Efficient
delivery of bone morphogenetic protein-2 (BMP-2) with
desirable bioactivity is still a great challenge in the field of bone
regeneration. In this study, a silk fibroin/chitosan scaffold incorporated
with BMP-2-loaded mesoporous hydroxyapatite nanoparticles (mHANPs)
was prepared (SCH-L). BMP-2 was preloaded onto mHANPs with a high
surface area before mixing with a silk fibroin/chitosan composite.
Bare (without BMP-2) silk fibroin/chitosan/mHANP (SCH) scaffolds and
SCH scaffolds with directly absorbed BMP-2 (SCH-D) were investigated
in parallel for comparison. In vitro release kinetics indicated that
BMP-2 released from the SCH-L scaffold showed a significantly lower
initial burst release, followed by a more sustained release over time
than the SCH-D scaffold. In vitro cell viability, osteogenic differentiation
of bone marrow mesenchymal stem cells (BMSCs), and the in vivo osteogenic
effect of scaffolds in a rat calvarial defect were evaluated. The
results showed that compared with bare SCH and SCH-D scaffolds, the
SCH-L scaffold significantly promoted the osteogenic differentiation
of BMSCs in vitro and induced more pronounced bone formation in vivo.
Further studies demonstrated that the mHANP-mediated satisfactory
conformational change and sustained release benefited the protection
of the released BMP-2 bioactivity, as confirmed by alkaline phosphatase
(ALP) activity and a mineralization deposition assay. More importantly,
the interaction of BMP-2/mHANPs enhanced the binding ability of BMP-2
to cellular receptors, thereby maintaining its biological activity
in osteogenic differentiation and osteoinductivity well, which contributed
to the markedly promoted in vitro and in vivo osteogenic efficacy
of the SCH-L scaffold. Taken together, these results provide strong
evidence that mHANPs represent an attractive carrier for binding BMP-2
to scaffolds. The SCH-L scaffold shows promising potential for bone
tissue regeneration applications.
Treatments for infectious bone defects such as periodontitis require antibacterial and osteogenic differentiation capabilities. Nanotechnology has prompted the development of multifunctional material. In this research, we aim to synthesize a nanoparticle that can eliminate periodontal pathogenic microorganisms and simultaneously stimulate new bone tissue regeneration and mineralization. QAS-modified core-shell mesoporous silica containing Ag nanoparticles (Ag@QHMS) was successfully synthesized through the classic hydrothermal method and surface quaternary ammonium salt functionalization. The Ag@QHMS in vitro antibacterial activity was explored via coculture with Staphylococcus aureus, Escherichia coli, and Porphyromonas gingivalis biofilms. Bone mesenchymal stem cells (BMSCs) were selected for observing cytotoxicity, apoptosis, and osteogenic differentiation. Ag@QHMS showed a good sustained release profile of Ag+ and a QAS-grafted mesoporous structure. Compared with the single-contact antibacterial activity of QHMS, Ag@QHMS exhibited a more efficient and stable concentration-dependent antimicrobial efficacy; the minimum inhibitory concentration was within 100 μg/ml, which was below the BMSC biocompatibility concentration (200 μg/ml). Thus, apoptosis would not occur while promoting the increased expression of osteogenic-associated factors, such as runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteopontin (OPN), osteocalcin (OCN), bone sialoprotein (BSP), and collagen type 1 (COL-1). A safe concentration of particles can stimulate cell alkaline phosphatase and matrix calcium salt deposition. The dual antibacterial effect from the direct contact killing of QAS and the sustained release of Ag nanoparticles, along with the Ag-promoted osteogenic differentiation, had been verified and utilized in Ag@QHMS. This system demonstrates the potential for utilizing pluripotent biomaterials to treat complex lesions.
Background
Existing implant materials cannot meet the essential multifunctional requirements of repairing infected bone defects, such as antibacterial and osteogenesis abilities. A promising strategy to develop a versatile biomimicry composite of the natural bone structure may be accomplished by combining a multifunctional nanoparticle with an organic scaffold.
Methods
In this study, a quaternary ammonium silane-modified mesoporous silica containing nano silver (Ag@QHMS) was successfully synthesized and further combined with silk fibroin (SF) to fabricate the multifunctional nano-reinforced scaffold (SF-Ag@QHMS) using the freeze-drying method. Furthermore, the antibacterial and osteogenic effects of this composite were evaluated in vitro and in vivo.
Results
SF-Ag@QHMS inherited a three-dimensional porous structure (porosity rate: 91.90 ± 0.62%) and better mechanical characteristics (2.11 ± 0.06 kPa) than that of the SF scaffold (porosity rate: 91.62 ± 1.65%; mechanic strength: 2.02 ± 0.01 kPa). Simultaneously, the introduction of versatile nanoparticles has provided the composite with additional antibacterial ability against
Porphyromonas gingivalis
, which can be maintained for 15 days. Furthermore, the expression of osteogenic-associated factors was up-regulated due to the silver ions eluting from the composite scaffold. The in vivo micro-CT and histological results indicated that the new bone formation was not only localized around the border of the defect but also arose more in the center with the support of the composite.
Conclusion
The multifunctional silver-loaded mesoporous silica enhanced the mechanical strength of the composite while also ensuring greater and sustained antibacterial and osteogenic properties, allowing the SF-Ag@QHMS composite to be used to repair infected bone defects.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.