Understanding Glass through Differential Scanning Calorimetry.

Differential scanning calorimetry (DSC) is a powerful tool to address some of the most challenging issues in glass science and technology, such as the nonequilibrium nature of the glassy state and the detailed thermodynamics and kinetics of glass-forming systems during glass transition, relaxation, rejuvenation, polyamorphic transition, and crystallization. The utility of the DSC technique spans across all glass-forming chemistries, including oxide, chalcogenide, metallic, and organic systems, as well as recently discovered metal-organic framework glass-forming systems. Here we present a comprehensive review of the many applications of DSC in glass science with focus on glass transition, relaxation, polyamorphism, and crystallization phenomena. We also emphasize recent advances in DSC characterization technology, including flash DSC and temperature-modulated DSC. This review demonstrates how DSC studies have led to a multitude of relevant advances in the understanding of glass physics, chemistry, and even technology.

The unexplored role of alkali and alkaline earth elements (ALAEs) on the structure, processing, and biological effects of bioactive glasses.

Bioactive glass has been employed in several medical applications since its inception in 1969. The compositions of these materials have been investigated extensively with emphasis on glass network formers, therapeutic transition metals, and glass network modifiers. Through these experiments, several commercial and experimental compositions have been developed with varying chemical durability, induced physiological responses, and hydroxyapatite forming abilities. In many of these studies, the concentrations of each alkali and alkaline earth element have been altered to monitor changes in structure and biological response. This review aims to discuss the impact of each alkali and alkaline earth element on the structure, processing, and biological effects of bioactive glass. We explore critical questions regarding these elements from both a glass science and biological perspective. Should elements with little biological impact be included? Are alkali free bioactive glasses more promising for greater biological responses? Does this mixed alkali effect show increased degradation rates and should it be employed for optimized dissolution? Each of these questions along with others are evaluated comprehensively and discussed in the final section where guidance for compositional design is provided.

Cobalt-Doped Bioactive Glasses for Biomedical Applications: A Review.

Improving angiogenesis is the key to the success of most regenerative medicine approaches. However, how and to which extent this may be performed is still a challenge. In this regard, cobalt (Co)-doped bioactive glasses show promise being able to combine the traditional bioactivity of these materials (especially bone-bonding and osteo-stimulatory properties) with the pro-angiogenic effect associated with the release of cobalt. Although the use and local delivery of Co2+ ions into the body have raised some concerns about the possible toxic effects on living cells and tissues, important biological improvements have been highlighted both in vitro and in vivo. This review aims at providing a comprehensive overview of Co-releasing glasses, which find biomedical applications as various products, including micro- and nanoparticles, composites in combination with biocompatible polymers, fibers and porous scaffolds. Therapeutic applications in the field of bone repair, wound healing and cancer treatment are discussed in the light of existing experimental evidence along with the open issues ahead.

Trends and perspectives on the commercialization of bioactive glasses.

At least 25 bioactive glass (BG) medical devices have been approved for clinical use by global regulatory agencies. Diverse applications include monolithic implants, bone void fillers, dentin hypersensitivity agents, wound dressing, and cancer therapeutics. The morphology and delivery systems of bioactive glasses have evolved dramatically since the first devices based on 45S5 Bioglass®. The particle size of these devices has generally decreased with the evolution of bioactive glass technology but primarily lies in the micron size range. Morphologies have progressed from glass monoliths to granules, putties, and cements, allowing medical professionals greater flexibility and control. Compositions of these commercial materials have primarily relied on silicate-based systems with varying concentrations of sodium, calcium, and phosphorus. Furthermore, therapeutic ions have been investigated and show promise for greater control of biological stimulation of genetic processes and increased bioactivity. Some commercial products have exploited the borate and phosphate-based compositions for soft tissue repair/regeneration. Mesoporous BGs also promise anticancer therapies due to their ability to deliver drugs in combination with radiotherapy, photothermal therapy, and magnetic hyperthermia. The objective of this article is to critically discuss all clinically approved bioactive glass products. Understanding essential regulatory standards and rules for production is presented through a review of the commercialization process. The future of bioactive glasses, their promising applications, and the challenges are outlined. STATEMENT OF SIGNIFICANCE: Bioactive glasses have evolved into a wide range of products used to treat various medical conditions. They are non-equilibrium, non-crystalline materials that have been designed to induce specific biological activity. They can bond to bone and soft tissues and contribute to their regeneration. They are promising in combating pathogens and malignancies by delivering drugs, inorganic therapeutic ions, and heat for magnetic-induced hyperthermia or laser-induced phototherapy. This review addresses each bioactive glass product approved by regulatory agencies for clinical use. A review of the commercialization process is also provided with insight into critical regulatory standards and guidelines for manufacturing. Finally, a critical evaluation of the future of bioactive glass development, applications, and challenges are discussed.

