Graphene: a versatile nanoplatform for biomedical applications

Graphene, with its excellent physical, chemical, and mechanical properties, holds tremendous potential for a wide variety of biomedical applications. As research on graphene-based nanomaterials is still at a nascent stage due to the short time span since its initial report in 2004, a focused review on this topic is timely and necessary. In this feature review, we first summarize the results from toxicity studies of graphene and its derivatives. Although literature reports have mixed findings, we emphasize that the key question is not how toxic graphene itself is, but how to modify and functionalize it and its derivatives so that they do not exhibit acute/chronic toxicity, can be cleared from the body over time, and thereby can be best used for biomedical applications. We then discuss in detail the exploration of graphene-based nanomaterials for tissue engineering, molecular imaging, and drug/gene delivery applications. The future of graphene-based nanomaterials in biomedicine looks brighter than ever, and it is expected that they will find a wide range of biomedical applications with future research effort and interdisciplinary collaboration.     

Polymeric nanostructured materials for biomedical applications

Polymeric nanostructured materials (PNMs), which are polymeric materials in nanoscale or polymer composites containing nanomaterials, have become increasingly useful for biomedical applications. In specific, advances in polymer-related nanoscience and nanotechnology have brought a revolutionary change to produce new biomaterials with tailored properties and functionalities for targeted biomedical applications. These materials, including micelles, polymersomes, nanoparticles, nanocapsules, nanogels, nanofibers, dendrimers and nanocomposites, have been widely used in drug delivery, gene therapy, bioimage, tissue engineering and regenerative medicine. This review presents a comprehensive overview on the various types of PNMs, their fabrication methods and biomedical applications, as well as the challenges in research and development of future PNMs.     

Emerging Perspectives in the Synthesis of Novel Degradable Biomedical Copolymers

Biodegradable polymer is playing an increasingly significant role in the development of biomedical materials due to its good biocompatibility and biodegradability, and is undoubtedly the focus in the biomedical fields, such as controlled drug delivery, tissue engineering, and regenerative medicine. In this review, some new degradable biomedical copolymers reported over the past 5 years are introduced and discussed in combination with some our research results. The molecular design, chemical structures and related properties of these novel biodegradable copolymers are reported. In summarizing the review, the development, potential applications and future directions of the degradable biomedical copolymers are discussed.     

Advanced graphene ceramics and their future in bone regenerative engineering

The outstanding properties of graphene materials rely on an exceptional two-dimensional honeycombed lattice. The lattice allows for electrical, thermal, and mechanical reinforcement effects when applied to the ceramic matrix. The biocompatibility of the material allows for providing multifunctional bioceramics applications. However, the potential of graphene lies in its ability to be homogenously distributed as part of a ceramic matrix. Therefore, appropriate processing techniques are important for attaining desired graphene ceramic properties applicable for regenerative biomedical purposes. This article provides an inclusive review of the current knowledge of advanced graphene-based ceramics for bone regenerative engineering. In this review, the opportunities and challenges in utilizing graphene materials in combination with ceramics suitable for applications in load-bearing bone defects are discussed.     

Poly-3-hydroxybutyrate-based constructs with novel characteristics for drug delivery and tissue engineering applications—A review

Herein, we reviewed polymeric constructs of polyhydroxyalkanoates (PHAs) at large and poly-3-hydroxybutyrate (P3HB), in particular, for drug delivery and tissue engineering applications. Polymeric constructs that can efficiently respond to numerous variations in their surroundings have gained notable attention from different industrial sectors such as biomedical, clinical, pharmaceutical, and cosmeceutical. Among them, considerable importance is given to their drug delivery and tissue engineering applications. PHAs with peculiar reference to P3HB are gaining prominence attention as candidate materials with such requisite potentialities. The unique structural and functional characteristics of PHAs and P3HB are of supreme interest and being used to engineer novel constructs for efficient drug delivery and tissue regeneration purposes. So far, an array of methodological approaches, such as in vitro, in vivo, and ex vivo techniques have been exploited though using different materials with different geometries for a said purpose. However, a low-level production majorly limits their proper exploitation. Various physiochemical characteristics and production strategies have been introduced in this review. The data have been summarized on PHAs production by several microorganisms aiming to cover the scope of the last 10 years. The present review highlights the recent applications of PHAs and P3HB-based constructs, such as micro/nanoparticles, biocomposite, nanofibers, and hydrogels as novel drug carries for regenerative medicine and tissue engineering. In summary, drug delivery and tissue engineering potentialities of PHAs and P3HB-based constructs are discussed with suitable examples and envisioned directions of future developments.     

