Solution combustion synthesis (SCS) of theranostic ions doped biphasic calcium phosphates; kinetic of ions release in simulated body fluid (SBF) and reactive oxygen species (ROS) generation.

Theranostic ions offer suitable platforms for cancer theranostics; here, the effect of doping various amounts of theranostic ions (i.e., Sr2+, Fe2+, and Ti4+ ions) on the physicochemical properties and biological activities of calcium phosphates (CaPs) were investigated. The solution combustion synthesis (SCS) was conducted at different amounts of ions (i.e., = 0.1, 0.25, 0.5 mol). Desirable physicochemical properties were obtained in doped samples with 0.1 mol of ions. The particle size of the Sr, Fe, and Ti-doped samples was decreased from 68 to 39, 24, and 29 nm, respectively. The surface charge of the mentioned samples was changed from -20 to -24, -28, and -25 mV, respectively. Besides, the specific surface area of the mentioned samples was significantly increased from 38 to 79, 65, and 106 m2/g, respectively. It was found that bioactivity of doped CaPs improved ~95%, which relied on the high adsorption and desorption rate of Ca2+ ions in the simulated body fluid (SBF). The in vitro cell-based results demonstrate the potent effect of CaPs and theranostic ions doped CaPs on the reactive oxygen species (ROS) generation. In the presence of CaPs, the intracellular ROS generation is increased by about 60%. Besides, the intracellular ROS generation is improved in Sr2+, Fe2+, and Ti4+ ions doped CaPs by about 66, 64, and 68%. As a result of the high generation of ROS, the bone nodule formation of cell treated CaPs and theranostic ions doped CaPs is improved 25%-37%. Finally, it can be concluded that the use of the SCS approaches for doping of theranostic ions causes well-physicochemical properties and high biological activities.

Silicon-doped calcium phosphates; the critical effect of synthesis routes on the biological performance.

In this study, the effect of using different types of fuel and various amounts of Si4+ ions on the biological properties of silicon-doped calcium phosphates (CaPs), which were synthesized using solution combustion method were investigated. X-ray diffraction (XRD) patterns showed that hydroxyapatite/beta-tricalcium phosphate (HA/ßTCP) was crystallized in all synthesized samples. The synthesized sample using glycine as fuel, which doped with 0.1 mol Si4+ ions exhibited the most desirable properties. Consecutively, the zeta potential and specific surface area were enhanced from -20 to -27 mV and 38 to 146 m2/g, respectively, by increasing the amount of Si4+ ions from 0 to 0.1 mol. The bioactivity of the samples immersed in simulated body fluid (SBF) was innovatively determined by the joint analyses of the tensiometer, inductively coupled plasma (ICP), field emission scanning electron microscopy (FESEM), and XRD data. These findings plus theoretical calculations demonstrate, for the first time, that the Si4+ doping could improve the bioactivity of the powders up to ~155%. The results of in vitro cell-based experiments, including cell viability, alizarin red staining, and cell attachment, confirmed the positive effects of Si-doped powders in the biological systems. Furthermore, Si-doped powders were able to improve the migration ability of mammalian cells in vitro; they could be considered good candidates in angiogenesis-based therapeutic strategies.

Accelerated wound healing in a diabetic rat model using decellularized dermal matrix and human umbilical cord perivascular cells.

There is an unmet clinical need for novel wound healing strategies to treat full thickness skin defects, especially in diabetic patients. We hypothesized that a scaffold could perform dual roles of a biomechanical support and a favorable biochemical environment for stem cells. Human umbilical cord perivascular cells (HUCPVCs) have been recently reported as a type of mesenchymal stem cell that can accelerate early wound healing in skin defects. However, there are only a limited number of studies that have incorporated these cells into natural scaffolds for dermal tissue engineering. The aim of the present study was to promote angiogenesis and accelerate wound healing by using HUCPVCs and decellularized dermal matrix (DDM) in a rat model of diabetic wounds. The DDM scaffolds were prepared from harvested human skin samples and histological, ultrastructural, molecular and mechanical assessments were carried out. In comparison with the control (without any treatment) and DDM alone group, full thickness excisional wounds treated with HUCPVCs-loaded DDM scaffolds demonstrated an accelerated wound closure rate, faster re-epithelization, more granulation tissue formation and decreased collagen deposition. Furthermore, immunofluorescence analysis showed that the VEGFR-2 expression and vascular density in the HUCPVCs-loaded DDM scaffold treated group were also significantly higher than the other groups at 7days post implantation. Since the rates of angiogenesis, re-epithelization and formation of granulation tissue are directly correlated with full thickness wound healing in patients, the proposed HUCPVCs-loaded DDM scaffolds may fulfil a role neglected by current treatment strategies. This pre-clinical proof-of-concept study warrants further clinical evaluation. STATEMENT OF SIGNIFICANCE: The aim of the present study was to design a novel tissue-engineered system to promote angiogenesis, re-epithelization and granulation of skin tissue using human umbilical cord perivascular stem cells and decellularized dermal matrix natural scaffolds in rat diabetic wound models. The authors of this research article have been working on stem cells and tissue engineering scaffolds for years. According to our knowledge, there is a lack of an efficient system for the treatment of skin defects using tissue engineering strategy. Since the rates of angiogenesis, re-epithelization and granulation tissue are directly correlated with full thickness wound healing, the proposed HUCPVCs-loaded DDM scaffolds perfectly fills the niche neglected by current treatment strategies. This pre-clinical study demonstrates the proof-of-concept that necessitates clinical evaluations.