An injectable cationic hydrogel electrostatically interacted with BMP2 to enhance in vivo osteogenic differentiation of human turbinate mesenchymal stem cells

• Published in: Materials Science & Engineering C Vol. 103; p. 109853
• Main Authors: Kim, Mal Geum, Kang, Tae Woong, Park, Joon Yeong, Park, Seung Hun, Ji, Yun Bae, Ju, Hyeon Jin, Kwon, Doo Yeon, Kim, Young Sik, Kim, Sung Won, Lee, Bong, Choi, Hak Soo, Lee, Hai Bang, Kim, Jae Ho, Lee, Bun Yeoul, Min, Byoung Hyun, Kim, Moon Suk
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2019; Elsevier BV
• Subjects: Adult; Alizarin; Animals; Biocompatibility; Biomedical materials; Bone; Bone Morphogenetic Protein 2 - metabolism; Cations; Collagen; Differentiation (biology); Electrostatic interaction; Female; Fluorescence; Formulations; Gene expression; Heterografts; Human turbinate mesenchymal stem cells; Humans; Hydrogels; Hydrogels - chemistry; Hydrogels - pharmacology; Infrared imaging; Injectable hydrogel depot; Macrophages; Materials science; Mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Mesenchyme; Mice; Osteocalcin; Osteogenesis - drug effects; Osteogenic differentiation; Osteonectin; Osteopontin; Polyelectrolytes; Polyethylene glycol; Polylactic acid; Static Electricity; Stem Cell Transplantation; Stem cells; Surgical implants; Turbinates - cytology; Turbinates - metabolism; Injectable hydrogel depot; Human turbinate mesenchymal stem cells; Osteogenic differentiation; Electrostatic interaction
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2019.109853

We have designed and characterized an injectable, electrostatically bonded, in situ–forming hydrogel system consisting of a cationic polyelectrolyte [(methoxy)polyethylene glycol-b-(poly(ε-caprolactone)-ran-poly(L-lactic acid)] (MP) copolymer derivatized with an amine group (MP-NH2) and anionic BMP2. To the best of our knowledge, there have been hardly any studies that have investigated electrostatically bonded, in situ–forming hydrogel systems consisting of MP-NH2 and BMP2, with respect to how they promote in vivo osteogenic differentiation of human turbinate mesenchymal stem cells (hTMSCs). Injectable formulations almost immediately formed an electrostatically loaded hydrogel depot containing BMP2, upon injection into mice. The hydrogel features and stability of BMP2 inside the hydrogel were significantly affected by the electrostatic attraction between BMP2 and MP-NH2. Additionally, the time BMP2 spent inside the hydrogel depot was prolonged in vivo, as evidenced by in vivo near-infrared fluorescence imaging. Biocompatibility was demonstrated by the fact that hTMSCs survived in vivo, even after 8 weeks and even though relatively few macrophages were in the hydrogel depot. The osteogenic capacity of the electrostatically loaded hydrogel implants containing BMP2 was higher than that of a hydrogel that was simply loaded with BMP2, as evidenced by Alizarin Red S, von Kossa, and hematoxylin and eosin staining as well as osteonectin, osteopontin, osteocalcin, and type 1α collagen mRNA expression. The results confirmed that our injectable, in situ–forming hydrogel system, electrostatically loaded with BMP2, can enhance in vivo osteogenic differentiation of hTMSCs. •An injectable, electrostatically bonded, in situ–forming hydrogel system consisting of a cationic polyelectrolyte copolymer derivatized with an amine group and anionic BMP2 was prepared.•The hydrogel features and stability of BMP2 inside the hydrogel were significantly affected by the electrostatic attraction between BMP2 and cationic polyelectrolyte copolymer.•The electrostatically loaded hydrogel enhanced osteogenic differentiation of human turbinate mesenchymal stem cells better than one with simple loading of BMP2.