TL;DR: This protocol includes methods to extract silk from B. mori cocoons to fabricate hydrogels, tubes, sponges, composites, fibers, microspheres and thin films, used directly as biomaterials for implants, as scaffolding in tissue engineering and in vitro disease models, as well as for drug delivery.
Abstract: Silk fibroin, derived from Bombyx mori cocoons, is a widely used and studied protein polymer for biomaterial applications. Silk fibroin has remarkable mechanical properties when formed into different materials, demonstrates biocompatibility, has controllable degradation rates from hours to years and can be chemically modified to alter surface properties or to immobilize growth factors. A variety of aqueous or organic solvent-processing methods can be used to generate silk biomaterials for a range of applications. In this protocol, we include methods to extract silk from B. mori cocoons to fabricate hydrogels, tubes, sponges, composites, fibers, microspheres and thin films. These materials can be used directly as biomaterials for implants, as scaffolding in tissue engineering and in vitro disease models, as well as for drug delivery.
TL;DR: In this article, the authors summarize synthesis strategies of water-soluble fluorescent metal nanoclusters and their optical properties, highlight recent advances in their application for ultrasensitive biological detection and fluorescent biological imaging, and finally discuss current challenges for their potential biomedical applications.
TL;DR: The general characteristics of the polymerization reaction and recent approaches that have been taken to improve composite restorative performance are reviewed.
Abstract: Composite dental restorations represent a unique class of biomaterials with severe restrictions on biocompatibility, curing behavior, esthetics, and ultimate material properties. These materials are presently limited by shrinkage and polymerization-induced shrinkage stress, limited toughness, the presence of unreacted monomer that remains following the polymerization, and several other factors. Fortunately, these materials have been the focus of a great deal of research in recent years with the goal of improving restoration performance by changing the initiation system, monomers, and fillers and their coupling agents, and by developing novel polymerization strategies. Here, we review the general characteristics of the polymerization reaction and recent approaches that have been taken to improve composite restorative performance.
TL;DR: The most recent research progresses on the synthesis, controlled drug release and delivery, pharmacokinetics and biocompatibility of MSNs are reviewed.
Abstract: The biomedical applications of mesoporous silica nanoparticles (MSNs) as efficient drug delivery carriers have attracted great attention in the last decade. The structure, morphology, size, and surface properties of MSNs have been found to be facilely tunable for the purposes of drug loading, controlled drug release and delivery, and multifuctionalization. Meanwhile, the biosafety and in vivo drug efficiency of MSN-based nano drug delivery systems (nano-DDSs), involving biocompatibility (including cytotoxicity, blood and tissue compatibility) and pharmacokinetics (including biodistribution, biodegradation, retention, excretion, blood circulation) are also drawing increasing attention because of their clinical application prospects. Herein, we review the most recent research progresses on the synthesis, controlled drug release and delivery, pharmacokinetics and biocompatibility of MSNs.
TL;DR: Results suggested that graphene oxide might be a promising material for biomedical applications, especially for targeted drug delivery to the lung, however, due to its high accumulation and long time retention, significant pathological changes were found at the dosage of 10 mg kg(-1) body weight.
TL;DR: The results reveal that graphene substrates exhibited excellent biocompatibility, as cell viability and morphology were not affected and neurites, one of the key structures for neural functions, are affected by graphene during the development until maturation in a mouse hippocampal culture model.
TL;DR: In vitro and in vivo imaging tests indicate that Eu(3+)/Gd (3+)-doped HAp nanorods have a potential in applications such as a multiple-model imaging agent for magnetic resonance (MR) imaging, photoluminescence imaging and computed tomography (CT) imaging.
TL;DR: The usage of nanoparticles, synthesized with Z. officinale extract, as vectors for the applications in drug delivery, gene delivery or as biosensors, where a direct contact with blood occurs is justified.
TL;DR: Three distinct outcomes were found for the presence of Sr: increased HA solubility; no significant effect on the degradation rate of CS; apparent inhibition of the otherwise rapid degradation of BS; and clear evidence that an optimum Sr dose exists.
