Current advances concerning the most cited metal ions doped bioceramics and silicate-based bioactive glasses for bone tissue engineering

Studies related to biomaterials that stimulate the repair of living tissue have increased considerably, improving the quality of many people's lives that require surgery due to traumatic accidents, bone diseases, bone defects, and reconstructions. Among these biomaterials, bioceramics and bioactive glasses (BGs) have proved to be suitable for coating materials, cement, scaffolds, and nanoparticles, once they present good biocompatibility and degradability, able to generate osteoconduction on the surrounding tissue. However, the role of biomaterials in hard tissue engineering is not restricted to a structural replacement or for guiding tissue regeneration. Nowadays, it is expected that biomaterials develop a multifunctional role when implanted, orchestrating the process of tissue regeneration and providing to the body the capacity to heal itself. In this way, the incorporation of specific metal ions in bioceramics and BGs structure, including magnesium, silver, strontium, lithium, copper, iron, zinc, cobalt, and manganese are currently receiving enhanced interest as biomaterials for biomedical applications. When an ion is incorporated into the bioceramic structure, a new category of material is created, which has several unique properties that overcome the disadvantages of primitive material and favors its use in different biomedical applications. The doping can enhance handling properties, angiogenic and osteogenic performance, and antimicrobial activity. Therefore, this review aims to summarize the effect of selected metal ion dopants into bioceramics and silicate-based BGs in bone tissue engineering. Furthermore, new applications for doped bioceramics and BGs are highlighted, including cancer treatment and drug delivery.     

Magnesium-Containing Bioactive Glasses for Biomedical Applications

The importance of Mg in the human body, its key role in bone tissue development, in addition to its application to improve and modify physical, thermal, and mechanical properties of bioactive silicate glasses, make Mg a very interesting element as a component of bioactive glasses for medical applications. Although Mg is a typical element in the composition of numerous developed bioactive glasses, the analysis of the literature reveals that further research is required to gain comprehensive understanding about the effects of MgO on bioactive glass structure and properties. This article presents a comprehensive overview of the field of Mg-containing bioactive glasses discussing available compositions and summarizing existing knowledge on effects of MgO on glass properties. The biomedical applications of several developed glasses are discussed highlighting the distinct effects of Mg in relevant areas, such as bioactivity and cell response, and focusing on the most common applications for these glasses, such as bone cements, bioactive coatings, and scaffolds for bone tissue engineering. The effect of Mg on bone development is discussed and avenues for future research in the field are proposed, emphasizing the need to investigate unstudied properties of (already developed) Mg-containing glass compositions, such as angiogenesis-stimulating action and the effect on osteoclast functions, to develop new Mg-containing bioactive glasses as well as to make products of different shape designs such as nanoparticles, fibers, and complex porous structures.     

In vitro and in vivo properties of graphene-incorporated scaffolds for bone defect repair

The employment of graphene and its derivatives, graphene oxide and reduced graphene oxide, is extending from bioimaging and fabrications of biosensors to drug delivery and tissue engineering in the biomedical area. Graphene family-incorporated scaffolds, used in bone tissue engineering and bone regenerative medicine, profit superior properties of these materials, such as enhanced mechanical properties, large surface area, and the existence of functional groups. At the same time, problems related to cytotoxicity and adverse immune response of graphene family are solved when they are applied to produce 3-dimensional scaffolds. The objective of this review is to focus on in vitro properties of scaffolds consisting of graphene or its derivatives, especially osteogenic and antibacterial properties, as well as the influence of graphene and its derivatives on in vivo performances of implanted bone scaffolds. The positive effect of graphene and its two derivatives on attachment, and cell proliferation, as well as in vitro osteogenic differentiation of different cells was undeniable. Besides, the synergetic outcome of using graphene family on the antibacterial feature of scaffolds, especially incorporation with the silver element, was effective. Moreover, successful treatment of critical-sized bone defects was reported during in vivo preclinical tests when graphene or its derivatives-incorporated scaffolds were used. However, the limited number of in vivo studies should be considered as one of the main shortcomings to use graphene as a promising candidate for treating bone defects. It is anticipated that the increased number of well-designed preclinical studies could improve the applications of graphene incorporated scaffolds in bone tissue engineering/regeneration, and find out explanations and appropriate solutions to possible long-term toxicity and nonbiodegradability of these materials.     

