Injectable in situ-forming pH/thermo-sensitive hydrogel for bone tissue engineering.
We developed a novel pH- and thermo-sensitive hydrogel as a scaffold for autologous bone tissue engineering. We synthesized this polymer by adding pH-sensitive sulfamethazine oligomers (SMOs) to both ends of a thermo-sensitive poly(epsilon-caprolactone-co-lactide)-poly(ethylene glycol)-poly(epsilon-caprolactone-co-lactide) (PCLA-PEG-PCLA) block copolymer, yielding a pH/thermo-sensitive SMO-PCLA-PEG-PCLA-SMO block copolymer. The synthesized block copolymer solution rapidly formed a stable gel under physiological conditions (pH 7.4 and 37 degrees C), whereas it formed a sol at pH 8.0 and 37 degrees C, making it injectable. This pH/thermo-sensitive hydrogel exhibited high biocompatibility in a Dulbecco's modified Eagle's medium extract test. Under physiological conditions, the hydrogel easily encapsulated human mesenchymal stem cells (hMSCs) and recombinant human bone morphogenetic protein-2 (rhBMP-2), with encapsulating efficiencies of about 90% and 85%, respectively. To assay for ectopic bone formation in vivo, we subcutaneously injected a polymer solution containing hMSCs and rhBMP-2 into the back of mice, after which we could observe hMSC differentiation for up to 7 weeks. Histological studies revealed mineralized tissue formation and high levels of alkaline phosphatase activity in the mineralized tissue. Therefore, this pH/thermo-sensitive SMO-PCLA-PEG-PCLA-SMO block copolymer demonstrated potential as an injectable scaffold for bone tissue engineering, with in situ formation capabilities.
Kim
Hea Kyung
HK
Department of Polymer Science & Engineering, Sungkyunkwan University, Suwon, Republic of Korea.
Shim
Woo Sun
WS
Kim
Sung Eun
SE
Lee
Kweon-Haeng
KH
Kang
Eunah
E
Kim
Jong-Ho
JH
Kim
Kwangmeyung
K
Kwon
Ick Chan
IC
Lee
Doo Sung
DS
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D001842:Bone and Bones; D002454:Cell Differentiation; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D010012:Osteogenesis / Q000502:physiology; D011108:Polymers / Q000737:chemistry*; D013696:Temperature; D023822:Tissue Engineering / Q000379:methods*
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D011108:Polymers; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D000469:Alkaline Phosphatase