posted on 2018-09-05, 00:00authored bySivashanmugam Amirthalingam, Ashvin Ramesh, Seunghun S. Lee, Nathaniel S. Hwang, Rangasamy Jayakumar
The
in situ forming injectable hydrogels are appealing for irregular
bone defects because of the ease of administration and the addition
of ceramics, molecules, and proteins into the hydrogel. We have developed
in situ shape-forming hydrogel using oxidized alginate and gelatin
as the hydrogel matrix. Whitlockite bioceramic nanoparticles (WH NPs)
were incorporated, as they provide enhanced osteogenic stimulation
compared to hydroxyapatite via providing higher local ion concentration.
The drug simvastatin was also incorporated into the hydrogel system,
as it increases the expression of BMP-2 thereby provide environment
for bone regeneration. The presence of both WH nanoparticles and simvastatin
would enhance bone regeneration potential. The whitlockite nanoparticles
(80 ± 8 nm) were synthesized by precipitation method and were
characterized. The nanocomposite hydrogel system was characterized
by SEM, FTIR and rheologically. The gelation time of the in situ nanocomposite
hydrogel was determined by rheological analysis as 28 s, whereas hydrogel
alone showed 132 s. Addition of WH NPs not only shortened the gelation
time but also increased the gel strength. The in vitro release of
simvastatin from the nanocomposite hydrogel showed a release over
a period of 28 days. The alkaline phosphatase (ALP) level also showed
a significant increase. RUNX2 and BMP2 expressions showed that nanocomposite
hydrogel enhanced the osteogenic differentiation. In vivo bone regeneration
studies in mice cranial defect studies showed nanocomposite hydrogel
was effective in regenerating the bone compared to controls. Thus,
the simvastatin-incorporated oxidized alginate-gelatin/WH NPs hydrogel
system has the potential to be used as a repairing and regenerative
system in cranial bone defects.