TL;DR: This review provides an overview of silk biomaterials for drug delivery, especially those that can function as long-term depots and specific examples of implantable silk drug delivery systems and injectable systems from the 1990s and onwards are reviewed.
Abstract: Introduction: Given the benefits of polymer drug delivery implants over traditional periodic systemic administration, the development of biomaterial systems with the necessary properties (biocompatibility, degradation, stabilization, controllability) is paramount. Silk fibroin represents a promising, naturally derived polymer for local, controlled, sustained drug release from fully degrading implants and the polymer can be processed into a broad array of material formats. Areas covered: This review provides an overview of silk biomaterials for drug delivery, especially those that can function as long-term depots. Fundamentals of structure and assembly, processing options, control points and specific examples of implantable silk drug delivery systems (sponges, films) and injectable systems (microspheres, hydrogels) from the 1990s and onwards are reviewed. Expert opinion: Owing to its unique material properties, stabilization effects and tight controllability, silk fibroin is a promising biomaterial for imp...
TL;DR: The focus of this review paper is on processes that can be used to develop surface morphologies and chemical structures for the prevention of adhesion and proliferation of pathogenic bacteria on the surfaces of in-dwelling medical devices.
TL;DR: In vivo exploration suggests that although γ-Fe2O3 nanoparticles are rapidly cleared through the urine, they can lead to toxicity in the liver, kidneys and lungs, while the brain and heart remain unaffected.
Abstract: Nanotechnology is an exciting field of investigation for the development of new treatments for many human diseases However, it is necessary to assess the biocompatibility of nanoparticles in vitro and in vivo before considering clinical applications Our characterization of polyol-produced maghemite γ-Fe2O3 nanoparticles showed high structural quality The particles showed a homogeneous spherical size around 10 nm and could form aggregates depending on the dispersion conditions Such nanoparticles were efficiently taken up in vitro by human endothelial cells, which represent the first biological barrier to nanoparticles in vivo However, γ-Fe2O3 can cause cell death within 24 hours of exposure, most likely through oxidative stress Further in vivo exploration suggests that although γ-Fe2O3 nanoparticles are rapidly cleared through the urine, they can lead to toxicity in the liver, kidneys and lungs, while the brain and heart remain unaffected In conclusion, γ-Fe2O3 could exhibit harmful properties and therefore surface coating, cellular targeting, and local exposure should be considered before developing clinical applications
TL;DR: The potential of using plant proteins for tissue engineering and drug delivery has been explored as mentioned in this paper, mostly with zein, which can be made into fibers, films, hydrogels and micro-and nano-particles for medical applications.
TL;DR: The results indicated that collagen-chitosan-TPU blended nanofibrous scaffolds might be a potential candidate for vascular repair and nerve regeneration.
TL;DR: The study focuses on the synthesis of a novel polymeric scaffold having good porosity and mechanical characteristics synthesized by using natural polymers and their optimization for application in cartilage tissue engineering and suggests the potential of CAG cryogels as a good three-dimensional scaffold for cartilage tissues engineering.
Abstract: The study focuses on the synthesis of a novel polymeric scaffold having good porosity and mechanical characteristics synthesized by using natural polymers and their optimization for application in cartilage tissue engineering. The scaffolds were synthesized via cryogelation technology using an optimized ratio of the polymer solutions (chitosan, agarose and gelatin) and cross-linker followed by the incubation at sub-zero temperature (2128C). Microstructure examination of the chitosan – agarose – gelatine (CAG) cryogels was done using scanning electron microscopy (SEM) and fluorescent microscopy. Mechanical analysis, such as the unconfined compression test, demonstrated that cryogels with varying chitosan concentrations, i.e. 0.5 – 1% have a high compression modulus. In addition, fatigue tests revealed that scaffolds are suitable for bioreactor studies where gels are subjected to continuous cyclic strain. In order to confirm the stability, cryogels were subjected to high frequency (5 Hz) with 30 per cent compression of their original length up to 1 � 10 5 cycles, gels did not show any significant changes in their mass and dimensions during the experiment. These cryogels have exhibited degradation capacity under aseptic conditions. CAG cryogels showed good cell adhesion of primary goat chondrocytes examined by SEM. Cytotoxicity of the material was checked by MTT assay and results confirmed the biocompatibility of the material. In vivo biocompatibility of the scaffolds was checked by the implantation of the scaffolds in laboratory animals. These results suggest the potential of CAG cryogels as a good three-dimensional scaffold for cartilage tissue engineering.
