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.
Recombinant vitronectin-grafted hydrogels were developed by adjusting surface charge of the hydrogels with grafting of poly-l-lysine for optimal culture of human embryonic stem cells (hESCs) under xeno- and feeder-free culture conditions, with elasticity regulated by crosslinking time (10-30 kPa), in contrast to conventional recombinant vitronectin coating dishes, which have a fixed stiff surface (3 GPa). hESCs proliferated on the hydrogels for over 10 passages and differentiated into the cells derived from three germ layers indicating the maintenance of pluripotency. hESCs on the hydrogels differentiated into cardiomyocytes under xeno-free culture conditions with much higher efficiency (80% of cTnT+ cells) than those on conventional recombinant vitronectin or Matrigel-coating dishes just only after 12 days of induction. It is important to have an optimal design of cell culture biomaterials where biological cues (recombinant vitronectin) and physical cues (optimal elasticity) are combined for high differentiation of hESCs into specific cell lineages, such as cardiomyocytes, under xeno-free and feeder-free culture conditions.
Current xeno-free and chemically defined methods for the differentiation of hPSCs (human pluripotent stem cells) into cardiomyocytes are not efficient and are sometimes not reproducible. Therefore, it is necessary to develop reliable and efficient methods for the differentiation of hPSCs into cardiomyocytes for future use in cardiovascular research related to drug discovery, cardiotoxicity screening, and disease modeling. We evaluated two representative differentiation methods that were reported previously, and we further developed original, more efficient methods for the differentiation of hPSCs into cardiomyocytes under xeno-free, chemically defined conditions. The developed protocol successively differentiated hPSCs into cardiomyocytes, approximately 90-97% of which expressed the cardiac marker cTnT, with beating speeds and sarcomere lengths that were similar to those of a healthy adult human heart. The optimal cell culture biomaterials for the cardiac differentiation of hPSCs were also evaluated using extracellular matrix-mimetic material-coated dishes. Synthemax II-coated and Laminin-521-coated dishes were found to be the most effective and efficient biomaterials for the cardiac differentiation of hPSCs according to the observation of hPSC-derived cardiomyocytes with high survival ratios, high beating colony numbers, a similar beating frequency to that of a healthy adult human heart, high purity levels (high cTnT expression) and longer sarcomere lengths similar to those of a healthy adult human heart.
Polyhydroxyalkanoate (PHA) is a microbial polymer that has been at the forefront of many attempts at tissue engineering. However, the surface of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P(3HB-co-4HB)) is hydrophobic with few recognition sites for cell attachment. Various concentrations of fish-scale collagen peptides (FSCPs) were incorporated into P(3HB-co-4HB) copolymer by aminolysis. Later, FSCPs were introduced onto the aminolyzed P(3HB-co-4HB) scaffolds. Introduction of the FSCP groups was verified using Fourier transform infrared spectroscopy and the ninhydrin method. The effect of the incorporation of FSCPs on hydrophilicity was investigated using the water contact angle. As the concentration of FSCPs increased, the water contact angle decreased. In vitro study demonstrated that P(3HB-co-4HB)/FSCP scaffolds provided better cell attachment and growth of L929 mouse fibroblast cells and better cell proliferation. In vivo study showed that P(3HB-co-4HB)/1.5 wt% FSCPs had a significant effect on wound contractions, with the highest percentage of wound closure (61%) in 7 d.
Mesoporous bioactive glass containing 1% Ga2O3 (1%Ga-MBG) is attractive for hemorrhage control because of its surface chemistry which can promote blood-clotting. The present study compares this proprietary inorganic coagulation accelerator with two commercial hemostats, CeloxTM (CX) and QuikClot Advanced Clotting Sponge PlusTM (ACS+). The results indicate that the number of adherent platelets were higher on the 1%Ga-MBG and CX surfaces than ACS+ whereas a greater contact activation was seen on 1%Ga-MBG and ACS+ surfaces than CX. 1%Ga-MBG not only resulted in larger platelet aggregates and more extensive platelet pseudopodia compared to CX and ACS+ but also significantly accelerated the intrinsic pathways of the clotting cascade. In vitro thrombin generation assays also showed that CX and ACS+ induced low levels of thrombin formation while 1%Ga-MBG had significantly higher values. 1%Ga-MBG formed a larger red blood cell aggregate than both CX and ACS+. Direct exposure of 1%Ga-MBG to fibroblast cells increased cell viability after 3 days relative to CX and ACS+, inferring excellent cytocompatibility. The results of this study promote 1%Ga-MBG as a promising hemostat compared to the commercially available products as it possesses essential factors required for coagulation activation.