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.     

Chitin scaffolds in tissue engineering

Tissue engineering/regeneration is based on the hypothesis that healthy stem/progenitor cells either recruited or delivered to an injured site, can eventually regenerate lost or damaged tissue. Most of the researchers working in tissue engineering and regenerative technology attempt to create tissue replacements by culturing cells onto synthetic porous three-dimensional polymeric scaffolds, which is currently regarded as an ideal approach to enhance functional tissue regeneration by creating and maintaining channels that facilitate progenitor cell migration, proliferation and differentiation. The requirements that must be satisfied by such scaffolds include providing a space with the proper size, shape and porosity for tissue development and permitting cells from the surrounding tissue to migrate into the matrix. Recently, chitin scaffolds have been widely used in tissue engineering due to their non-toxic, biodegradable and biocompatible nature. The advantage of chitin as a tissue engineering biomaterial lies in that it can be easily processed into gel and scaffold forms for a variety of biomedical applications. Moreover, chitin has been shown to enhance some biological activities such as immunological, antibacterial, drug delivery and have been shown to promote better healing at a faster rate and exhibit greater compatibility with humans. This review provides an overview of the current status of tissue engineering/regenerative medicine research using chitin scaffolds for bone, cartilage and wound healing applications. We also outline the key challenges in this field and the most likely directions for future development and we hope that this review will be helpful to the researchers working in the field of tissue engineering and regenerative medicine.     

Advances in Biologically Applicable Graphene-Based 2D Nanomaterials

Climate change and increasing contamination of the environment, due to anthropogenic activities, are accompanied with a growing negative impact on human life. Nowadays, humanity is threatened by the increasing incidence of difficult-to-treat cancer and various infectious diseases caused by resistant pathogens, but, on the other hand, ensuring sufficient safe food for balanced human nutrition is threatened by a growing infestation of agriculturally important plants, by various pathogens or by the deteriorating condition of agricultural land. One way to deal with all these undesirable facts is to try to develop technologies and sophisticated materials that could help overcome these negative effects/gloomy prospects. One possibility is to try to use nanotechnology and, within this broad field, to focus also on the study of two-dimensional carbon-based nanomaterials, which have excellent prospects to be used in various economic sectors. In this brief up-to-date overview, attention is paid to recent applications of graphene-based nanomaterials, i.e., graphene, graphene quantum dots, graphene oxide, graphene oxide quantum dots, and reduced graphene oxide. These materials and their various modifications and combinations with other compounds are discussed, regarding their biomedical and agro-ecological applications, i.e., as materials investigated for their antineoplastic and anti-invasive effects, for their effects against various plant pathogens, and as carriers of bioactive agents (drugs, pesticides, fertilizers) as well as materials suitable to be used in theranostics. The negative effects of graphene-based nanomaterials on living organisms, including their mode of action, are analyzed as well.     

Functionalization of polymer multilayer thin films for novel biomedical applications

The design of functional polymer multilayer thin films with nanometer scale control is of great interest for biomedical applications such as tissue engineering, targeted drug delivery, controlled release system, and regenerative medicine. Various functions and properties of polymer thin films can be easily programmed and realized by the layer-by-layer assembly strategy, which is a facile and versatile deposition method to prepare well-defined biomedical multilayer platforms due to its benign process to prepare films under mild conditions and the capability of incorporating bioactive materials at a desired location within the films. Particularly, the fine tuning of physicochemical and biological properties of multilayer thin films is significantly important for designing novel biomedical platforms capable of adjusting the cellular functions. In this review, we focus on the overall background of the layer-by-layer assembly as well as the tuning of multilayer film properties and the programming of biological functions into the polymer thin films with a view on the control of cellular functions. Furthermore, we highlighted the recent achievements toward the design of novel biomedical platforms based on functionalized polymer multilayer thin films.     

