Injectable in situ-forming pH/thermo-sensitive hydrogel for bone tissue engineering

Hea Kyung Kim, Woo Sun Shim, Sung Eun Kim, Kweon Haeng Lee, Eunah Kang, Jong Ho Kim, Kwangmeyung Kim, Ick Chan Kwon, Doo Sung Lee

Research output: Contribution to journalArticlepeer-review

122 Scopus citations


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(ε-caprolactone-co-lactide)-poly(ethylene glycol)-poly(ε- 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°C), whereas it formed a sol at pH 8.0 and 37°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.

Original languageEnglish
Pages (from-to)923-933
Number of pages11
JournalTissue Engineering - Part A
Issue number4
StatePublished - 1 Apr 2009


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