Background
Exosomes derived from bone marrow mesenchymal stem cells (BMSC-exos) have been shown triggering osteogenic differentiation and mineralization of MSCs, but exosomes administered via bolus injections are rapidly sequestered and cleared. Therefore, we considered the implant as a new organ of patient’s body and expected to find a method to treat implant with BMSC-exos in vivo directly.
Methods
A fusion peptide (PEP), as a drug delivery system (DDS) which contained a titanium-binding peptide (TBP) possessing the ability to selectively bind to the titanium surface and another peptide CP05 being able to capture exosomes expertly, is constructed to modify the titanium surface.
Results
Both in vitro and in vivo experiments prove PEP retains the ability to bind titanium and exosome simultaneously, and the DDS gain the ability to target exosomes to titanium implants surface following enhancing osseointegration post-implantation. Moreover, the DDS constructed by exosomes of diverse origins shows the similar combination rate and efficiency of therapy.
Conclusion
This drug delivery system demonstrates the concept that EXO-PEP system can offer an accurate and efficient therapy for treating implants with long-term effect.
Restoring bone homeostasis is the key to the treatment of osteoporosis. How to increase osteogenic ability or inhibit osteoclast activity has always been a topic of great concern. In recent years, short peptides with biological activity have received great attention in bone repair. However, the application of short peptides is still limited due to the lack of a stable and targeted delivery system. We designed poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles modified by alendronate (AL) to transport osteogenic peptides (OGP) (AL‐PLGA@P NPs). Benefiting from the high affinity of AL for hydroxyapatite, AL‐PLGA@P NPs have the ability to target bone. In this delivery system, OGP that promotes osteogenesis synergizes with AL, which inhibits osteoclasts, to regulate bone homeostasis, which gives them more advantages in the treatment of osteoporosis. Our data showed that nanoparticles could selectively deliver peptides to the bone surface without systemic toxicity. Moreover, nanoparticles could upregulate osteogenesis‐related factors (ALP, Runx‐2, BMP2) and downregulate osteoclast‐related factors (TRAP, CTSK) in vitro. With AL‐PLGA@P NPs, bone microarchitecture and bone mass were improved in ovariectomized osteoporosis rats. Therefore, this study proposes a novel osteoporosis‐based drug system that effectively improves bone density.This article is protected by copyright. All rights reserved
Background
Exosomes derived from bone marrow mesenchymal stem cells (BMSC-exos) have been shown triggering osteogenic differentiation and mineralization of MSCs,but exosomes administered via bolus injections are rapidly sequestered and cleared. Therefore, we considered the implant as a new organ of patient's body and expected to find a method to treat implant with BMSC-exos in vivo directly.
Methods
A fusion peptide (PEP), as a drug delivery system (DDS) which contained a titanium-binding peptide (TBP) possessing the ability to selectively bind to the titanium surface and another peptide CP05 being able to capture exosomes expertly, is constructed to modify the titanium surface.
Results
Both in vitro and in vivo experiments prove PEP retains the ability to bind titanium and exosome simultaneously, and the DDS gain the ability to target exosomes to titanium implants surface following enhancing osseointegration post-implantation. Moreover, the DDS constructed by exosomes of diverse origins shows the similar combination rate and efficiency of therapy.
Conclusion
This drug delivery system demonstrates the concept that EXO-PEP system can offer an accurate and efficient therapy for treating implants with long-term effect.
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