Median sternotomy surgery is one of the most common access methods in heart and chest surgery. Sternotomy wound healing may be associated with sternal wound infection, osteomyelitis, or mediastinitis. Although there is currently no suitable bone adhesive to control bleeding from the edges of the sternum after sternotomy, inspired by marine organisms in water such as mussel and sandcastle worms, the aim of this research is to develop biomimetic adhesive based on chitosan and hydroxyapatite nanoparticles substituted with zinc and gallium (Zn-Ga:HAp) containing melatonin drug. Hydroxyapatite nanoparticles substituted with zinc and gallium with spherical morphology and homogeneous size were synthesized using a simple sol-gel method and a surfactant called CTAB was used as a template. Ion substitution significantly modulated the release of bioactive ions Ca2+, PO43-, Zn2+ and Ga3+. Also, the simultaneous release of Zn2+ and Ga3+ ions in the structure of hydroxyapatite nanoparticles substituted with zinc and gallium (XZn=0.1 and XGa=0.4), the antibacterial activity is more than 68±6% and 84±8% in against Staphylococcus aureus and Escherichia coli, respectively, at a concentration of 500 µg/ml. Next, mesoporous nanoparticles with a pore size of 10.65 nm were used to improve the melatonin drug absorption capacity and stabilize its release. The results showed that the loading efficiency of melatonin increased from 27±0.03% in dense nanoparticles to 58.9±0.65% in mesoporous nanoparticles. Mesoporous nanoparticles released 50% of the drug during the first 20 hours and its long-term release was recorded up to 50 hours. The results of the quantitative expression of osteogenesis genes including alkaline phosphatase, osteocalcin, collagen I and RUNX2 resulting from the differentiation of mesenchymal cells in nanoporous hydroxyapatite substituted with zinc and gallium containing melatonin on days 3, 7 and 14 had a significant increase compared to other samples. In order to investigate the ossification capability of mesoporous nanoparticles of hydroxyapatite substituted with zinc and gallium (XZn=0.1 and XGa=0.4), an animal test was performed by creating four bone defects in the cranium of a rabbit; The highest result in bone regeneration in bone defects including optimized nanoparticles containing melatonin drug was reported. In the following, coacervate adhesive was synthesized based on chitosan and including the interpenetrating polymer network of cellulose and polyphosphodopamide copolymer with 〖"EDTA/FeCl" 〗_"3" complex as a crosslinker. Then coacervate adhesive was composited with mesoporous hydroxyapatite nanoparticles substituted with zinc and gallium (XZn=0.1 and XGa=0.4). Phase and chemical characterization of the desired adhesive was done by X-ray diffraction test, infrared spectroscopy with Fourier transform and inductively coupled plasma atomic emission spectrometer, and all components of the adhesive were identified. In order to eva‎luate the adhesiveness of the synthesized adhesive, the adhesive strength was tested by the ASTM F2255-05 adhesive strength test. In the results of the adhesive strength on the glass substrate, by adding 2% by weight of nanoparticles to the C2 adhesive, the shear strength was 900.4±38 kPa. The shear strength of this adhesive was 19.647±9 kPa and 27.8±2 kPa on sheep sternum bone and cow skin substrate, respectively, which showed the high ability of this adhesive to adhere to different substrates. Also, in order to eva‎luate the adhesive strength in wet environment, C2 adhesive showed shear strength of 144±1.12 kPa on bone substrate and 18±1.2 kPa for skin substrate. Also, to eva‎luate the adhesion strength in wet environment, C2 adhesive showed shear strength of 144±1.12 kPa on bone substrate and 18±1.2 kPa for skin substrate in wet conditions.

مهشيد خرازيهاي اصفهاني , حسين احمدي تفتي

روح الله مهدي نواز اقدم , محمدرضا باغبان اسلامي نژاد

محمد ديناري , ژاله ورشوساز , علي حسين رضايان قيه