Electrospun polymeric nanofibers for dental applications

Electrospinning is an economical, efficient, and versatile process for the preparation of continuous nanofibers with desired patterns, tailored fiber diameters, and orientations. Since its invention, electrospinning has been utilized to prepare nanofibers from several natural polymers and synthetic polymers for use as scaffolds in tissue engineering, regeneration, and biomedical applications. Furthermore, complex scaffolds were prepared by electrospinning complex polymer solutions formulated by blending natural and synthetic organic polymers with bioceramics and other inorganic molecules. Lately, coaxial electrospinning has emerged as a promising technology in the preparation of drug-loaded biodegradable core-shell structured micro/nanofibers for sustained drug delivery applications. This paper will discuss the basic mechanism of electrospinning, parameters governing the electrospinning process, various materials investigated for use in the electrospinning process, and its recent advances.     

An Update on Graphene-Based Nanomaterials for Neural Growth and Central Nervous System Regeneration

Thanks to their reduced size, great surface area, and capacity to interact with cells and tissues, nanomaterials present some attractive biological and chemical characteristics with potential uses in the field of biomedical applications. In this context, graphene and its chemical derivatives have been extensively used in many biomedical research areas from drug delivery to bioelectronics and tissue engineering. Graphene-based nanomaterials show excellent optical, mechanical, and biological properties. They can be used as a substrate in the field of tissue engineering due to their conductivity, allowing to study, and educate neural connections, and guide neural growth and differentiation; thus, graphene-based nanomaterials represent an emerging aspect in regenerative medicine. Moreover, there is now an urgent need to develop multifunctional and functionalized nanomaterials able to arrive at neuronal cells through the blood-brain barrier, to manage a specific drug delivery system. In this review, we will focus on the recent applications of graphene-based nanomaterials in vitro and in vivo, also combining graphene with other smart materials to achieve the best benefits in the fields of nervous tissue engineering and neural regenerative medicine. We will then highlight the potential use of these graphene-based materials to construct graphene 3D scaffolds able to stimulate neural growth and regeneration in vivo for clinical applications.     

Application of 3D-Printed,PLGA-Based Scaffolds in Bone Tissue Engineering

Polylactic acid–glycolic acid (PLGA) has been widely used in bone tissue engineering due to its favorable biocompatibility and adjustable biodegradation. 3D printing technology can prepare scaffolds with rich structure and function, and is one of the best methods to obtain scaffolds for bone tissue repair. This review systematically summarizes the research progress of 3D-printed, PLGA-based scaffolds. The properties of the modified components of scaffolds are introduced in detail. The influence of structure and printing method change in printing process is analyzed. The advantages and disadvantages of their applications are illustrated by several examples. Finally, we briefly discuss the limitations and future development direction of current 3D-printed, PLGA-based materials for bone tissue repair.     

Novel 3D scaffolds of chitosan-PLLA blends for tissue engineering applications: Preparation and characterization

This work addresses the preparation of 3D porous scaffolds of blends of chitosan and poly(l-lactic acid), CHT and PLLA, using supercritical fluid technology. Supercritical assisted phase-inversion was used to prepare scaffolds for tissue engineering purposes. The physicochemical and biological properties of chitosan make it an excellent material for the preparation of drug delivery systems and for the development of new biomedical applications in many fields from skin to bone or cartilage regeneration. On the other hand, PLLA is a synthetic biodegradable polymer widely used for biomedical applications. Supercritical assisted phase-inversion experiments were carried out in samples with different polymer ratios and different polymer solution concentrations. The effect of CHT:PLLA ratio and polymer concentration and on the morphology and topography of the scaffolds was assessed by SEM and Micro-CT. Infra-red spectroscopic imaging analysis of the scaffolds allowed a better understanding on the distribution of the two polymers within the matrix. This work demonstrates that supercritical fluid technology constitutes a new processing technology, clean and environmentally friendly for the preparation of scaffolds for tissue engineering using these materials.     