Advances in scaffold design and fabrication technology have brought the tissue engineering field stepping into a new era. Conventional techniques used to develop scaffolds inherit limitations, such as lack of control over the pore morphology and architecture as well as reproducibility. Rapid prototyping (RP) technology, a layer-by-layer additive approach offers a unique opportunity to build complex 3D architectures overcoming those limitations that could ultimately be tailored to cater for patient-specific applications. Using RP methods, researchers have been able to customize scaffolds to mimic the biomechanical properties (in terms of structural integrity, strength, and microenvironment) of the organ or tissue to be repaired/replaced quite closely. This article provides intensive description on various extrusion based scaffold fabrication techniques and review their potential utility for TE applications. The extrusion-based technique extrudes the molten polymer as a thin filament through a nozzle onto a platform layer-by-layer and thus building 3D scaffold. The technique allows full control over pore architecture and dimension in the x- and y- planes. However, the pore height in z-direction is predetermined by the extruding nozzle diameter rather than the technique itself. This review attempts to assess the current state and future prospects of this technology.
Global issues such as environmental problems and food security are currently of concern to all of us. Circular bioeconomy is a promising approach towards resolving these global issues. The production of bioenergy and biomaterials can sustain the energy-environment nexus as well as substitute the devoid of petroleum as the production feedstock, thereby contributing to a cleaner and low carbon environment. In addition, assimilation of waste into bioprocesses for the production of useful products and metabolites lead towards a sustainable circular bioeconomy. This review aims to highlight the waste biorefinery as a sustainable bio-based circular economy, and, therefore, promoting a greener environment. Several case studies on the bioprocesses utilising waste for biopolymers and bio-lipids production as well as bioprocesses incorporated with wastewater treatment are well discussed. The strategy of waste biorefinery integrated with circular bioeconomy in the perspectives of unravelling the global issues can help to tackle carbon management and greenhouse gas emissions. A waste biorefinery-circular bioeconomy strategy represents a low carbon economy by reducing greenhouse gases footprint, and holds great prospects for a sustainable and greener world.
Three-dimensionally printed constructs are static and do not recapitulate the dynamic nature of tissues. Four-dimensional (4D) bioprinting has emerged to include conformational changes in printed structures in a predetermined fashion using stimuli-responsive biomaterials and/or cells. The ability to make such dynamic constructs would enable an individual to fabricate tissue structures that can undergo morphological changes. Furthermore, other fields (bioactuation, biorobotics, and biosensing) will benefit from developments in 4D bioprinting. Here, the authors discuss stimuli-responsive biomaterials as potential bioinks for 4D bioprinting. Natural cell forces can also be incorporated into 4D bioprinted structures. The authors introduce mathematical modeling to predict the transition and final state of 4D printed constructs. Different potential applications of 4D bioprinting are also described. Finally, the authors highlight future perspectives for this emerging technology in biomedicine.
Dentistry is highly energy and resource intensive with significant environmental impact. Factors inherent in the profession such as enormous electricity demands of electronic dental equipment, voluminous water requirements, environmental effects of biomaterials (before, during and after clinical use), the use of radiation and the generation of hazardous waste involving mercury, lead etc have contributed towards this. With rising temperatures across the world due to global warming, efforts are being made worldwide to mitigate the effects of environmental damage by resorting to sustainability concepts and green solutions in a myriad of ways. In such a scenario, a professional obligation and social responsibility of dentists makes it imperative to transform the practice of dentistry from a hazardous to a sustainable one, by adopting environmental-friendly measures or 'green dentistry'. The NHS in the UK has been proactive in implementing sustainability in healthcare by setting targets, developing guidance papers, initiating steering groups to develop measures and implementing actions through its Sustainable Development Unit (SDU). Such sustainable frameworks, specific to dentistry, are not yet available and even the scientific literature is devoid of studies in this field although anecdotal narratives abound. Hence this paper attempts to present a comprehensive evaluation of the existing healthcare sustainability principles, for their parallel application in the field of dentistry and lays out a blueprint for integrating the two main underlying principles of sustainability - resource use efficiency and eliminating or minimising pollution - in the day-to-day practice. The article also highlights the importance of social values, community care, engaging stakeholders, economic benefits, developing policy and providing leadership in converting the concept of green dentistry into a practised reality.