自组装肽基纳米材料运载药物和基因的研究进展

肽基分子自组装以其丰富的自组装驱动力、新颖的自组装体纳米结构、自组装体的特殊功能及良好的生物相容性等,在纳米生物材料、护肤和化妆产品、药物传输释放、组织工程支架材料等方面有着广泛的应用前景。由天然氨基酸组成的自组装短肽具有良好的低细胞毒性,可控的降解性能,高的运载效率及细胞摄取率,同时还具有降低药物的毒副作用等优点。因此,它在作为药物和基因的纳米载药材料方面有着巨大的发展前景。使用自组装肽基材料形成的纳米载体对疏水性抗癌药物、蛋白质药物及基因等进行传递释放已成为生物医药学领域的研究重点,因此,对近年来自组装肽基纳米材料作为药物和基因载体在生物医药学上的研究进展做了综述。     

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.     

ATRP in the design of functional materials for biomedical applications

Atom Transfer Radical Polymerization (ATRP) is an effective technique for the design and preparation of multifunctional, nanostructured materials for a variety of applications in biology and medicine. ATRP enables precise control over macromolecular structure, order, and functionality, which are important considerations for emerging biomedical designs. This article reviews recent advances in the preparation of polymer-based nanomaterials using ATRP, including polymer bioconjugates, block copolymer-based drug delivery systems, cross-linked microgels/nanogels, diagnostic and imaging platforms, tissue engineering hydrogels, and degradable polymers. It is envisioned that precise engineering at the molecular level will translate to tailored macroscopic physical properties, thus enabling control of the key elements for realized biomedical applications.     

Review of crosslinked and non‐crosslinked copolyesters for tissue engineering and drug delivery

Novel degradable biomedical materials are found to have huge potential applications in fields such as drug delivery and release, orthopedic fixation support and tissue engineering. Utilization of polymers as biomaterials has greatly impacted the advancement of modern medicine. In this review, some new degradable biomedical copolyesters reported in recent years are introduced and discussed in combination with some of our research results, including non‐crosslinked copolyesters, crosslinked copolyesters and their corresponding derivatives. The molecular design, chemical structures and related properties of these biodegradable copolyesters are reported. In summarizing the review, the development, potential applications and future directions of degradable biomedical copolyesters are discussed. © 2013 Society of Chemical Industry     

Application of polymeric nanofibers in medical designs,part I: Skin and eye

Nanotechnology has wide applications in many fields, especially in the biological sciences and medicine. Nanomaterials are applied as potential materials for treatment and diagnosis. The development of nanofibers has greatly enhanced the scope for fabricating designs that can be potentially used in medical sciences. The application of polymeric nanofibers in biomaterials sciences and tissue engineering review in four sections: skin and eye, neural and cardiovascular tissues, musculoskeletal and urological tissues, drug and biological materials’ delivery. The present review summarizes the currently available applications of nanofibers in skin and eye tissues.     

Chitosan—A versatile semi-synthetic polymer in biomedical applications

This review outlines the new developments on chitosan-based bioapplications. Over the last decade, functional biomaterials research has developed new drug delivery systems and improved scaffolds for regenerative medicine that is currently one of the most rapidly growing fields in the life sciences. The aim is to restore or replace damaged body parts or lost organs by transplanting supportive scaffolds with appropriate cells that in combination with biomolecules generate new tissue. This is a highly interdisciplinary field that encompasses polymer synthesis and modification, cell culturing, gene therapy, stem cell research, therapeutic cloning and tissue engineering. In this regard, chitosan, as a biopolymer derived macromolecular compound, has a major involvement. Chitosan is a polyelectrolyte with reactive functional groups, gel-forming capability, high adsorption capacity and biodegradability. In addition, it is innately biocompatible and non-toxic to living tissues as well as having antibacterial, antifungal and antitumor activity. These features highlight the suitability and extensive applications that chitosan has in medicine. Micro/nanoparticles and hydrogels are widely used in the design of chitosan-based therapeuticsystems. The chemical structure and relevant biological properties of chitosan for regenerative medicine have been summarized as well as the methods for the preparation of controlled drug release devices and their applications.     