TL;DR: The results showed that the photocurable polylactide (PLA) resin can be readily structured via direct laser write (DLW) with a femtosecond Ti:sapphire laser and submicrometer structures can be produced.
Abstract: This study reports on the production of high-resolution 3D structures of polylactide-based materials via multi-photon polymerization and explores their use as neural tissue engineering scaffolds. To achieve this, a liquid polylactide resin was synthesized in house and rendered photocurable via attaching methacrylate groups to the hydroxyl end groups of the small molecular weight prepolymer. This resin cures easily under UV irradiation, using a mercury lamp, and under femtosecond IR irradiation. The results showed that the photocurable polylactide (PLA) resin can be readily structured via direct laser write (DLW) with a femtosecond Ti:sapphire laser and submicrometer structures can be produced. The maximum resolution achieved is 800 nm. Neuroblastoma cells were grown on thin films of the cured PLA material, and cell viability and proliferation assays revealed good biocompatibility of the material. Additionally, PC12 and NG108-15 neuroblastoma growth on bespoke scaffolds was studied in more detail to assess potential applications for neuronal implants of this material.
TL;DR: It is shown that certain magnesium phosphate phases such as newberyite and cattiite are able to promote in vivo osteogenic activity in a similar way to calcium phosphates such as hydroxyapatite and brushite, which confirms the great potential of magnesium phosphate ceramics in the development of new biomaterials for bone regeneration.
TL;DR: The results suggest that such redox-responsive polyphosphate micelles can rapidly deliver anticancer drugs into the nuclei of tumor cells enhancing the inhibition of cell proliferation and provide a favorable platform to construct excellent drug delivery systems for cancer therapy.
TL;DR: It was observed that, by increasing the NCO:OH ratio, the average pore size, compressive strength, and compressive modulus increased, and the quality of samples exhibited suitable cell attachment and growth, with a high level of biocompatibility.
Abstract: Background Biodegradable polyurethanes have found widespread use in soft tissue engineering due to their suitable mechanical properties and biocompatibility. Methods In this study, polyurethane samples were synthesized from polycaprolactone, hexamethylene diisocyanate, and a copolymer of 1,4-butanediol as a chain extender. Polyurethane scaffolds were fabricated by a combination of liquid-liquid phase separation and salt leaching techniques. The effect of the NCO:OH ratio on porosity content and pore morphology was investigated. Results Scanning electron micrographs demonstrated that the scaffolds had a regular distribution of interconnected pores, with pore diameters of 50-300 μm, and porosities of 64%-83%. It was observed that, by increasing the NCO:OH ratio, the average pore size, compressive strength, and compressive modulus increased. L929 fibroblast and chondrocytes were cultured on the scaffolds, and all samples exhibited suitable cell attachment and growth, with a high level of biocompatibility. Conclusion These biodegradable polyurethane scaffolds demonstrate potential for soft tissue engineering applications.
TL;DR: A large-scale, cost-effective, and environmentally friendly synthetic strategy for biocompatible reduced graphene oxide (RGO) by using dextran as a reducing and stabilization agent has been developed.
TL;DR: Sub-50 nm pegylated mesoporous silica nanoparticles prepared with hydrothermal treatment show significantly improved biocompatibility and decreased macrophage uptake, making these nanoparticles viable for in vivo stealth drug delivery applications.
TL;DR: Chitosan is a natural polysaccharide exhibiting excellent biocompatibility, biodegradability, affinity to biomolecules, and wound-healing activity.