The main aim of this study was to investigate the effect of different coating materials (i.e. Na-alginate and chitosan) on the viability and release behavior of Bifidobacterium pseudocatenulatum G4 in the simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). This study reports the viability of encapsulated B. pseudocatenulatum G4 coated using different alginate (2-4 g/100mL) and chitosan (0.2-0.8 g/100mL) concentrations. The results indicated that the highest concentration of alginate (4.4142 g/100mL) along with 0.5578 g/100mL chitosan resulted in the highest viability of B. pseudocatenulatum G4. The release behavior of the encapsulated probiotics in SGF (pH 1.5) in 2h followed by 4h in SIF (pH 7.4) was also assessed. The resistance rate of alginate-chitosan capsule in SGF was higher than SIF. The alginate-chitosan encapsulated cells had also more resistance than alginate capsules. The current study revealed that alginate encapsulated B. Pseudocatenulatum G4 exhibited longer survival than its free cells (control).
Bionanocomposite films based on regenerated cellulose (RC) and incorporated with zeolite at different concentrations were fabricated by dissolving cellulose in 1-ethyl-3-methylimidazolium chloride (EMIMCl) ionic liquid using a simple green method. The interactions between the zeolite and the cellulose matrix were confirmed by Fourier transform infrared spectra. Mechanical properties of the nanocomposite films significantly improved as compared with the pure regenerated cellulose film, without the loss of extensibility. Zeolite incorporation enhanced the thermal stability and char yield of the nanocomposites. The scanning electron microscopy and transmission electron microscopy showed that zeolite was uniformly dispersed in the regenerated cellulose matrix. In vitro cytotoxicity test demonstrated that both RC and RC/zeolite nanocomposite films are cytocompatible. These results indicate that the prepared nanocomposites have potential applications in biodegradable packaging, membranes and biomedical areas.
Chitin was successfully grafted with polystyrene by free radical mechanism using ammonium persulfate (APS) initiator. The reaction was carried out in aqueous medium. The effect of pH, chitin:monomer weight ratio, APS, reaction time and reaction temperature were investigated. The results showed that the optimum conditions for grafting of polystyrene were found as follows: pH 7, chitin:monomer weight ratio of 1:3, 0.4 g of APS, reaction temperature of 60 °C and reaction time 2 h. The graft copolymer was characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis (TGA) and differential scanning electron microscopy (DSC). Gel permeation chromatography (GPC) analysis carried out on the hydrolyzed graft copolymer showed that the Mn and Mw were 6.3395×10(4) g/mol and 1.69283×10(5) g/mol, respectively, with polydispersity index of 2.7.
Acetone soluble oil palm empty fruit bunch cellulose acetate (OPEFB-CA) of DS 2.52 has been successfully synthesized in a one-step heterogeneous acetylation of OPEFB cellulose without necessitating the hydrolysis stage. This has only been made possible by the mathematical modeling of the acetylation process by manipulating the variables of reaction time and acetic anhydride/cellulose ratio (RR). The obtained model was verified by experimental data with an error of less than 2.5%. NMR analysis showed that the distribution of the acetyl moiety among the three OH groups of cellulose indicates a preference at the C6 position, followed by C3 and C2. XRD revealed that OPEFB-CA is highly amorphous with a degree of crystallinity estimated to be ca. 6.41% as determined from DSC. The OPEFB-CA films exhibited good mechanical properties being their tensile strength and Young's modulus higher than those of the commercial CA.
Blends of poly (1, 8-octanediol citrate) (POC) and chitosan (CS) were prepared through solution casting technique. Films with different component fractions (POC/CS: 100/0, 90/10, 80/20, 70/30, 60/40, and 0/100) were successfully prepared and characterized for their mechanical, thermal, structural and morphological properties as well as biocompatibility. The incorporation of CS to POC significantly increased tensile strength and elastic modulus and presented limited influences on pH variation which is important to the biocompatibility of biomaterial implants. The assessment of surface topography indicated that blending could enhance and control the surface roughness of the pure films. POC/CS blends well-supported human dermal fibroblast cells attachment and proliferation, and thus can be used for a range of tissue engineering applications.
Chitosan, as a biodegradable and biocompatible polymer, is characterized by anti-microbial and anti-cancer properties. It lately has received a widespread interest for use as the pulmonary particulate backbone materials of drug carrier for the treatment of infectious disease and cancer. The success of chitosan as pulmonary particulate drug carrier is a critical interplay of their mucoadhesive, permeation enhancement and site/cell-specific attributes. In the case of nanocarriers, various microencapsulation and micro-nano blending systems have been devised to equip them with an appropriate aerodynamic character to enable efficient pulmonary aerosolization and inhalation. The late COVID-19 infection is met with acute respiratory distress syndrome and cancer. Chitosan and its derivatives are found useful in combating HCoV and cancer as a function of their molecular weight, substituent type and its degree of substitution. The interest in chitosan is expected to rise in the next decade from the perspectives of drug delivery in combination with its therapeutic performance.