Electrospun poly(aspartic acid) gel scaffolds for artificial extracellular matrix

Biocompatible synthetic polymer gel scaffolds for tissue engineering and regenerative medicine were prepared by reactive electrospinning. Protein‐like nano‐ and microfibres from chemically crosslinked polysuccinimide were obtained. Fibrous poly(aspartic acid) gels with size similar to that of extracellular matrix were obtained by hydrolysis of the polysuccinimide gel fibres. The effects of process parameters on fibre morphology (diameter, swelling degree) and chemical structure were investigated. Sub‐micrometre‐sized biocompatible fibrous scaffolds from a poly(amino acid) is a novel approach with great promise in several biomedical applications due to the tailor‐made synthetic nature, extreme purity and possibility of production on a large scale. © 2014 Society of Chemical Industry     

Thermal and dynamic mechanical behavior of poly(lactic acid) (PLA)-based electrospun scaffolds for tissue engineering

Electrospun scaffolds can find numerous applications, including biomedical; for example, tissue engineering. Poly-L-lactic acid is considered suitable for these applications, but its low-thermal stability and its poor mechanical properties limit this polymer use. The aim of this work is to obtain a modulation of the final scaffolds characteristics such as fibers dimension, wettability, elasticity, and resistance to rupture through the choice of the polymers to be electrospun. Different electrospun scaffolds containing gelatin, Poly-DL-lactic acid, different percentages of cellulose nanocrystals and an elastin peptide have been produced. Thermal stability, physical structure, and its mechanical behavior have been studied. Results suggest that the electrospun scaffolds show better thermal and mechanical properties than bulk materials; that is, the scaffolds with the best hydrophilic and thermomechanical properties are the samples containing 3% (wt/wt) of CNCs and elastin peptide.     

Novel 3D scaffolds of chitosan–PLLA blends for tissue engineering applications: Preparation and characterization

This work addresses the preparation of 3D porous scaffolds of blends of chitosan and poly(l-lactic acid), CHT and PLLA, using supercritical fluid technology. Supercritical assisted phase-inversion was used to prepare scaffolds for tissue engineering purposes. The physicochemical and biological properties of chitosan make it an excellent material for the preparation of drug delivery systems and for the development of new biomedical applications in many fields from skin to bone or cartilage regeneration. On the other hand, PLLA is a synthetic biodegradable polymer widely used for biomedical applications. Supercritical assisted phase-inversion experiments were carried out in samples with different polymer ratios and different polymer solution concentrations. The effect of CHT:PLLA ratio and polymer concentration and on the morphology and topography of the scaffolds was assessed by SEM and Micro-CT. Infra-red spectroscopic imaging analysis of the scaffolds allowed a better understanding on the distribution of the two polymers within the matrix. This work demonstrates that supercritical fluid technology constitutes a new processing technology, clean and environmentally friendly for the preparation of scaffolds for tissue engineering using these materials.     

Preparation and application of chitin and its derivatives: a review

Chitin the second most abundant polysaccharide is synthesized by an enormous number of living organisms including fungi and insects. These biopolymers have found many applications in different areas such as: packaging material, membrane for removal of metal ions, dyes and pigments in waste water engineering; anti-cholesterol, fat binding, preservative and food additive in food industry; seed and fertilizer coating, controlled agrochemical release in agriculture; surface treatment, photographic paper in pulp and paper industry; moisturizer, body creams and lotions in cosmetics and toiletries. It has also found wide applications in biomedical such as tissue engineering, drug delivery, wound dressing, scaffolds, cancer diagnosis, etc. The majority of these versatile applications are coming of its non-toxicity, biocompatibility and biodegradability. Chitin is also easily processed as gel, membrane, and nanofiber. This review emphasizes an extensive bibliography of recent basic and applied research and investigations on the aspects of this interesting biopolymer including the recovery, preparation, modification and application of chitin and its derivatives and related compounds. A new class of biocompatible and biodegradable chitin-based polyurethane (PU) elastomer was also introduced and reviewed in this study and it was found that by incorporation of chitin into the PU elastomer backbone, biocompatibility and degradation rate of the final elastomer improved. PUs are one of the synthetic biocompatible polymers with excellent physical and mechanical properties. Combination of this polymer with chitin resulted to a new tailor-made biocompatible and biodegradable polymer with improved properties. These polymers have potential applications in various applications including biomedical.     

