Osseointegration of implants depends
on several intertwined factors:
osteogenesis, angiogenesis, and immunomodulation. Lately, novel reinforcements
allowing faster bonding with osseous tissue have been explored intensively.
In this study, we hypothesized the use of boron as a major multifunctional
ion to confer versatility to calcium-deficient hydroxyapatite (cHA)
synthesized by a wet precipitation/microwave reflux method. By synthesis
of boron-doped calcium-deficient hydroxyapatite (BcHA), we expected
to obtain an osteoimmunomodulatory and regenerative nanoreinforcement.
BcHA was found to possess a pure HA phase, a greater surface area
(66.41 m
2
/g,
p
= 0.028), and cumulative
concentrations of Ca (207.87 ± 6.90 mg/mL,
p
< 0.001) and B (112.70 ± 11.79 mg/mL,
p
< 0.001) released in comparison to cHA. Osteogenic potential
of BcHA was analyzed using human fetal osteoblasts. BcHA resulted
in a drastic increase in the ALP activity (1.11 ± 0.11 mmol/gDNA·min,
p
< 0.001), biomineralization rate, and osteogenic gene
expressions compared to cHA. BcHA angiogenic potential was investigated
using human umbilical cord vein endothelial cells. Significantly,
the highest VEGF-A release (1111.14 ± 87.82 in 4 h,
p
= 0.009) and angiogenic gene expressions were obtained for BcHA-treated
samples. These samples were also observed to induce a more prominent
and highly branched tube network. Finally, inflammatory and inflammasome
responses toward BcHA were elucidated using human monocyte-derived
macrophages differentiated from THP-1s. BcHA exhibited lower CAS-1
release (50.18 ± 5.52 μg/g
DNA
μg/gDNA)
and higher IL-10 release (126.97 ± 15.05 μg/g
DNA
) than cHA. In addition, BcHA treatment led to increased expression
of regenerative genes such as VEGF-A, RANKL, and BMP-2. In vitro results
demonstrated that BcHA has tremendous osteogenic, angiogenic, and
immunomodulatory potential to be employed as a “versatile-in-all-trades”
modality in various bone tissue engineering applications.