Carboxymethyl starch (CMS) was produced from sago starch via carboxymethylation. The CMS with different degree of substitution (DS) ranges from 0.4 to 0.8 were mixed with polyethylene glycol (PEG) of different molecular weight and distilled water and the hydrogel was cured by electron beam irradiation with doses ranging from 25 to 35 kGy. The results revealed that CMS-PEG hydrogels with DS 0.4 give the optimum gel content when radiated at 30 kGy and with PEG 600. Thermogravimetric analysis (TGA) revealed that there are two phases exist in CMS with DS 0.4 in contrast to the three steps decomposition occurs in DS 0.6 and 0.8. It shows that the CMS with DS 0.4 is more thermally stable. Surface morphology revealed crosslinking among the blends when subjected into the radiation dose. The study shows both radiation and PEG addition improved most of the properties of CMS irrespective of the DS value.
Lactoferrin (Lf) nanoparticles have been developed as a carrier of drugs and gene. Two main methods, desolvation technique and emulsification method, for preparation of protein nanoparticles have been reported so far, but most of the previous reports of Lf nanoparticles preparation are limited to emulsification method. In this study, we investigated the optimal conditions by desolvation technique for the preparation of glutaraldehyde-crosslinked bovine Lf (bLf) nanoparticles within the size range of 100-200 nm, and evaluated their properties as a carrier for oral and intravenous drug delivery. The experimental results of dynamic light scattering and Transmission Electron Microscope suggested that glutaraldehyde-crosslinked bLf nanoparticles with 150 nm in size could be produced by addition of 2-propanol as the desolvating solvent into the bLf solution adjusted to pH 6, followed by crosslinking with glutaraldehyde. These cross-linked bLf nanoparticles were found to be compatible to blood components and resistant against rapid degradation by pepsin. Thus, cross-linked bLf nanoparticles prepared by desolvation technique can be applied as a drug carrier for intravenous administration and oral delivery.
Bovine pericardium has widely been used for grafts in cardiac surgery and seems to have suitable properties for use as a dural graft. We report our experience of using locally processed bovine pericardium for dural grafts in 22 patients undergoing cranial operations.
The kinetic and thermodynamic adsorption and adsorption isotherms of Pb(II) and Cu(II) ions onto H(2)SO(4) modified chitosan were studied in a batch adsorption system. The experimental results were fitted using Freundlich, Langmuir and Dubinin-Radushkevich isotherms; the Langmuir isotherm showed the best conformity to the equilibrium data. The pseudo-first order, pseudo-second order and intraparticle diffusion kinetic models were employed to analyze the kinetic data. The adsorption behavior of Pb(II) and Cu(II) was best described by the pseudo-second order model. Thermodynamic parameters such as free energy change (DeltaG degrees ), enthalpy change (DeltaH degrees ) and entropy change (DeltaS degrees ) were determined; the adsorption process was found to be both spontaneous and exothermic. No physical damage to the adsorbents was observed after three cycles of adsorption/desorption using EDTA and HCl as eluents. The mechanistic pathway of the Pb(II) and Cu(II) uptake was examined by means of Fourier transform infrared (FTIR) and Energy dispersive X-ray (EDX) spectroscopy. The equilibrium parameter (R(L)) indicated that chitosan-H(2)SO(4) was favorable for Pb(II) and Cu(II) adsorption.
Casein nanomicelles, a major fraction of milk protein, are emerging as a novel drug delivery system owing to their various structural and functional properties. Casein is further divided into α-, β- and κ-casein, and to date various models have been proposed to describe casein structure, but still no definite structure presenting a detailed assembly of the casein micelle has been found. Thus far, the submicellar model and Horne and Holt model are the most accepted models. This article presents a detailed review of casein micelles and their fractions, and the physicochemical properties that account for their numerous applications in nutraceutics, pharmaceutics and cosmetics. Due to their nanosize and self-assembling nature, casein nanomicelles are considered as excellent delivery carriers to provide better bioavailability and stability of various compounds such as vitamins, oils, polyphenols, fattyacids and minerals. Their amphiphilic nature also provides a great opportunity to deliver hydrophobic bioactives in various drug delivery systems such as nanoparticles, nanomicelles, nanogels and nanoemulsions to improve drug binding and targeting.