Physicochemical, Morphological, and Cytotoxic Properties of Brazilian Jackfruit (Artocarpus heterophyllus) Starch Scaffold Loaded with Silver Nanoparticles.

Due to the physical, thermal, and biological properties of silver nanoparticles (AgNPs), as well as the biocompatibility and environmental safety of the naturally occurring polymeric component, polysaccharide-based composites containing AgNPs are a promising choice for the development of biomaterials. Starch is a low-cost, non-toxic, biocompatible, and tissue-healing natural polymer. The application of starch in various forms and its combination with metallic nanoparticles have contributed to the advancement of biomaterials. Few investigations into jackfruit starch with silver nanoparticle biocomposites exist. This research intends to explore the physicochemical, morphological, and cytotoxic properties of a Brazilian jackfruit starch-based scaffold loaded with AgNPs. The AgNPs were synthesized by chemical reduction and the scaffold was produced by gelatinization. X-ray diffraction (XRD), differential scanning calorimetry (DSC), scanning electron microscopy coupled with energy-dispersive spectroscopy (SEM-EDS), and Fourier-transform infrared spectroscopy (FTIR) were used to study the scaffold. The findings supported the development of stable, monodispersed, and triangular AgNPs. XRD and EDS analyses demonstrated the incorporation of silver nanoparticles. AgNPs could alter the scaffold's crystallinity, roughness, and thermal stability without affecting its chemistry or physics. Triangular anisotropic AgNPs exhibited no toxicity against L929 cells at concentrations ranging from 6.25 × 10-5 to 1 × 10-3 mol·L-1, implying that the scaffolds might have had no adverse effects on the cells. The scaffolds prepared with jackfruit starch showed greater crystallinity and thermal stability, and absence of toxicity after the incorporation of triangular AgNPs. These findings indicate that jackfruit is a promising starch source for developing biomaterials.

Chitosan-PEG Gels Loaded with Jatropha mollissima (Pohl) Baill. Ethanolic Extract: An Efficient and Effective Biomaterial in Hemorrhage Control.

A lack of control over blood loss can have catastrophic implications, including death. Although several hemostatic medications have been employed to reduce bleeding, a vast majority of them are ineffective, expensive, or pose health risks to the patient. To overcome these constraints, chitosan-polyethylene glycol (CS-PEG) hemostatic gels loaded with ethanolic extract of Jatropha mollissima sap (EES) were prepared and their hemostatic, physicochemical, and cytotoxic properties were evaluated. The gels were produced by mixing CS with PEG (an external plasticizer) and EES. The phytochemical analysis revealed a significant concentration of total polyphenols and tannins content in the extract and catechin was identified as one of the key compounds of EES. Infrared spectroscopy analysis revealed the presence of EES in the gels, as well as the chemical interaction between CS and PEG. The gels were thermally stable between 25 and 37 °C (ambient and human body temperature range), had pseudoplastic deformation behavior (rheological properties preserved after shearing), were simple to inject (compression force 30 N), and were biocompatible. In vivo experiments showed that both CS-PEG-EES gels exhibited greater hemostatic action in preventing tail hemorrhage in Wistar rats, with decreased bleeding time and blood weight compared with unloaded CS-PEG gels (control groups) and Hemostank, a commercial product. However, the gel prepared with acetic acid was more efficient in controlling bleeding. These findings reveal that CS-PEG-EES gels can reduce hemorrhages and are a potent, simple, and safe hemostatic agent.

Gelatin and Bioactive Glass Composites for Tissue Engineering: A Review.

