Osteoimmunity‐Regulating Biomimetically Hierarchical Scaffold for Augmented Bone Regeneration

Abstract

Engineering a proper immune response following biomaterial implantation is essential to bone tissue regeneration. Herein, a biomimetically hierarchical scaffold composed of deferoxamine@poly(ε‐caprolactone) nanoparticles (DFO@PCL NPs), manganese carbonyl (MnCO) nanosheets, gelatin methacryloyl hydrogel, and a polylactide/hydroxyapatite (HA) matrix is fabricated to augment bone repair by facilitating the balance of the immune system and bone metabolism. First, a 3D printed stiff scaffold with a well‐organized gradient structure mimics the cortical and cancellous bone tissues; meanwhile, an inside infusion of a soft hydrogel further endows the scaffold with characteristics of the extracellular matrix. A Fenton‐like reaction between MnCO and endogenous hydrogen peroxide generated at the implant‐tissue site triggers continuous release of carbon monoxide and Mn2+, thus significantly lessening inflammatory response by upregulating the M2 phenotype of macrophages, which also secretes vascular endothelial growth factor to induce vascular formation. Through activating the hypoxia‐inducible factor‐1α pathway, Mn2+ and DFO@PCL NP further promote angiogenesis. Moreover, DFO inhibits osteoclast differentiation and synergistically collaborates with the osteoinductive activity of HA. Based on amounts of data in vitro and in vivo, strong immunomodulatory, intensive angiogenic, weak osteoclastogenic, and superior osteogenic abilities of such an osteoimmunity‐regulating scaffold present a profound effect on improving bone regeneration, which puts forward a worthy base and positive enlightenment for large‐scale bone defect repair.

Nanotopographical cues for regulation of macrophages and osteoclasts: emerging opportunities for osseointegration

“…To address the drawbacks and accelerate clinical translation, various of nanotopographies with diverse parameters and subsequent high-throughput screening are in demand, which relies on the breakthrough of the fabrication methods bottleneck. It is well-known that 3D printing can precisely control biomaterial macro-structure[ 178 ]. In combination with nanofibers electrospinning, the interior micro-architecture can also be tailored [ 179 ].…”

Biodegradable ZnxNi1−xS hollow nanospheres for NIR-driven photothermal antibacterial therapy

“…Finally, the routine blood parameters were acquired and the major organs were stained with H&E after treatment. 54,55…”

“…Finally, the routine blood parameters were acquired and the major organs were stained with H&E after treatment. 54,55 Biosafety evaluation and biodegradable behavior of the ZNSP nanostructures…”

Application of single and cooperative different delivery systems for the treatment of intervertebral disc degeneration

“…Zhou et al ( Zhou et al, 2020 ) presented a simple method that combined poly (vinyl alcohol) (PVA) hydrogels with PCL and reflected a new type of microsphere with a PVA core and PCL shell. Unfortunately, due to its slow decomposition in vivo , PCL is mainly used as a scaffold material to repair AF or osteonecrosis, and its use as a microsphere-based delivery system in IDD has been rarely reported ( Shamsah et al, 2019 ; Zhang et al, 2022a ).…”