Globally, chronic wounds impose a notable burden to patients and healthcare systems. Such skin wounds are readily subjected to bacteria that provoke inflammation and hence challenge the healing ...process. Furthermore, bacteria induce infection impeding re-epithelialization and collagen synthesis. With an estimated global market of $20.4 billion by 2021, appropriate wound dressing materials e.g. those composed of biopolymers originating from nature, are capable of alleviating the infection incidence and of accelerating the healing process. Particularly, biopolymeric nanofibrous dressings are biocompatible and mostly biodegradable and biomimic the extracellular matrix structure. Such nanofibrous dressings provide a high surface area and the ability to deliver antibiotics and antibacterial agents locally into the wound milieu to control infection. In this regard, with the dangerous evolution of antibiotic resistant bacteria, antibiotic delivery systems are being gradually replaced with antibacterial biohybrid nanofibrous wound dressings. This emerging class of wound dressings comprises biopolymeric nanofibers containing antibacterial nanoparticles, nature-derived compounds and biofunctional agents. Here, the most recent (since 2015) developments of antibacterial biopolymeric nanofibrous wound dressings, particularly those made of biohybrids, are reviewed and their antibacterial efficiency is evaluated based on a comprehensive literature analysis. Lastly, the prospects and challenges are discussed to draw a roadmap for further progresses and to open up future research avenues in this area.
With a global market of $20.4 billion by 2021, skin wound dressings are a crucial segment of the wound care industry. As an advanced class of bioactive wound dressing materials, natural polymeric nanofibers loaded with antibacterial agents, e.g. antimicrobial nanoparticles/ions, nature-derived compounds and biofunctional agents, have shown a remarkable potential for replacement of their classic counterparts. Also, given the expanding concern regarding antibiotic resistant bacteria, such biohybrid nanofibrous wound dressings can outperform classical drug delivery systems. Here, an updated overview of the most recent (since 2015) developments of antibacterial biopolymeric nanofibrous wound dressings is presented. In this review, while discussing about the antibacterial efficiency of such systems, the prospects and challenges are highlighted to draw a roadmap for further progresses in this area.
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Electrically conductive biomaterials are gaining increasing interest owing to their potential to be used in smart, biosensoric and functional tissue-engineered scaffolds and implants. ...In combination with 3D printing technology, this class of materials might be one of the most advanced approaches towards future medical implants regarding potential functionalities and design possibilities. Conductive hydrogels themselves have been researched for potential sensoric and tissue engineering applications for more than a decade, while the 3D printing of such functional materials is still under early exploration. This review aims to provide a short insight into the most recent developments of 3D printable and electrically conductive hydrogels. It also provides a summary of the last few years of research in this field, with key scope on 3D printing for biomedical applications. The final literature search was conducted in May 2019, with the specific keywords ‘3D’, ‘printing’, ‘conductive’, ‘hydrogel’, ‘biocompatible’ and combinations of the latter, using advanced search in the databases Scopus®, Web of Science® (Web of Knowledge®) and Google Scholar®. A total of 491 results were gained, while 19 recent publications were identified with the above-mentioned criteria and keywords, which are the studies finally discussed in the paper. The key results have been summarised, and the remaining challenges in the field and the scope for future research activities have been discussed.
Hydrogels are among the most frequently used biomaterials in tissue engineering (TE). A new class of hydrogels, namely, electrically conductive hydrogels (ECHs), has been introduced in recent years. Although ECHs have been comprehensively reviewed in the literature, the combination of ECHs with 3D printing technology has emerged only recently, representing a promising key development toward the fabrication of functional 3D TE constructs. In this review, we cover for the first time the state of the art in the field of 3D printing of ECHs. Previous advances are presented, reviewing the 3D printing technologies utilised, spatial resolution and electrical conductivity values achieved, in addition to discussing the obtained mechanical properties and emerging applications of these materials.
Silicate-based bioactive glass nanoparticles (BGN) are gaining increasing attention in various biomedical applications due to their unique properties. Controlled synthesis of BGN is critical to their ...effective use in biomedical applications since BGN characteristics, such as morphology and composition, determining the properties of BGN, are highly related to the synthesis process. In the last decade, numerous investigations focusing on BGN synthesis have been reported. BGN can mainly be produced through the conventional melt-quench approach or by sol-gel methods. The latter approaches are drawing widespread attention, considering the convenience and versatility they offer to tune the properties of BGN. In this paper, we review the strategies of sol-gel processing of BGN, including those adopting different catalysts for initiating the hydrolysis and condensation of silicate precursors as well as those combining sol-gel chemistry with other techniques. The processes and mechanism of different synthesis approaches are introduced and discussed in detail. Considering the importance of the BGN morphology and composition to their biomedical applications, strategies put forward to control the size, shape, pore structure and composition of BGN are discussed. BGN are particularly interesting biomaterials for bone-related applications, however, they also have potential for other biomedical applications, e.g. in soft tissue regeneration/repair. Therefore, in the last part of this review, recently reported applications of BGN in soft tissue repair and wound healing are presented.