Nano-/micron-sized bioactive glass (BG) particles are attractive candidates for both soft and hard tissue engineering. They can chemically bond to the host tissues, enhance new tissue formation, activate cell proliferation, stimulate the genetic expression of proteins, and trigger unique anti-bacterial, anti-inflammatory, and anti-cancer functionalities. Recently, composites based on biopolymers and BG particles have been developed with various state-of-the-art techniques for tissue engineering. Gelatin, a semi-synthetic biopolymer, has attracted the attention of researchers because it is derived from the most abundant protein in the body, viz., collagen. It is a polymer that can be dissolved in water and processed to acquire different configurations, such as hydrogels, fibers, films, and scaffolds. Searching "bioactive glass gelatin" in the tile on Scopus renders 80 highly relevant articles published in the last ~10 years, which signifies the importance of such composites. First, this review addresses the basic concepts of soft and hard tissue engineering, including the healing mechanisms and limitations ahead. Then, current knowledge on gelatin/BG composites including composition, processing and properties is summarized and discussed both for soft and hard tissue applications. This review explores physical, chemical and mechanical features and ion-release effects of such composites concerning osteogenic and angiogenic responses in vivo and in vitro. Additionally, recent developments of BG/gelatin composites using 3D/4D printing for tissue engineering are presented. Finally, the perspectives and current challenges in developing desirable composites for the regeneration of different tissues are outlined.

Radiopaque Crystalline, Non-Crystalline and Nanostructured Bioceramics.

Radiopacity is sometimes an essential characteristic of biomaterials that can help clinicians perform follow-ups during pre- and post-interventional radiological imaging. Due to their chemical composition and structure, most bioceramics are inherently radiopaque but can still be doped/mixed with radiopacifiers to increase their visualization during or after medical procedures. The radiopacifiers are frequently heavy elements of the periodic table, such as Bi, Zr, Sr, Ba, Ta, Zn, Y, etc., or their relevant compounds that can confer enhanced radiopacity. Radiopaque bioceramics are also intriguing additives for biopolymers and hybrids, which are extensively researched and developed nowadays for various biomedical setups. The present work aims to provide an overview of radiopaque bioceramics, specifically crystalline, non-crystalline (glassy), and nanostructured bioceramics designed for applications in orthopedics, dentistry, and cancer therapy. Furthermore, the modification of the chemical, physical, and biological properties of parent ceramics/biopolymers due to the addition of radiopacifiers is critically discussed. We also point out future research lacunas in this exciting field that bioceramists can explore further.

Multiple and Promising Applications of Strontium (Sr)-Containing Bioactive Glasses in Bone Tissue Engineering.

Improving and accelerating bone repair still are partially unmet needs in bone regenerative therapies. In this regard, strontium (Sr)-containing bioactive glasses (BGs) are highly-promising materials to tackle this challenge. The positive impacts of Sr on the osteogenesis makes it routinely used in the form of strontium ranelate (SR) in the clinical setting, especially for patients suffering from osteoporosis. Therefore, a large number of silicate-, borate-, and phosphate-based BGs doped with Sr and produced in different shapes have been developed and characterized, in order to be used in the most advanced therapeutic strategies designed for the management of bone defects and injuries. Although the influence of Sr incorporation in the glass is debated regarding the obtained physicochemical and mechanical properties, the biological improvements have been found to be substantial both in vitro and in vivo. In the present study, we provide a comprehensive overview of Sr-containing glasses along with the current state of their clinical use. For this purpose, different types of Sr-doped BG systems are described, including composites, coatings and porous scaffolds, and their applications are discussed in the light of existing experimental data along with the significant challenges ahead.

Mesoporous bioactive glasses: Promising platforms for antibacterial strategies.

The control of bacterial infections is of particular importance in the field of tissue engineering. Recently, much attention has been addressed toward the use of mesoporous bioactive glasses (MBGs) for antibacterial strategies, primarily because of their capability of acting as carriers for the local release of antimicrobial agents. The incorporation of antibacterial metallic ions including silver (Ag+), zinc (Zn2+), copper (Cu+ and Cu2+), cerium (Ce3+ and Ce4+), and gallium (Ga3+) cations into the MBG structure and their controlled release is proposed as one of the most attractive strategies for inhibiting bacterial growth and reproduction. Moreover, the possibility of loading and delivering various antibacterial biomolecules (e.g., antibiotics) through the porous structure of MBGs makes them as ideal candidates for antibacterial applications. In this review, we aim to present a comprehensive evaluation of MBG potential regarding antibacterial activities. For this purpose, different types of antibacterial ion-doped and drug-loaded MBGs are introduced and discussed in the light of existing knowledge, along with the significant challenges ahead. STATEMENT OF SIGNIFICANCE: Prevention and treatment of infections is one of the today's greatest challenges in medical sciences, also considering the well-known issues related to increased bacterial resistance to antibiotics. The advent of mesoporous glasses led to the birth of a new class of multifunctional biomaterials acting as bioactive platforms for the local release of organic or inorganic agents eliciting an antimicrobial effect. This reviews summarizes the state of the art of MBGs in this field, highlighting the latest evolutions and the specific role played by metallic antimicrobial ions that can be incorporated in the glass composition and then properly released. Perspective for tissue engineering applications are also discussed to provide an up-to-date contribution that is useful to both experienced scientists and early-stage researchers.