Abstract: Tissue repair and regeneration is an interdisciplinary field focusing on development of biological and bioactive substitutes. Chitosan is a natural polysaccharide exhibiting excellent biocompatibility, biodegradability, affinity to biomolecules, and wound-healing activity. It can also be easily modified via chemical and physical reactions to obtain derivatives of various structures, properties, functions, and applications. This paper focuses on chitosan and its derivatives as biomaterials for tissue repair and regeneration. Tuning the structure and properties such as biodegradability, mechanical strength, gelation property, and cell affinity can be achieved through chemical reaction, immobilization of specific ligands such as peptide and sugar molecules, combination with other biomaterials, and chemical or physical crosslinking. To obtain applicable three-dimensional scaffolding materials such as porous sponges, hydrogels, and rods, the formulation and stimuli-responsiveness of this material can also be modified. Moreover, chitosan and its derivatives can function as vectors for delivery of cell growth factors and particularly of functional genes encoding cell growth factors, which are easier to integrate with the formulated materials to obtain scaffolds of higher activity. Recent studies have shown that such scaffolds are of particular importance in mediating the proliferation, migration, and differentiation of stem cells. Finally, integration of chitosan with cell growth factors and associated genes and/or with cells (stem cells) produces chitosan-based biomaterials with applications in repair or regeneration of skin, cartilage, bone, and other tissue.
TL;DR: The dorsal skinfold chamber model does not only provide deep insights into the complex interactions of biomaterials with the surrounding soft tissues of the host but also represents an important tool for the future development of novel biommaterials aiming at an optimisation of their biofunctionality in clinical practice.
Abstract: The implantation of biomaterials into the human body has become an indispensable part of almost all fields of modern medicine. Accordingly, there is an increasing need for appropriate approaches, which can be used to evaluate the suitability of different biomaterials for distinct clinical indications. The dorsal skinfold chamber is a sophisticated experimental model, which has been proven to be extremely valuable for the systematic in vivo analysis of the dynamic interaction of small biomaterial implants with the surrounding host tissue in rats, hamsters and mice. By means of intravital fluorescence microscopy, this chronic model allows for repeated analyses of various cellular, molecular and microvascular mechanisms, which are involved in the early inflammatory and angiogenic host tissue response to biomaterials during the initial 2-3 weeks after implantation. Therefore, the dorsal skinfold chamber has been broadly used during the last two decades to assess the in vivo performance of prosthetic vascular grafts, metallic implants, surgical meshes, bone substitutes, scaffolds for tissue engineering, as well as for locally or systemically applied drug delivery systems. These studies have contributed to identify basic material properties determining the biocompatibility of the implants and vascular ingrowth into their surface or internal structures. Thus, the dorsal skinfold chamber model does not only provide deep insights into the complex interactions of biomaterials with the surrounding soft tissues of the host but also represents an important tool for the future development of novel biomaterials aiming at an optimisation of their biofunctionality in clinical practice.
TL;DR: PLGA microspheres have a strong capacity to induce fast degradation of injectable CPC and concomitant replacement by bone tissue by controlled release of acid polymeric degradation products without compromising the excellent biocompatibility and osteoconductivity of the CPC matrix.
TL;DR: Alginate-polycation interactions for membrane formation are more important for biocompatibility than either the quantity of polycation at the surface or the alginate coating.
TL;DR: In this paper, the authors highlight some general strategies to generate magnetic nanoparticle-based multifunctional nanostructures for biomedical applications such as bacterial detection, protein purification, enzyme immobilization, contamination decorporation, drug delivery, hyperthermia etc.
Abstract: Nanotechnology offers tremendous potential for future medical diagnosis and therapy. Various types of nanoparticles have been extensively studied for numerous biochemical and biomedical applications. Magnetic nanoparticles are well-established nanomaterials that offer controlled size, ability to be manipulated by an external magnetic field, and enhancement of contrast in magnetic resonance imaging. As a result, these nanoparticles could have many applications including bacterial detection, protein purification, enzyme immobilization, contamination decorporation, drug delivery, hyperthermia, etc. All these biochemical and biomedical applications require that these nanoparticles should satisfy some prerequisites including high magnetization, good stability, biocompatibility, and biodegradability. Because of the potential benefits of multimodal functionality in biomedical applications, in this account highlights some general strategies to generate magnetic nanoparticle-based multifunctional nanostructures. After these magnetic nanoparticles are conjugated with proper ligands (e.g., nitrilotriacetate), polymers (e.g., polyacrylic acid, chitosan, temperature- and pH-sensitive polymers), antibodies, enzymes, and inorganic metals (e.g., gold), such biofunctional magnetic nanoparticles exhibit many advantages in biomedical applications. In addition, the multifunctional magnetic nanoparticles have been widely applied in biochemical fields including enzyme immobilization and protein purification.