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•Sol-gel based approaches for BGN synthesis reviewed•Comparison of different sol-gel based methods for BGN production•Parameters controlling size, shape, porosity and composition of BGN discussed•Overview of biomedical applications of BGN besides bone regeneration
This review summarizes different types of industrial wastes such as biomass ash, red mud, recycled glass and heavy metals waste, in their application for geopolymer production. These wastes, which ...are currently abundant and urgent to dispose of, cannot be used alone in the geopolymer process because they do not provide a suitable SiO2/Al2O3 molar ratio for this technology. For this reason, these by-products are commonly used in addition to other aluminosilicate sources such as fly ash or metakaolin. Important parameters which affect the properties and performance of fly ash based geopolymers with addition of a variety of wastes are discussed based on a comprehensive literature review.
Oxidized alginate (OA)-based hydrogels have drawn considerable attention as biodegradable materials for tissue engineering applications. OA possesses a faster degradation rate and contains more ...reactive groups compared to native alginate. This review summarizes the research publications reporting the development of OA-based hydrogels for tissue engineering applications including bone, cartilage, blood vessel, cornea, and other soft tissues, highlighting OA key properties and processing approaches.
There is a growing demand for three-dimensional scaffolds for expanding applications in regenerative medicine, tissue engineering, and cell culture techniques. The material requirements for such ...three-dimensional structures are as diverse as the applications themselves. A wide range of materials have been investigated in the recent decades in order to tackle these requirements and to stimulate the anticipated biological response. Among the most promising class of materials are inorganic/organic hydrogel composites for regenerative medicine. The generation of synergetic effects by hydrogel composite systems enables the design of materials with superior properties including biological performance, stiffness, and degradation behavior in vitro and in vivo. Here, we review the most important organic and inorganic materials used to fabricate hydrogel composites. We highlight the advantages of combining different materials with respect to their use for biofabrication and cell encapsulation as well as their application as injectable materials for tissue enhancement and regeneration.
The growing demand for personalized implants and tissue scaffolds requires advanced biomaterials and processing strategies for the fabrication of three-dimensional (3D) structures mimicking the ...complexity of the extracellular matrix. During the last years, biofabrication approaches like 3D printing of cell-laden (soft) hydrogels have been gaining increasing attention to design such 3D functional environments which resemble natural tissues (and organs). However, often these polymeric hydrogels show poor stability and low printing fidelity and hence various approaches in terms of multi-material mixtures are being developed to enhance pre- and post-printing features as well as cytocompatibility and post-printing cellular development. Additionally, bioactive properties improve the binding to the surrounding (host) tissue at the implantation site. In this review we focus on the state-of-the-art of a particular type of heterogeneous bioinks, which are composed of polymeric hydrogels incorporating inorganic bioactive fillers. Such systems include isotropic and anisotropic silicates like bioactive glasses and nanoclays or calcium-phosphates like hydroxyapatite (HAp), which provide in-situ crosslinking effects and add extra functionality to the matrix, for example mineralization capability. The present review paper discusses in detail such bioactive composite bioink systems based on the available literature, revealing that a great variety has been developed with substantially improved bioprinting characteristics, in comparison to the pure hydrogel counterparts, and enabling high viability of printed cells. The analysis of the results of the published studies demonstrates that bioactive fillers are a promising addition to hydrogels to print stable 3D constructs for regeneration of tissues. Progress and challenges of the development and applications of such composite bioink approaches are discussed and avenues for future research in the field are presented.
Biofabrication, involving the processing of biocompatible hydrogels including cells (bioinks), is being increasingly applied for developing complex tissue and organ mimicking structures. A variety of multi-material bioinks is being investigated to bioprint 3D constructs showing shape stability and long-term biological performance. Composite hydrogel bioinks incorporating inorganic bioreactive fillers for 3D bioprinting are the subject of this review paper. Results reported in the literature highlight the effect of bioactive fillers on bioink properties, printability and on cell behavior during and after printing and provide important information for optimizing the design of future bioinks for biofabrication, exploiting the extra functionalities provided by inorganic fillers. Further functionalization with drugs/growth factors can target enhanced printability and local drug release for more specialized biomedical therapies.
