Quercetin-solid lipid nanoparticle-embedded hyaluronic acid functionalized hydrogel for immunomodulation to promote bone reconstruction

Bone defects are a persistent challenge in clinical practice. Although repair therapies based on tissue-engineered materials, which are known to have a crucial role in defective bone regeneration, have gathered increased attention, the current treatments for massive bone defects have several limitations. In the present study, based on the immunomodulatory inflammatory microenvironment properties of quercetin, we encapsulated quercetin-solid lipid nanoparticles (SLNs) in a hydrogel. Temperature-responsive poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide) modifications were coupled to the main chain of hyaluronic acid hydrogel, constructing a novel, injectable bone immunomodulatory hydrogel scaffold. Extensive in vitro and in vivo data showed that this bone immunomodulatory scaffold forms an anti-inflammatory microenvironment by decreasing M1 polarization, while elevating the M2 polarization. Synergistic effects on angiogenesis and anti-osteoclastic differentiation were observed. These findings further proved that administering quercetin SLNs encapsulated in a hydrogel can aid bone defect reconstruction in rats, providing new insights for large-scale bone defect repair.