Showing papers in "Biomaterials Science in 2017"

Keratin: dissolution, extraction and biomedical application

Abstract: Keratinous materials such as wool, feathers and hooves are tough unique biological co-products that usually have high sulfur and protein contents A high cystine content (7–13%) differentiates keratins from other structural proteins, such as collagen and elastin Dissolution and extraction of keratin is a difficult process compared to other natural polymers, such as chitosan, starch, collagen, and a large-scale use of keratin depends on employing a relatively fast, cost-effective and time efficient extraction method Keratin has some inherent ability to facilitate cell adhesion, proliferation, and regeneration of the tissue, therefore keratin biomaterials can provide a biocompatible matrix for regrowth and regeneration of the defective tissue Additionally, due to its amino acid constituents, keratin can be tailored and finely tuned to meet the exact requirement of degradation, drug release or incorporation of different hydrophobic or hydrophilic tails This review discusses the various methods available for the dissolution and extraction of keratin with emphasis on their advantages and limitations The impacts of various methods and chemicals used on the structure and the properties of keratin are discussed with the aim of highlighting options available toward commercial keratin production This review also reports the properties of various keratin-based biomaterials and critically examines how these materials are influenced by the keratin extraction procedure, discussing the features that make them effective as biomedical applications, as well as some of the mechanisms of action and physiological roles of keratin Particular attention is given to the practical application of keratin biomaterials, namely addressing the advantages and limitations on the use of keratin films, 3D composite scaffolds and keratin hydrogels for tissue engineering, wound healing, hemostatic and controlled drug release

Manipulating tumor hypoxia toward enhanced photodynamic therapy (PDT)

Abstract: Photodynamic therapy (PDT) is considered a promising approach for the treatment of cancer and is achieved via the photosensitizer (PS)-mediated incomplete reduction of oxygen upon light irradiation, which generates high levels of reactive oxygen species (ROS) to induce potent vascular damage and to directly kill tumor cells. However, there is an undesirable impediment with this approach in that tumor tissues generally suffer from serious hypoxia, which significantly affects the efficiency of PDT. Additionally, PDT that consumes oxygen will further aggravate tumor hypoxia, thus potentially leading to multiple undesirable consequences, such as angiogenesis, tumor invasiveness, and tumor metastasis. This mini-review provides a comprehensive overview of the recent research progress on overcoming or utilizing tumor hypoxia to enhance the therapeutic efficacy of PDT.

Synthesis, properties and biomedical applications of hydrolytically degradable materials based on aliphatic polyesters and polycarbonates

Abstract: Polyester-based polymers represent excellent candidates in synthetic biodegradable and bioabsorbable materials for medical applications owing to their tailorable properties. The use of synthetic polyesters as biomaterials offers a unique control of morphology, mechanical properties and degradation profile through monomer selection, polymer composition (i.e. copolymer vs. homopolymer, stereocomplexation etc.) and molecular weight. Within this review, the synthetic routes, degradation modes and application of aliphatic polyester- and polycarbonate-based biomaterials are discussed.

Personalized protein corona on nanoparticles and its clinical implications

Abstract: It is now well understood that once in contact with biological fluids, nanoscale objects lose their original identity and acquire a new biological character, referred to as a protein corona. The protein corona changes many of the physicochemical properties of nanoparticles, including size, surface charge, and aggregation state. These changes, in turn, affect the biological fate of nanoparticles, including their pharmacokinetics, biodistribution, and therapeutic efficacy. It is progressively being accepted that even slight variations in the composition of a protein source (e.g., plasma and serum) can substantially change the composition of the corona formed on the surface of the exact same nanoparticles. Recently it has been shown that the protein corona is strongly affected by the patient's specific disease. Therefore, the same nanomaterial incubated with plasma proteins of patients with different pathologies adsorb protein coronas with different compositions, giving rise to the concept of personalized protein corona. