Well-Ordered Mesoporous Silica and Bioactive Glasses: Promise for Improved Hemostasis

Immediate control of uncontrolled bleeding and infection are essential for saving lives in both combat and civilian arenas. Inorganic well-ordered mesoporous silica and bioactive glasses have recently shown great promise for accelerating hemostasis and infection control. However, to date, there has been no comprehensive report assessing their specific mechanism of action in accelerating the hemostasis process and exerting an antibacterial effect. After providing a brief overview of the hemostasis process, this review presents a critical overview of the recently developed inorganic mesoporous silica and bioactive glass-based materials proposed for hemostatic clinical applications and specifically investigates their unique characteristics that render them applicable for hemostatic applications and preventing infections. This article also identifies promising new research directions that should be undertaken to ascertain the effectiveness of these materials for hemostatic applications

Inorganic Hemostats: The State-Of-The-Art and Recent Advances

Hemorrhage is the most common cause of death both in hospitals and on the battlefield. The need for an effective hemostatic agent remains, since all injuries are not amenable to tourniquet use. There are many topical hemostatic agents and dressings available to control severe bleeding. This article reviews the most commonly used inorganic hemostats, subcategorized as zeolite and clay-based hemostats. Their hemostatic functions as well as their structural properties that are believed to induce hemostasis are discussed. The most important findings from in vitro and in vivo experiments are also covered

Hydrothermal Synthesis and Characterisation of Bioactive Glass-Ceramic Nanorods

In this study fabrication of rod-like bioactive glass-ceramics (BGCs) using hydrothermal treatment based on a sol-gel precursor is reported for the first time. BGCs with composition 58 wt% SiO2, 33 wt% CaO and 9 wt% P2O5 were synthesized in different thermal conditions (200 and 220 °C) and characterised with regard to morphology, chemical composition and crystallinity. The bioactivity of the materials was assessed by immersion in simulated body fluid for up to 7 days. The results revealed that as the reaction temperature increased from 200 to 220 °C, the diameter of rods was reduced from microscale to nanoscale and the crystallinity was enhanced. It was also found that the BGC nanorods have higher surface area and consequently enhanced bioactivity than BGC microrods. This technique provides a facile method for rapid production of BGC nanorods at relatively low temperature which may have the potential to be used as bioactive composite reinforcement or for bone grafting applications

Gallium-Containing Mesoporous Bioactive Glass with Potent Hemostatic Activity and Antibacterial Efficacy

Haemorrhage remains the leading cause of potentially survivable death in both military and civilian populations. Although a large variety of hemostatic agents have been developed, many of them have an inadequate capacity to induce hemostasis and are not effective in killing bacteria. In recent years, mesoporous bioactive glasses (MBGs) were found to be effective in inducing hemostasis. However, the materials may not be considered as ideal hemostats since they do not offer antimicrobial activity. The gallium ion (Ga+3) not only exhibits antibacterial properties but also accelerates the blood coagulation cascade. The aim of this study was to develop MBGs containing various concentrations of Ga2O3 (1, 2 & 3 mol%) via the evaporation-induced self-assembly (EISA) process and investigate whether the addition of Ga3+ would induce both hemostatic and antibacterial effects. The results indicated that the incorporation of lower Ga2O3 content (1 mol%) into the MBG system improved structural properties including the specific surface area, mesopore size and pore volume as well as the release of silicon and calcium ions. The bioactive glass was found to stimulate blood coagulation, platelet adhesion and thrombus generation and exerted an antibacterial effect against both Escherichia coli and Staphylococcus aureus. Likewise, Ga-doped MBGs showed excellent cytocompatibility even after 3 days, with the 1% Ga2O3-containing MBG attaining the best biocompatibility that render them safe hemostatic agents for stopping bleeding. This study demonstrated that the lowest Ga2O3-substituted MBG can be a potent candidate for controlling haemorrhage and wound infection

Fabrication and Characterization of Poly(Octanediol Citrate)/gallium-Containing Bioglass Microcomposite Scaffolds

Bone can be affected by osteosarcomae requiring surgical excision of the tumor as part of the treatment regime. Complete removal of cancerous cells is difficult and conventionally requires the removal of a margin of safety around the tumor to offer improved patient prognosis. This work considers a novel series of composite scaffolds based on poly (octanediol citrate) (POC) impregnated with gallium-based bioglass microparticles for possible incorporation into bone following tumor removal. The objective of this research was to fabricate and characterize these scaffolds and subsequently report on their mechanical and biological properties. The porous micro composite scaffolds with various concentrations of bio glass (10, 20, 30 wt%) incorporated were fabricated using a salt leaching technique. The scaffolds exhibited compression modulus in the range of 0.3–7 MPa. The addition of bio glass increased the mechanical properties even though porosity increased. Furthermore, increasing the concentration of bio glass had a significant influence on glass transition temperature from 2.5 °C for the pure polymer to around 25 °C for 30 % bio glass-containing composite. The ion release study revealed that composites containing 10 % bio glass had the highest ion release ratio after 28 days of soaking in phosphate buffered saline. The interaction of bio glass phase with POC led to the formation of additional ionic crosslinks aside from covalent crosslinks which further resulted in increased stiffness and decreased weight loss. The osteoblast cells were well attached and growth on composites and collagen synthesis increased particularly with the 10 % bio glass concentration

Potency and Cytotoxicity of a Novel Gallium-Containing Mesoporous Bioactive Glass/Chitosan Composite Scaffold as Hemostatic Agents

Chitosan-based hemostats are promising candidates for immediate hemorrhage control. However, they have some disadvantages and require further improvement to achieve the desired hemostatic efficiency. Here, a series of 1% Ga2O3-containing mesoporous bioactive glass-chitosan composite scaffolds (Ga-MBG/CHT) were constructed by the lyophilization process and the effect of various concentrations of Ga-MBG (10, 30, and 50 wt %) on the hemostatic function of the CHT scaffold was assessed as compared to that of Celox Rapid gauze (CXR), a current commercially available chitosan-coated hemostatic gauze. The prepared scaffolds exhibited \u3e79% porosity and showed increased water uptake compared to that in CXR. The results of coagulation studies showed that pure CHT and composite scaffolds exhibited increased hemostatic performance with respect to CXR. Furthermore, the composite scaffold with the highest Ga-MBG content (50 wt %) had increased capability to enhancing thrombus generation, blood clotting, and platelet adhesion and aggregation than that of the scaffold made of pure CHT. The antibacterial efficacy and biocompatibility of the prepared scaffolds were also assessed by a time-killing assay and an Alamar Blue assay, respectively. Our results show that the antibacterial effect of 50% Ga-MBG/CHT was more pronounced than that of CHT and CXR. The cell viability results also demonstrated that Ga-MBG/CHT composite scaffolds had good biocompatibility, which facilitates the spreading and proliferation of human dermal fibroblast cells even with 50 wt % Ga-MBG loading. These results suggest that Ga-MBG/CHT scaffolds could be a promising hemostatic candidate for improving hemostasis in critical situations

Synthesis of new supramolecular elastomers from sunflower oil and palm acid oil

New supramolecular elastomers were synthesized using vegetable oil materials namely palm acid oil (PAO) and sunflower oil (SFO). The oils were first epoxidized by using formic acid and hydrogen peroxide. The epoxidized oils and adipic acid (AA) were then reacted to make polyacids, mainly triacid. Molar ratio of 1:10 for epoxidized oils and AA led to the formation of higher reactive groups of synthesized polyacid without gelation. Finally, diethylenetriamine (DETA) was added to polyacid to yield oligomers and a polycondensation with urea performed to achieve the desired elastomers. The synthesized materials were characterized by using Fourier Transform Infrared (FTIR) and Nuclear Magnetic Resonance (NMR) in order to determine structure and type of bonding. The spectra reveals that the synthesized oligomers are contained amide groups that correctly formed from reaction of amine groups of DETA and acid functionality of polyacids. Moreover, the resulted structures show the formation of multiple hydrogen-bonding in the elastomers

A poly (octanediol citrate)/gallium-containing bioglass composite for bone tissue regeneration / Ehsan Zeimaran

