OGP functionalized phenylalanine-based poly(ester urea) for enhancing osteoinductive potential of human mesenchymal stem cells.
Amino acid-based poly(ester urea)s (PEU) are high modulus, resorbable polymers with many potential uses, including the surgical repair of bone defects. In vitro and in vivo studies have previously shown that phenylalanine-based PEUs have nontoxic hydrolytic byproducts and tunable degradation times. Phenylalanine PEUs (poly(1-PHE-6)) have been further modified by tethering osteogenic growth peptide (OGP) to tyrosine-based monomer subunits. These OGP-tethered PEUs have been fabricated into porous scaffolds and cultured in vitro to examine their effect on differentiation of human mesenchymal stem cells (hMSCs) toward the osteogenic lineage. The influence of tethered OGP on the hMSC proliferation and differentiation profile was measured using immunohistochemistry, biochemistry, and quantitative real time polymerase chain reaction (qRT-PCR). In vitro data indicated an enhanced expression of BSP by 130-160% for hMSCs on OGP-tethered scaffolds compared to controls. By 4 weeks, there was a significant drop (60-85% decrease) in BSP expression on OGP-functionalized scaffolds, which is characteristic of osteogenic differentiation. ALP and OSC expression was significantly enhanced for OGP-functionalized scaffolds by week 4, with values reaching 145% and 300% greater, respectively, compared to nonfunctionalized controls. In vivo subcutaneous implantation of poly(1-PHE-6) scaffolds revealed significant tissue-scaffold integration, as well as the promotion of both osteogenesis and angiogenesis.
Gina M
GM
Policastro
Fei
F
Lin
Laura A
LA
Smith Callahan
‡Calhoun Research Laboratory, Akron General Medical Center, Akron, Ohio 44307, United States.
Andrew
A
Esterle
§Akron Polymer Systems, Akron, Ohio 44308, United States.
Matthew
M
Graham
‡Calhoun Research Laboratory, Akron General Medical Center, Akron, Ohio 44307, United States.
Kimberly
K
Sloan Stakleff
Matthew L
ML
Becker
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D048091:Guided Tissue Regeneration; D006657:Histones / Q000737:chemistry; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D010012:Osteogenesis; D010649:Phenylalanine / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry*; D014508:Urea / Q000031:analogs & derivatives* / Q000737:chemistry
D006657:Histones; D036341:Intercellular Signaling Peptides and Proteins; D011091:Polyesters; C492424:poly(ester-urea); C074533:osteogenic growth peptide; D010649:Phenylalanine; D014508:Urea