TL;DR: The results suggest that these micelle-drug conjugates could be a promising candidate for the delivery of anticancer agents with low side effects on normal cells and excellent therapeutic efficacy to cancer cells.
TL;DR: A comparison among all surface treatments showed that an incubation of the Mg samples in cell culture medium gave the lowest dissolution rate and resulted in the best cell adhesion and spreading behavior.
TL;DR: The dynamic rheological properties of the polymer mixtures during gelation indicated that the hydrogel mixtures with low storage moduli provided uniform nanofiber formation without beaded structures, which resulted in a lower swelling ratio and these nanofibrous scaffolds exhibit increased cell adhesion and proliferation compared to those made of alginate alone.
Abstract: Electrospun natural biopolymers are of great interest in the field of regenerative medicine due to their unique structure, biocompatibility, and potential to support controlled release of bioactive agents and/or the growth of cells near a site of interest. The ability to electrospin chitosan and alginate to form polyionic complexed nanofibrous scaffolds was investigated. These nanofibers crosslink in situ during the electrospinning process, and thus do not require an additional chemical crosslinking step. Although poly(ethylene oxide) (PEO) is required for the electrospinning, it can be subsequently removed from the nanofibers simply by incubating in water for a few days, as confirmed by attenuated total reflectance Fourier transform infrared. Solutions that allowed uniform nanofiber formation were found to have viscosities in the range of 0.15–0.7 Pa·s and conductivities below 4 mS/cm for chitosan-PEO and below 2.2 mS/cm for alginate-PEO. The resultant nanofibers both before and after PEO extraction were...
TL;DR: It is accurate to trace the first thinking about how a material should appropriately perform in an implant situation to about 1970, and the reaction called “biocompatibility” seems quite the opposite of biocompatible.
Abstract: A number of papers appeared in the 1940s, 1950s, and 1960s examining the tissue reaction to implanted biomaterials (for example, see [1]). Though many of these early observations were accurate, the word “biocompatible” was never used. By 1970, a few papers appeared that used the word “biocompatible.” According to the biocompatibility article in Wikipedia, “The word biocompatibility seems have been mentioned for the first time in peer-review journals and meetings in 1970 by RJ Hegyeli (Amer Chem Soc Annual Meeting abstract) and CA Homsy et al. (J Macromol Sci Chem A4:3,615,1970).” Thus, I believe it is accurate to trace the first thinking about how a material should appropriately perform in an implant situation to about 1970. The nature of this “appropriate reaction” we call “biocompatibility” is expanded upon in the next section of this article.
Over the years, many definitions have been offered for biocompatibility. The most widely cited of these originated at a consensus conference on biomaterials held in Chester, UK in 1986. Biocompatibility is
“the ability of a material to perform with an appropriate host response in a specific application [2]”
Though accurate and philosophically useful, this definition provides no insights for how to assess biocompatibility or how to enhance it. An update of this definition was recently offered that acknowledges the biological reaction:
Biocompatibility "refers to the ability of a biomaterial to perform its desired function with respect to a medical therapy, without eliciting any undesirable local or systemic effects in the recipient or beneficiary of that therapy, but generating the most appropriate beneficial cellular or tissue response in that specific situation, and optimising the clinically relevant performance of that therapy [3]"
This definition, though a step in the right direction, does not address the most compelling concern with biocompatibility today—the reaction we call “biocompatible” seems quite the opposite of biocompatible. This point is elaborated upon in the last section of this article.