Melatonin-loaded mesoporous zinc- and gallium-doped hydroxyapatite nanoparticles to control infection and bone repair.

Effective treatment of infected bone defects resulting from multi-drug resistant bacteria (MDR) has emerged as a significant clinical challenge, highlighting the pressing demand for potent antibacterial bone graft substitutes. Mesoporous nanoparticles have been introduced as a promising class of biomaterials offering significant properties for treating bone infections. Herein, we synthesize antibacterial mesoporous hydroxyapatite substituted with zinc and gallium (Zn-Ga:mHA) nanoparticles using a facile sol-gel method. The resulting mesoporous nanoparticles are applied for the controlled release of melatonin (Mel). Zn-Ga:mHA nanoparticles with an average particle size of 36 ± 3 nm and pore size of 10.6 ± 0.4 nm reveal a Mel loading efficiency of 58 ± 1%. Results show that 50% of Mel is released within 20 h and its long-term release is recorded up to 50 h. The Zn-Ga:mHA nanoparticles exhibit highly effective antibacterial performance as reflected by a 19 ± 1% and 8 ± 2% viability reduction in Escherichia coli and Staphylococcus bacteria, respectively. Noticeably, Mel-loaded Zn-Ga:mHA nanoparticles are also cytocompatible and stimulate in vitro osteogenic differentiation of human mesenchymal stem cells (hMSCs) without any osteoinductive factor. In vivo studies in a rabbit skull also show significant regeneration of bone during 14 days. In summary, Mel-loaded Zn-Ga:mHA nanoparticles provide great potential as an antibacterial and osteogenic component in bone substitutes like hydrogels, scaffolds, and coatings.

Engineering Wet-Resistant and Osteogenic Nanocomposite Adhesive to Control Bleeding and Infection after Median Sternotomy.

Median sternotomy surgery stands as one of the prevailing strategies in cardiac surgery. In this study, the cutting-edge bone adhesive is designed, inspired by the impressive adhesive properties found in mussels and sandcastle worms. This work has created an osteogenic nanocomposite coacervate adhesive by integrating a cellulose-polyphosphodopamide interpenetrating network, quaternized chitosan, and zinc, gallium-doped hydroxyapatite nanoparticles. This adhesive is characterized by robust catechol-metal coordination which effectively adheres to both hard and soft tissues with a maximum adhesive strength of 900 ± 38 kPa on the sheep sternum bone, surpassing that of commercial bone adhesives. The release of zinc and gallium cations from nanocomposite adhesives and quaternized chitosan matrix imparts remarkable antibacterial properties and promotes rapid blood coagulation, in vitro and ex vivo. It is also proved that this nanocomposite adhesive exhibits significant in vitro bioactivity, stable degradability, biocompatibility, and osteogenic ability. Furthermore, the capacity of nanocomposite coacervate to adhere to bone tissue and support osteogenesis contributes to the successful healing of a sternum bone defect in a rabbit model in vivo. In summary, these nanocomposite coacervate adhesives with promising characteristics are expected to provide solutions to clinical issues faced during median sternotomy surgery.

Synergic role of zinc and gallium doping in hydroxyapatite nanoparticles to improve osteogenesis and antibacterial activity.

Recently, postoperative bone infections have been one of the most crucial challenges for surgeons. This study aims to synergistically promote antibacterial and osteoconductive properties of hydroxyapatite (HAp) nanoparticles through binary doping of Zn2+ and Ga3+ ions (Zn-Ga:HAp). Zn-Ga:HAp nanopowders with spherical morphology and homogeneous size are synthesized using a simple sol-gel method. Substitution of both zinc and gallium in the structure of HAp results in a gradual decrease in the lattice parameters as doping level increases, limits the growth of HAp particles and reduces its crystallinity. Noticeably, the crystallinity of HAp (85%) reduces to less than 73% (for XZn = 0.1), 78% (for XGa = 0.4) and 75% (for XZn = 0.1 and XGa = 0.4). Ion doping also significantly modulate the release of bioactive ions (Ca2+, PO43-, Zn2+, Ga3+) from the Zn-Ga:HAp depended on the overall amount of Ga and Zn in the HAp, which could mediate the biological responses. Incorporating both Zn2+ and Ga3+ ions in HAp structure could significantly improve the antibacterial activity of HAp nanopowders against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) with a concentration-dependent effect. Noticeably, Zn-Ga:HAp (XZn = 0.1 and XGa = 0.4) powder shows the antibacterial activity of more than 68% and 84% against E. coli and S. aureus, respectively, at the concentration of 500 µg/ml, thereby showing excellent antibacterial properties. In addition, Zn-Ga:HAp nanopowders not only do not exhibit any cytotoxicity towards hMSCs, but also show significantly superior osteogenic properties. For instance, Zn-Ga:HAp (XZn = 0.1 and XGa = 0.4) nanopowders significantly enhance the alkaline phosphatase activity (approximately 2-fold) and mineralization (approximately 3-fold) of hMSCs after 14 days of culture, compared to pure HAp. Overall, Zn-Ga:HAp (XZn = 0.1 and XGa = 0.4) with desired osteogenesis and antibacterial activity compared to pure HAp, Zn:HAp and Ga:HAp shows promising opportunities for the implant-associated infections and the efficient healing of bone defects.

Strong and bioactive bioinspired biomaterials, next generation of bone adhesives.

The bone adhesive is a clinical requirement for complicated bone fractures always articulated by surgeons. Applying glue is a quick and easy way to fix broken bones. Adhesives, unlike conventional fixation methods such as wires and sutures, improve healing conditions and reduce postoperative pain by creating a complete connection at the fractured joint. Despite many efforts in the field of bone adhesives, the creation of a successful adhesive with robust adhesion and appropriate bioactivity for the treatment of bone fractures is still in its infancy. Because of the resemblance of the body's humid environment to the underwater environment, in the latest decades, researchers have pursued inspiration from nature to develop strong bioactive adhesives for bone tissue. The aim of this review article is to discuss the recent state of the art in bone adhesives with a specific focus on biomimetic adhesives, their action mechanisms, and upcoming perspective. Firstly, the adhesive biomaterials with specific affinity to bone tissue are introduced and their rational design is studied. Consequently, various types of synthetic and natural bioadhesives for bone tissue are comprehensively overviewed. Then, bioinspired-adhesives are described, highlighting relevant structures and examples of biomimetic adhesives mainly made of DOPA and the complex coacervates inspired by proteins secreted in mussel and sandcastle worms, respectively. Finally, this article overviews the challenges of the current bioadhesives and the future research for the improvement of the properties of biomimetic adhesives for use as bone adhesives.