title: The marine sponge-derived inorganic polymers, biosilica and polyphosphate, as morphogenetically active matrices/scaffolds for the differentiation of human multipotent stromal cells: potential application in 3D printing and distraction osteogenesis.
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.
authors.affiliation: ERC Advanced Investigator Grant Research Group, Institute for Physiological Chemistry, University Medical Center, Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany. wang013@uni-mainz.de.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
authors.affiliation: ERC Advanced Investigator Grant Research Group, Institute for Physiological Chemistry, University Medical Center, Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany. hschroed@uni-mainz.de.
authors.forename: Heinz C
authors.initials: HC
authors.lastname: Schröder
authors.affiliation: ERC Advanced Investigator Grant Research Group, Institute for Physiological Chemistry, University Medical Center, Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany. grebenyu@uni-mainz.de.
authors.forename: Vladislav
authors.initials: V
authors.lastname: Grebenjuk
authors.affiliation: NanotecMARIN GmbH, 55128 Mainz, Germany. helmut-baerbel.Seifert@t-online.de.
authors.forename: Bärbel
authors.initials: B
authors.lastname: Diehl-Seifert
authors.affiliation: Max Planck Institute for Polymer Research, Ackermannweg 10, 55129 Mainz, Germany. volker.mailaender@mpip-mainz.mpg.de.
authors.forename: Volker
authors.initials: V
authors.lastname: Mailänder
authors.affiliation: ERC Advanced Investigator Grant Research Group, Institute for Physiological Chemistry, University Medical Center, Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany. steffen@uni-mainz.de.
authors.forename: Renate
authors.initials: R
authors.lastname: Steffen
authors.affiliation: ERC Advanced Investigator Grant Research Group, Institute for Physiological Chemistry, University Medical Center, Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany. schlossm@uni-mainz.de.
authors.forename: Ute
authors.initials: U
authors.lastname: Schloßmacher
authors.affiliation: ERC Advanced Investigator Grant Research Group, Institute for Physiological Chemistry, University Medical Center, Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany. wmueller@uni-mainz.de.
authors.forename: Werner E G
authors.initials: WE
authors.lastname: Müller
mesh_terms: D000464:Alginates / Q000737:chemistry; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D024042:Collagen Type I / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D019857:Osteogenesis, Distraction / Q000379:methods; D011108:Polymers / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D011122:Polyphosphates / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D011161:Porifera / Q000737:chemistry*; D012822:Silicon Dioxide / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D000464:Alginates; D055396:Bone Morphogenetic Protein 2; D024042:Collagen Type I; D024043:Collagen Type II; D006603:Hexuronic Acids; D011108:Polymers; D011122:Polyphosphates; D012822:Silicon Dioxide; D020723:Glucuronic Acid; D000469:Alkaline Phosphatase