1 research outputs found
Injectable Shear-Thinning CaSO<sub>4</sub>/FGF-18-Incorporated Chitin–PLGA Hydrogel Enhances Bone Regeneration in Mice Cranial Bone Defect Model
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–polyÂ(lactide-<i>co</i>-glycolide) (PLGA)
composite hydrogel by regeneration chemistry and then incorporated
CaSO<sub>4</sub> and FGF-18 for this purpose. Rheologically, a 7-fold
increase in the elastic modulus was observed in the CaSO<sub>4</sub>-incorporated chitin–PLGA hydrogels as compared to the chitin–PLGA
hydrogel. Shear-thinning Herschel–Bulkley fluid nature was
observed for both hydrogels. Chitin–PLGA/CaSO<sub>4</sub> 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/CaSO<sub>4</sub> 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/CaSO<sub>4</sub> showed early and almost complete bone healing in comparison
with chitin–PLGA/CaSO<sub>4</sub>, chitin–PLGA/FGF-18,
chitin–PLGA, and sham control systems, as confirmed by hematoxylin
and eosin and osteoid tetrachrome stainings. This shows that the CaSO<sub>4</sub> and FGF-18-incorporated hydrogel is a potential candidate
for craniofacial bone defect regeneration