Multifunctional bone repair platform: Cytokines scavenging and sequential drug release for osteoporotic bone defects
Year: 2025
Type: article
Abstract: The repair of osteoporotic bone defect (OBD) continues to be challenged by the persistent inflammatory imbalance and impaired osteogenesis. Inspired by the immunomodulatory role of macrophages, we developed a multifunctional bone repair platform consisting of macrophage membrane-liposome hybrid nanovesicles (MM-Lipo) embedded in the GelMA hydrogel. The MM-Lipo nanovesicles, which present membrane-anchored cytokine receptors, effectively scavenged excess RANKL, TNF-α, IL-6 at the defect sites, thereby regulating the local microenvironment. The aqueous core of the nanovesicles allowed for the encapsulation of the hydrophilic teriparatide (PTH 1–34). The GelMA hydrogel served as a sustained-release reservoir, facilitating the sequential delivery of both nanovesicles and drug to promote osteogenic differentiation. In vitro , MM-Lipo efficiently depleted cytokines, inhibited RANKL-induced osteoclastogenesis, and reversed the inhibitory effects TNF-α on osteoblast function. The teriparatide-loaded formulation (MM-Lipo@PTH) further upregulated the expression of osteogenic markers (OSX, OCN) and promoted mineralized matrix deposition. In the mouse OBD model, a single implantation of the GelMA/MM-Lipo@PTH hydrogel rebalanced osteoclast and osteoblast activity, accelerated bone regeneration, and supported well-organized collagen architecture. This synergistic strategy integrates the cytokines-scavenging capability of biomimetic membrane with the controlled, sequential release properties of hydrogel, offering a promising therapeutic platform for inflammation-associated metabolic bone disorders. Abbreviations: ALP, Alkaline phosphatase; ALT, Alanine Aminotransferase; AST, Aspartate aminotransferase; BCA, Bicinchoninic acid; BCIP/NBT, 5-bromo-4-chloro-3-indolyl phosphate/nitro blue tetrazolium; BMSC, bone mesenchymal stem cells; BUN, Blood urea nitrogen; CCK-8, Cell counting kit-8; CREA, Creatinine; DAPI, 4′,6-diamidino-2-phenylindole; Dil, 1,1′-Dioctadecyl-3,3,3′,3′-Tetramethylindocar bocyanine Perchlorate; DiO, 3,3′-Dioctadecyloxacar bocyanine perchlorate; ECL, Enhanced chemiluminescence; EDTA, Ethylenediaminetetraacetic acid; ELISA, Enzyme-linked immunosorbent assay; FBS, Fetal bovine serum; FRET, Förster resonance energy transfer; GelMA, Gelatin methacryloyl; H&E, hematoxylin and eosin; IL-6, Interleukin-6; LAP, Lithium phenyl-2,4,6-trimethylbenzoylphosphinate; α-MEM, α-minimum essential medium; OCN, Osteocalcin; OSX, Osterix; PBS, Phosphate buffered saline; PVDF, Polyvinylidene fluoride; RANKL, Receptor activator of nuclear factor-κ B ligand; SDS-PAGE, Sodium dodecyl sulfate–polyacrylamide gel electrophoresis; TBST, Tris-buffered saline with tween-20; TNF-α, Tumor necrosis factor α; TRAP, Tartrate-resistant acid phosphatase; TRITC, Tetramethylrhodamine isothiocyanate.
Source: Materials & Design
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,650
Award: G643519018
OpenAlex ID: W4416379702