The use of injectable, thermosensitive poly(organophosphazene)-RGD conjugates for the enhancement of mesenchymal stem cell osteogenic differentiation.
An injectable and thermosensitive poly(organophosphazene)-RGD conjugate to enhance functionality was synthesized by a covalent amide linkage between a cell adhesion peptide, GRGDS and carboxylic acid-terminated poly(organophosphazene). The aqueous solutions of synthesized poly(organophosphazene)-GRGDS conjugates existed in an injectable fluid state at room temperature and immediately formed a hydrogel at body temperature. The rabbit mesenchymal stem cells (rMSCs) on the polymer-GRGDS conjugate (conjugate 1-2, 0.05 mol fraction as GRGDS) hydrogel constructs using an injection method into a nude mouse were proved to express markers at mRNA level for all stages towards osteogenesis and mainly a sharp increase of osteocalcin (OCN, a typical late osteogenic differentiation marker) levels at 4th week post-induction indicated that the maturation process has started within this period. By histological and immunohistochemical evaluations, significantly high mineralization level by calcium contents was detected qualitatively and collagen type I (Col I), a major characteristic marker protein, was mainly and highly expressed by the rMSCs cultivated in the polymer-GRGDS conjugate hydrogel constructs formed into the nude mouse. The results suggest that the poly(organophosphazene)-GRGDS conjugate to enhance biofunctionality hold a promise for cell delivery material to induce osteogenic differentiation of MSC for enhancing ectopic bone formation.
Chun
Changju
C
Division of Life Science, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea.
Lim
Hye Jin
HJ
Hong
Ki-Yun
KY
Park
Keun-Hong
KH
Song
Soo-Chang
SC
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry / Q000378:metabolism*; D007150:Immunohistochemistry; D009682:Magnetic Resonance Spectroscopy; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D008954:Models, Biological; D009842:Oligopeptides / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000737:chemistry*; D010012:Osteogenesis / Q000502:physiology*; D011108:Polymers / Q000737:chemistry*; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023822:Tissue Engineering / Q000379:methods*
D009842:Oligopeptides; D009943:Organophosphorus Compounds; D011108:Polymers; C515246:poly(organophosphazene); D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C047981:arginyl-glycyl-aspartic acid