Alginate: properties and biomedical applications

Alginate is a biomaterial that has found numerous applications in biomedical science and engineering due to its favorable properties, including biocompatibility and ease of gelation. Alginate hydrogels have been particularly attractive in wound healing, drug delivery, and tissue engineering applications to date, as these gels retain structural similarity to the extracellular matrices in tissues and can be manipulated to play several critical roles. This review will provide a comprehensive overview of general properties of alginate and its hydrogels, their biomedical applications, and suggest new perspectives for future studies with these polymers.     

Porous Chitosan Scaffolds: A Systematic Study for Choice of Crosslinker and Growth Factor Incorporation

A systematic study was conducted to evaluate the crosslinker and method of incorporation for bovine serum albumin (BSA) into chitosan hybrid scaffolds (CH-ALG) for better cartilage tissue engineering applications. Formaldehyde and sodium tripolyphosphate were used crosslinkers for fabrication of CH-ALG scaffolds using BSA as growth factor by direct incorporation and microencapsulation methods. An in vitro release study of BSA with maximum release (80%) for scaffolds of formaldehyde crosslinked was found. The present findings show that the CH-ALG hybrid scaffolds have been potential use in biomedical applications.     

The Marine Polysaccharide Ulvan Confers Potent Osteoinductive Capacity to PCL-Based Scaffolds for Bone Tissue Engineering Applications

Hybrid composites of synthetic and natural polymers represent materials of choice for bone tissue engineering. Ulvan, a biologically active marine sulfated polysaccharide, is attracting great interest in the development of novel biomedical scaffolds due to recent reports on its osteoinductive properties. Herein, a series of hybrid polycaprolactone scaffolds containing ulvan either alone or in blends with κ-carrageenan and chondroitin sulfate was prepared and characterized. The impact of the preparation methodology and the polysaccharide composition on their morphology, as well as on their mechanical, thermal, water uptake and porosity properties was determined, while their osteoinductive potential was investigated through the evaluation of cell adhesion, viability, and osteogenic differentiation of seeded human adipose-derived mesenchymal stem cells. The results verified the osteoinductive ability of ulvan, showing that its incorporation into the polycaprolactone matrix efficiently promoted cell attachment and viability, thus confirming its potential in the development of biomedical scaffolds for bone tissue regeneration applications.     

Functionalized nanostructures with application in regenerative medicine

In the last decade, both regenerative medicine and nanotechnology have been broadly developed leading important advances in biomedical research as well as in clinical practice. The manipulation on the molecular level and the use of several functionalized nanoscaled materials has application in various fields of regenerative medicine including tissue engineering, cell therapy, diagnosis and drug and gene delivery. The themes covered in this review include nanoparticle systems for tracking transplanted stem cells, self-assembling peptides, nanoparticles for gene delivery into stem cells and biomimetic scaffolds useful for 2D and 3D tissue cell cultures, transplantation and clinical application.     

A Review of the Use of Microparticles for Cartilage Tissue Engineering

Tissue and organ failure has induced immense economic and healthcare concerns across the world. Tissue engineering is an interdisciplinary biomedical approach which aims to address the issues intrinsic to organ donation by providing an alternative strategy to tissue and organ transplantation. This review is specifically focused on cartilage tissue. Cartilage defects cannot readily regenerate, and thus research into tissue engineering approaches is relevant as a potential treatment option. Cells, scaffolds, and growth factors are three components that can be utilized to regenerate new tissue, and in particular recent advances in microparticle technology have excellent potential to revolutionize cartilage tissue regeneration. First, microspheres can be used for drug delivery by injecting them into the cartilage tissue or joint space to reduce pain and stimulate regeneration. They can also be used as controlled release systems within tissue engineering constructs. Additionally, microcarriers can act as a surface for stem cells or chondrocytes to adhere to and expand, generating large amounts of cells, which are necessary for clinically relevant cell therapies. Finally, a newer application of microparticles is to form them together into granular hydrogels to act as scaffolds for tissue engineering or to use in bioprinting. Tissue engineering has the potential to revolutionize the space of cartilage regeneration, but additional research is needed to allow for clinical translation. Microparticles are a key enabling technology in this regard.     

