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Injectable Shear Thinning CaSO4/FGF-18 incorporated Chitin-PLGA Hydrogels Enhances Bone Regeneration in Mice Cranial Bone Defect Model

Publication Type : Journal Article

Thematic Areas : Nanosciences and Molecular Medicine

Publisher : ACS Applied Materials & Interfaces,

Source : ACS Applied Materials & Interfaces, Volume 9, p.42639–42652 (2017)

Campus : Kochi

School : Center for Nanosciences

Center : Amrita Center for Nanosciences and Molecular Medicine Move, Nanosciences

Department : Nanosciences, Nanosciences and Molecular Medicine

Verified : Yes

Year : 2017

Abstract : For craniofacial bone regeneration, shear-thinning injectable hydrogels are favored over conventional scaffolds because of their improved defect margin adaptability, easier handling, and ability to be injected manually into deeper tissues. The most accepted method, after autografting, is the use of recombinant human bone morphogenetic protein-2 (BMP-2); however, complications such as interindividual variations, edema, and poor cost-efficiency in supraphysiological doses have been reported. The endogenous synthesis of BMP-2 is desirable, and a molecule which induces this is fibroblast growth factor-18 (FGF-18) because it can upregulate the BMP-2 expression by supressing noggin. We developed a chitin–poly(lactide-co-glycolide) (PLGA) composite hydrogel by regeneration chemistry and then incorporated CaSO4 and FGF-18 for this purpose. Rheologically, a 7-fold increase in the elastic modulus was observed in the CaSO4-incorporated chitin–PLGA hydrogels as compared to the chitin–PLGA hydrogel. Shear-thinning Herschel–Bulkley fluid nature was observed for both hydrogels. Chitin–PLGA/CaSO4 gel showed sustained release of FGF-18. In vitro osteogenic differentiation showed an enhanced alkaline phosphatase (ALP) expression in the FGF-18-containing chitin–PLGA/CaSO4 gel when compared to cells alone. Further, it was confirmed by studying the expression of osteogenic genes [RUNX2, ALP, BMP-2, osteocalcin (OCN), and osteopontin (OPN)], immunofluorescence staining of BMP-2, OCN, and OPN, and alizarin red S staining. Incorporation of FGF-18 in the hydrogel increased the endothelial cell migration. Further, the regeneration potential of the prepared hydrogels was tested in vivo, and longitudinal live animal μ-CT was performed. FGF-18-loaded chitin–PLGA/CaSO4 showed early and almost complete bone healing in comparison with chitin–PLGA/CaSO4, chitin–PLGA/FGF-18, chitin–PLGA, and sham control systems, as confirmed by hematoxylin and eosin and osteoid tetrachrome stainings. This shows that the CaSO4 and FGF-18-incorporated hydrogel is a potential candidate for craniofacial bone defect regeneration.

Cite this Research Publication : Amirthalingam Sivashanmugam, Pornkawee, C., Deepthi, S., Arunkumar, R., Nair, S. V., Iseki, S., and Dr. Jayakumar Rangasamy, “Injectable Shear Thinning CaSO4/FGF-18 incorporated Chitin-PLGA Hydrogels Enhances Bone Regeneration in Mice Cranial Bone Defect Model”, ACS Applied Materials & Interfaces, vol. 9, pp. 42639–42652, 2017.

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