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Mesoporous silica-based materials, especially mesoporous bioactive glasses (MBGs), are being highly considered for biomedical applications, including drug delivery and tissue engineering, not only ...because of their bioactivity and biocompatibility but also due to their tunable composition and potential use as drug delivery carriers owing to their controllable nanoporous structure. Numerous researches have reported that MBGs can be doped with various therapeutic ions (strontium, copper, magnesium, zinc, lithium, silver, etc.) and loaded with specific biomolecules (e.g., therapeutic drugs, antibiotics, growth factors) achieving controllable loading and release kinetics. Therefore, co-delivery of ions and biomolecules using a single MBG carrier is highly interesting as this approach provides synergistic effects toward improved therapeutic outcomes in comparison to the strategy of sole drug or ion delivery. In this review, we discuss the state-of-the-art in the field of mesoporous silica-based materials used for co-delivery of ions and therapeutic drugs with osteogenesis/cementogenesis, angiogenesis, antibacterial and anticancer properties. The analysis of the literature reveals that specially designed mesoporous nanocarriers can release multiple ions and drugs at therapeutically safe and relevant levels, achieving the desired biological effects (in vivo, in vitro) for specific biomedical applications. It is expected that this review on the ion/drug co-delivery concept using MBG carriers will shed light on the advantages of such co-delivery systems for clinical use. Areas for future research directions are identified and discussed.
Many studies in literature focus on the potential of single drug or ion delivery by mesoporous silica-based materials, exploiting the bioactivity, biocompatibility, tunable composition and controllable nanoporosity of these materials. Recenlty, studies have adopted the “dual-delivery” concept, by designing multi-functional mesoporous silica-based systems which are capable to deliver both biologically active ions and biomolecules (growth factors, drugs) simultaneously in order to achieve synergy of their complementary therapeutic activities. This review summarizes the state of the art in the field, with focus on osteogenesis/cementogenesis, angiogenesis, antibacterial and anticancer properties, and discusses the challenges and prospects for further progress in this area, expecting to generate broader interest in the technology for applications in disease treatment and regenerative medicine.
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Copper-containing bioactive glass nanoparticles (Cu-BG NPs) with designed compositions and sizes were synthesized and incorporated into chitosan (CH)/silk fibroin ...(SF)/glycerophosphate (GP) composites to prepare injectable hydrogels for cell-free bone repair. The resulting Cu-BG/CH/SF/GP gels were found to exhibit well-defined injectability and to undergo rapid gelation at physiological temperature and pH. They were highly porous and showed the ability to administer Si, Ca and Cu ions at their respective safe doses in a sustained and controlled manner. In vitro studies revealed that the gels supported the growth of seeded MC3T3-E1 and human umbilical vein endothelial cells, and effectively induced them toward osteogenesis and angiogenesis, respectively. In vivo bone repair based on a critical-size rat calvarial bone defect model demonstrated that the optimal Cu-BG/CH/SF/GP gel was able to fully restore the bone defect with formation of vascularized bone tissue and mineralized collagen deposition during a treatment period of 8 weeks without utilization of any cells and/or growth factors. The results suggest that the presently developed Cu-BG/CH/SF/GP composite hydrogels have great potential and translation ability for bone regeneration owing to their thermo-sensitive properties, cell-free bioactivity, and cost-effectiveness.
Hydrogels loaded with cells and/or growth factors exhibit potential in bone repair. However, they have been facing obstacles related to the clinic translation. Here, a novel type of hydrogel system consisting of copper-containing bioactive glass nanoparticles and chitosan/silk fibroin composite was developed. These gels showed injectability and thermally triggered in situ gelation properties and were able to administer the release of ions at safe but effective doses in a controlled manner while inducing the seeded cells toward osteogenesis and angiogenesis. The optimal gel showed the ability to fully repair critical-size rat calvarial bone defects without involving time consuming cell processing and/or the use of expensive growth factors, confirming that this novel hydrogel system has great potential for translation to the clinic.
Abstract Several inorganic materials such as special compositions of silicate glasses, glass-ceramics and calcium phosphates have been shown to be bioactive and resorbable and to exhibit appropriate ...mechanical properties which make them suitable for bone tissue engineering applications. However, the exact mechanism of interaction between the ionic dissolution products of such inorganic materials and human cells are not fully understood, which has prompted considerable research work in the biomaterials community during the last decade. This review comprehensively covers literature reports which have investigated specifically the effect of dissolution products of silicate bioactive glasses and glass-ceramics in relation to osteogenesis and angiogenesis. Particularly, recent advances made in fabricating dense biomaterials and scaffolds doped with trace elements (e.g. Zn, Sr, Mg, and Cu) and investigations on the effect of these elements on the scaffold biological performance are summarized and discussed in detail. Clearly, the biological response to artificial materials depends on many parameters such as chemical composition, topography, porosity and grain size. This review, however, focuses only on the ion release kinetics of the materials and the specific effect of the released ionic dissolution products on human cell behaviour, providing also a scope for future investigations and identifying specific research needs to advance the field. The biological performance of pure and doped silicate glasses, phosphate based glasses with novel specific compositions as well as several other silicate based compounds are discussed in detail. Cells investigated in the reviewed articles include human osteoblastic and osteoclastic cells as well as endothelial cells and stem cells.