Chitosan: Application in tissue engineering and skin grafting

Tissue Engineering and skin grafting, an essential part of regenerative medicine is one of the fastest growing biomedical fields which could offer an important therapeutic strategy for management of hard to heal wounds. 2D and 3D polymeric scaffolds are prerequisites in this field to promote cell adhesion, proliferation and tissue regeneration. Convergence of technology and research has successfully unveiled unknown properties of Chitosan as a bioactive polymer. Natural abundance, cost effectiveness, biodegradability, biocompatibility and wound healing capabilities of chitosan and its derivatives has drawn the attention of many researchers for its use as an alternative for fabrication of a scaffold in tissue engineering and skin graft. However lower mechanical strength and solubility has limited its application in the biomedical field. It has been found that the derivatization and combination with other polymers can successfully overcome these limitations. This review focuses on the applicability of chitosan and its derivatives in combination with other polymers in tissue engineering and skin grafting along with the novel scaffold fabrication techniques. Studies so far have demonstrated the potential of chitosan and its derivative as a scaffold in the field of regenerative medicine. However, even if the promising results obtained from in-vitro and preclinical studies prove the efficacy of chitosan scaffolds it still has a long way to go to be used in clinical set ups.     

Application Progress of Modified Chitosan and Its Composite Biomaterials for Bone Tissue Engineering

In recent years, bone tissue engineering (BTE), as a multidisciplinary field, has shown considerable promise in replacing traditional treatment modalities (i.e., autografts, allografts, and xenografts). Since bone is such a complex and dynamic structure, the construction of bone tissue composite materials has become an attractive strategy to guide bone growth and regeneration. Chitosan and its derivatives have been promising vehicles for BTE owing to their unique physical and chemical properties. With intrinsic physicochemical characteristics and closeness to the extracellular matrix of bones, chitosan-based composite scaffolds have been proved to be a promising candidate for providing successful bone regeneration and defect repair capacity. Advances in chitosan-based scaffolds for BTE have produced efficient and efficacious bio-properties via material structural design and different modifications. Efforts have been put into the modification of chitosan to overcome its limitations, including insolubility in water, faster depolymerization in the body, and blood incompatibility. Herein, we discuss the various modification methods of chitosan that expand its fields of application, which would pave the way for future applied research in biomedical innovation and regenerative medicine.     

Nanoscale Bioactive Glasses in Medical Applications

This review focuses on recent advances in the development and use of nanoscale silicate bioactive glasses for medical applications. In the context of materials for bone substitution, dental applications, and bone tissue engineering, nanoscale bioactive glasses have been gaining attention due to their expected superior osteoconductivity when compared with conventional (micrometer-sized) bioactive glass materials. A detailed overview of recent developments in the field of nanoscale bioactive glasses will be given, including a summary of common fabrication methods and diverse application areas which include tissue engineering scaffolds and coatings, drug delivery devices, and dentistry. The nanofeatures characteristic of this type of bioactive glasses and the possibilities to expand their use in biomedical applications (nanomedicine) are highlighted.     

Natural and Genetically Engineered Proteins for Tissue Engineering

To overcome the limitations of traditionally used autografts, allografts and, to a lesser extent, synthetic materials, there is the need to develop a new generation of scaffolds with adequate mechanical and structural support, control of cell attachment, migration, proliferation and differentiation and with bio-resorbable features. This suite of properties would allow the body to heal itself at the same rate as implant degradation. Genetic engineering offers a route to this level of control of biomaterial systems. The possibility of expressing biological components in nature and to modify or bioengineer them further, offers a path towards multifunctional biomaterial systems. This includes opportunities to generate new protein sequences, new self-assembling peptides or fusions of different bioactive domains or protein motifs. New protein sequences with tunable properties can be generated that can be used as new biomaterials.In this review we address some of the most frequently used proteins for tissue engineering and biomedical applications and describe the techniques most commonly used to functionalize protein-based biomaterials by combining them with bioactive molecules to enhance biological performance. We also highlight the use of genetic engineering, for protein heterologous expression and the synthesis of new protein-based biopolymers, focusing the advantages of these functionalized biopolymers when compared with their counterparts extracted directly from nature and modified by techniques such as physical adsorption or chemical modification.