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

Abstract

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) (PCLA) modifications were coupled to the main chain of hyaluronic acid (HA) 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.

Magnetic Graphene Oxide Nanocomposites Boosts Craniomaxillofacial Bone Regeneration by Modulating circAars/miR-128-3p/SMAD5 Signaling Axis

“…[31][32][33][34] However, as a kind of nanoparticles, MGO is not easily aggregated in the area of bone defects, so other scaffold materials or static magnetic fields need to be combined to repair large-scale bone defects. 7,35,36 Therefore, whether MGO has potential in BTE for craniomaxillofacial bone repair is worth further exploration. Because of the multidirectional differentiation potential, BMSCs are considered as candidates in bone regeneration.…”

Nanotechnological Research for Regenerative Medicine: The Role of Hyaluronic Acid

“…The hydrogel was nontoxic for osteoblast cells except for the highest incorporation of titanium dioxide NPs. Zhou et al [73] exploited the immunomodulatory potential of quercetin by formulating a new composite hydrogel using quercetin-loaded solid lipid NPs homogeneously packed into an HA hydrogel combined with a temperature-responsive poly(e-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(e-caprolactone-co-lactide) polymer. This scaffold was able to create an immune microenvironment responsible for promoting the recruitment and differentiation of bone marrow MSCs, stimulating angiogenesis and regulating osteoclast homeostasis.…”

Recent Progress in Hyaluronic-Acid-Based Hydrogels for Bone Tissue Engineering

“…Very recently, an HA hydrogel combined with a temperature-responsive synthetic polymer and quercetin-loaded solid lipid nanoparticle was developed for bone tissue engineering (Figure 10) [94]. This HA-based hydrogel showed an anti-inflammatory effect resulting from a decrease in M1 polarization and an increase in M2 polarization.…”