Bioactive and inert dental glass-ceramics.

The global market for dental materials is predicted to exceed 10 billion dollars by 2020. The main drivers for this growth are easing the workflow of dentists and increasing the comfort of patients. Therefore, remarkable research projects have been conducted and are currently underway to develop improved or new dental materials with enhanced properties or that can be processed using advanced technologies, such as CAD/CAM or 3D printing. Among these materials, zirconia, glass or polymer-infiltrated ceramics, and glass-ceramics (GCs) are of great importance. Dental glass-ceramics are highly attractive because they are easy to process and have outstanding esthetics, translucency, low thermal conductivity, high strength, chemical durability, biocompatibility, wear resistance, and hardness similar to that of natural teeth, and, in certain cases, these materials are bioactive. In this review article, we divide dental GCs into the following two groups: restorative and bioactive. Most restorative dental glass-ceramics (RDGCs) are inert and biocompatible and are used in the restoration and reconstruction of teeth. Bioactive dental glass-ceramics (BDGCs) display bone-bonding ability and stimulate positive biological reactions at the material/tissue interface. BDGCs are suggested for dentin hypersensitivity treatment, implant coating, bone regeneration and periodontal therapy. Throughout this paper, we elaborate on the history, processing, properties and applications of RDGCs and BDGCs. We also report on selected papers that address promising types of dental glass-ceramics. Finally, we include trends and guidance on relevant open issues and research possibilities. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 619-639, 2017.

History and trends of bioactive glass-ceramics.

The interest around bioactive glass-ceramics (GCs) has grown significantly over the last two decades due to their appropriate biochemical and mechanical properties. The intense research effort in this field has led to some new commercial products for biomedical applications. This review article begins with the basic concepts of GC processing and development via controlled heat treatments of monolithic pieces or sinter-crystallization of powdered glasses. We then go on to describe the processing, properties, and applications of some commercial bioactive GCs and discuss selected valuable reported researches on several promising types of bioactive GCs. The article finishes with a section on open relevant research directions for bioactive GC development.

Bioactivity and cell proliferation in radiopaque gel-derived CaO-P2O5-SiO2-ZrO2 glass and glass-ceramic powders.

In this study, 10 mol% ZrO2 was added to a 27CaO-5P2O5-68SiO2 (mol%) base composition synthesized via a simple sol-gel method. This composition is similar to that of a frequently investigated bioactive gel-glass. The effects of ZrO2 on the in vitro bioactivity and MG-63 cell proliferation of the glass and its derivative polycrystalline (glass-ceramic) powder were investigated. The samples were characterized using thermo-gravimetric and differential thermal analysis (TG/DTA), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) coupled to energy dispersive X-ray spectroscopy (EDS). Release of Si, Ca, P and Zr into simulated body fluid (SBF) was determined by inductively coupled plasma (ICP). Upon heat treatment at 1000 °C, the glass powder crystallized into an apatite-wollastonite-zirconia glass-ceramic powder. Hydroxycarbonate apatite (HCA) formation on the surface of the glass and glass-ceramic particles containing ZrO2 was confirmed by FTIR and SEM. Addition of ZrO2 to the base glass composition decreased the rate of HCA formation in vitro from one day to three days, and hence, ZrO2 could be employed to control the rate of apatite formation. However, the rate of HCA formation on the glass-ceramic powder containing ZrO2 crystal was equal to that in the base glassy powder. Tests with a cultured human osteoblast-like MG-63 cells revealed that the glass and glass-ceramic materials stimulated cell proliferation, indicating that they are biocompatible and are not cytotoxic in vitro. Moreover, zirconia clearly increased osteoblast proliferation over that of the Zr-free samples. This increase is likely associated with the lower solubility of these samples and, consequently, a smaller variation in the media pH. Despite the low solubility of these materials, bioactivity was maintained, indicating that these glassy and polycrystalline powders are potential candidates for bone graft substitutes and bone cements with the special feature of radiopacity.