Bone can be affected by osteosarcomae requiring surgical excision of the tumor as part of a treatment regime. Complete removal of cancerous cells is difficult and conventionally requires the removal of a margin of safety around the tumor to offer improved patient prognosis. Gallium has been shown to be clinically effective, both against bone resorption and for the treatment of cancer-related hypercalcemia. This work considers a novel series of composite scaffolds based on poly (octanediol citrate) (POC) impregnated with a gallium-containing bioactive glass (0.48SiO2-0.12CaO- 0.32ZnO-0.08Ga2O3, molar fraction) microparticles for possible incorporation into bone following tumor removal. The objective of this research was to fabricate and characterize these scaffolds and subsequently report on their mechanical, thermal, structural and biological properties. The porous microcomposite scaffolds, with various concentrations of bioactive glass (10, 20, 30 wt%) incorporated, were fabricated using a salt leaching technique. The scaffolds exhibited compression moduli in the range of 0.3-7 MPa. The addition of bioactive glass increased the mechanical properties even though porosity increased. Furthermore, increasing the concentration of bioactive glass had a significant influence on glass transition temperature from 2.5 °C for the pure polymer to approximately 25 °C for 30 % bioactive glass-containing composite. The ion release study revealed that composites containing 30 % bioactive glass had the highest ion release ratio after 28 days of soaking in phosphate buffered saline (PBS). The interaction of the bioactive glass phase with POC led to the formation of additional ionic crosslinks, aside from the covalent crosslinks, which further resulted in increased stiffness and decreased weight loss. The antibacterial activity of these scaffolds was investigated against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria in vitro. The ability of the scaffolds to release ions and the subsequent ingress of these ions into hard tissue was evaluated using a bovine bone model. Scaffolds containing bioactive glass exhibited antibacterial activity which increased with higher bioactive glass loads; viable cells decreased to about 20 % for the composite scaffold containing 30 % bioactive glass. The Ga3+ release rate increased as a function of time and Zn2+ was shown to incorporate into the surrounding bone. The effect of composite scaffolds on growth and osteogenic differentiation of human osteoblast-like cells and human bone marrow-derived mesenchymal stem cells (hBMSCs) was investigated. The osteoblastlike cells were well attached and growth on composites and collagen synthesis increased particularly with the 10 % bioactive glass concentration. All the scaffolds were able to support the growth of hBMSCs and guide their osteogenic differentiation without osteogenic media stimulation. The expression of bone-associated genes (collagen I, osteonectin and osteocalcin, bone morphogenetic protein 2, runt-related transcription factor 2) was significantly increased by a culture time for of up to 2 weeks, particularly for the composite scaffolds loaded with 10 % bioactive glass. The composite scaffolds significantly stimulated alkaline phosphatase (ALP) activity compared to the pure POC scaffolds. Cellular mineralization of the secreted extracellular matrix illustrated a higher calcium level on the composites than pure POC, and increased with culture time. These results suggest that composite scaffolds of POC and a bioactive glass doped with therapeutic elements provides favourable conditions for osteogenic differentiation of hBMSCs and can potentially be used to induce bone healing and regeneration

Synthesis and characterization of supramolecular elastomers from polyacids composed of vegetable oils

Supramolecular elastomers were synthesized using vegetable oil materials namely palm acid oil (PAO) and sunflower oil (SFO). The oils were first epoxidized using formic acid and hydrogen peroxide. The epoxidized oils and adipic acid were then reacted to make polyacids, mainly triacid. Finally, diethylenetriamine (DETA) was added to polyacid to yield fatty amide and a polycondensation with urea performed to achieve the desired elastomers. The synthesized materials were characterized by using Fourier Transform Infrared (FTIR), Nuclear Magnetic Resonance (NMR) and Thermogravimetric Analyzer (TGA) in order to determine structure, type of bonding and thermal stability. The spectrums revealed that the synthesized fatty amides are contained amide groups that correctly formed from reaction of amine groups of DETA and acid functionality of polyacids. Moreover, the resulted structures showed the formation of multiple hydrogen-bonding in the elastomers. TGA thermograms clearly indicated good thermal stability of the elastomers to 500 °C

Polymeric Hydrogel Systems as Emerging Biomaterial Platforms to Enable Hemostasis and Wound Healing

Broad interest in developing new hemostatic technologies arises from unmet needs in mitigating uncontrolled hemorrhage in emergency, surgical, and battlefield settings. Although a variety of hemostats, sealants, and adhesives are available, development of ideal hemostatic compositions that offer a range of remarkable properties including capability to effectively and immediately manage bleeding, excellent mechanical properties, biocompatibility, biodegradability, antibacterial effect, and strong tissue adhesion properties, under wet and dynamic conditions, still remains a challenge. Benefiting from tunable mechanical properties, high porosity, biocompatibility, injectability and ease of handling, polymeric hydrogels with outstanding hemostatic properties have been receiving increasing attention over the past several years. In this review, after shedding light on hemostasis and wound healing processes, the most recent progresses in hydrogel systems engineered from natural and synthetic polymers for hemostatic applications are discussed based on a comprehensive literature review. Most studies described used in vivo models with accessible and compressible wounds to assess the hemostatic performance of hydrogels. The challenges that need to be tackled to accelerate the translation of these novel hemostatic hydrogel systems to clinical practice are emphasized and future directions for research in the field are presented