Chemical Modifications of Chitosan and Its Applications

Chitosan is considered as a promising material in the pharmaceutical and biomedical fields based on its unique biological properties. This review presents chemical modifications of chitosan via using photosensitizers, dendrimers, sugars, cyclodextrins and crown ethers as modifiers and places an emphasis on the applications of chitosan derivatives as carriers in drug delivery systems, as supporting materials for tissue engineering, as dye removing agents and as metal ion adsorbents. Recently, the progress on chemical modifications of chitosan is quite rapid and we are confident that a more extensive range of applications of chitosan derivatives could be expected in the near future.     

胶原蛋白检测方法研究进展

胶原蛋白具有良好的理化性能和生物学特性,生物医学材料、药物输送载体、组织工程、化妆品和食品等领域有着广泛的应用。因此,胶原蛋白种类的鉴别和含量的测定变得越来越重要。本文对胶原蛋白的鉴别及其含量的检测方法做了详细的介绍,并对其检测方法的发展前景进行了展望。     

Development of 3D in Vitro Technology for Medical Applications

In the past few years, biomaterials technologies together with significant efforts on developing biology have revolutionized the process of engineered materials. Three dimensional (3D) in vitro technology aims to develop set of tools that are simple, inexpensive, portable and robust that could be commercialized and used in various fields of biomedical sciences such as drug discovery, diagnostic tools, and therapeutic approaches in regenerative medicine. The proliferation of cells in the 3D scaffold needs an oxygen and nutrition supply. 3D scaffold materials should provide such an environment for cells living in close proximity. 3D scaffolds that are able to regenerate or restore tissue and/or organs have begun to revolutionize medicine and biomedical science. Scaffolds have been used to support and promote the regeneration of tissues. Different processing techniques have been developed to design and fabricate three dimensional scaffolds for tissue engineering implants. Throughout the chapters we discuss in this review, we inform the reader about the potential applications of different 3D in vitro systems that can be applied for fabricating a wider range of novel biomaterials for use in tissue engineering.     

Polyphosphazenes—A Promising Candidate for Drug Delivery,Bioimaging, and Tissue Engineering: A Review

Synthetic polymer materials have been surged to the forefront of research in the fields of tissue engineering, drug delivery, and biomonitoring in recent years. Biodegradable synthetic polymers are increasingly needed as transient substrates for tissue regeneration and medicine delivery. In contrast to commonly used polymers including polyesters, polylactones, polyanhydrides, poly(propylene fumarates), polyorthoesters, and polyurethanes, biodegradable polyphosphazenes (PPZs) hold great potential for the purposes indicated above. PPZ's versatility in the synthetic process has enabled the production of a variety of polymers with various physico-chemical, and biological properties have been produced, making them appropriate for biomedical applications. Biocompatible PPZs are often used as scaffolds in the regeneration of skeleton, bones, and other tissues. PPZs have also received special attention as potential drug vehicles of high-value biopharmaceuticals such as anticancer drugs. Additionally, by incorporating fluorophores into the PPZ backbone to produce photoluminescent biodegradable PPZs, the utility of polyphosphazenes is further expanded as they are used in tracking the regeneration of the target tissue as well as the fate of PPZ based scaffolds or drug delivery vehicles. This review provides a summary of the evolution of PPZ applications in the fields of tissue engineering, drug delivery, and bioimaging in recent 5 years.     

NVCL-Based Hydrogels and Composites for Biomedical Applications: Progress in the Last Ten Years

Hydrogels consist of three-dimensionally crosslinked polymeric chains, are hydrophilic, have the ability to absorb other molecules in their structure and are relatively easy to obtain. However, in order to improve some of their properties, usually mechanical, or to provide them with some physical, chemical or biological characteristics, hydrogels have been synthesized combined with other synthetic or natural polymers, filled with inorganic nanoparticles, metals, and even polymeric nanoparticles, giving rise to composite hydrogels. In general, different types of hydrogels have been synthesized; however, in this review, we refer to those obtained from the thermosensitive polymer poly(N-vinylcaprolactam) (PNVCL) and we focus on the definition, properties, synthesis techniques, nanomaterials used as fillers in composites and mainly applications of PNVCL-based hydrogels in the biomedical area. This type of material has great potential in biomedical applications such as drug delivery systems, tissue engineering, as antimicrobials and in diagnostic and bioimaging.