A thermoresponsive, citrate-based macromolecule for bone regenerative engineering

Simona Morochnik, Yunxiao Zhu, Chongwen Duan, Michelle Cai, Russell R. Reid, Tong Chuan He, Jason Koh, Igal Szleifer, Guillermo A. Ameer

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


There is a need in orthopaedic and craniomaxillofacial surgeries for materials that are easy to handle and apply to a surgical site, can fill and fully conform to the bone defect, and can promote the formation of new bone tissue. Thermoresponsive polymers that undergo liquid to gel transition at physiological temperature can potentially be used to meet these handling and shape-conforming requirements. However, there are no reports on their capacity to induce in vivo bone formation. The objective of this research was to investigate whether the functionalization of the thermoresponsive, antioxidant macromolecule poly(poly-ethyleneglycol citrate-co-N-isopropylacrylamide) (PPCN), with strontium, phosphate, and/or the cyclic RGD peptide would render it a hydrogel with osteoinductive properties. We show that all formulations of functionalized PPCN retain thermoresponsive properties and can induce osteodifferentiation of human mesenchymal stem cells without the need for exogenous osteogenic supplements. PPCN-Sr was the most osteoinductive formulation in vitro and produced robust localized mineralization and osteogenesis in subcutaneous and intramuscular tissue in a mouse model. Strontium was not detected in any of the major organs. Our results support the use of functionalized PPCN as a valuable tool for the recruitment, survival, and differentiation of cells critical to the development of new bone and the induction of bone formation in vivo.

Original languageEnglish
Pages (from-to)1743-1752
Number of pages10
JournalJournal of Biomedical Materials Research - Part A
Issue number6
StatePublished - Jun 2018
Externally publishedYes


  • bioengineering
  • bone µCT
  • fracture healing
  • matrix mineralization
  • stem cells


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