Abstract
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 language | English (US) |
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Pages (from-to) | 1743-1752 |
Number of pages | 10 |
Journal | Journal of Biomedical Materials Research - Part A |
Volume | 106 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2018 |
Funding
This research was supported by the NIH Chemistry of Life Processes Pre-doctoral Training Grant under Award #5T32GM105538-03. Special thank you to Drs. Chad Haney and Alex Waters of the Center for Advanced Molecular Imaging (CAMI) at Northwestern University for assisting with radiographic imaging and assessment. Additional Supporting Information may be found in the online version of this article. No benefit of any kind will be received either directly or indirectly by the author(s) Correspondence to: [Guillermo A. Ameer, DSc, Biomedical Engineering Department, Department of Surgery, and Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois, USA]; e-mail: [email protected] Contract grant sponsor: National Institute of General Medical Sciences; contract grant number: 5T32GM15538-03
Keywords
- bioengineering
- bone µCT
- fracture healing
- matrix mineralization
- stem cells
ASJC Scopus subject areas
- Ceramics and Composites
- Biomaterials
- Biomedical Engineering
- Metals and Alloys