Biomaterial–immune
system interactions play an important
role in postimplantation osseointegration to retain the functionality
of healthy and intact bones. Therefore, appropriate osteoimmunomodulation
of implants has been considered and validated as an efficient strategy
to alleviate inflammation and enhance new bone formation. Here, we
fabricated a nanostructured PCL/PVP (polycaprolactone/polyvinylpyrrolidone)
electrospinning scaffold for cell adhesion, tissue ingrowth, and bone
defect padding. In addition, telmisartan, an angiotensin 2 receptor
blocker with distinct immune bioactivity, was doped into PCL-/PVP-electrospun
scaffolds at different proportions [1% (TPP-1), 5% (TPP-5), and 10%
(TPP-10)] to investigate its immunomodulatory effects and osteoinductivity/conductivity.
Telmisartan-loaded scaffolds displayed in vitro anti-inflammatory
bioactivity on lipopolysaccharide-induced M1 macrophages by polarizing
them to an M2-like phenotype and exhibited pro-osteogenic properties
on bone marrow-derived mesenchymal stem cells (BMSCs). Histological
analysis and micro-CT results of a rat skull defect model also showed
that the telmisartan-loaded scaffolds induced a higher M2/M1 ratio,
less inflammatory infiltration, and better bone regenerative patterns.
Furthermore, activation of the BMP2 (bone morphogenetic protein-2)-Smad
signaling pathway was found to be dominant in telmisartan-loaded scaffold-mediated
macrophage–BMSC interactions. These findings indicate that
telmisartan incorporation with PCL/PVP nanofibrous scaffolds is a
potential therapeutic strategy for promoting bone healing by modulating
M1 macrophages to a more M2 phenotype at early stages of postimplantation.