenylate kinase and an inducer of apoptosis; in addition, it is involved in mineralization processes of bone tissue (reviewed in [17]). The data show that these two polymers display a morphogenetic effect on both cell lineages
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
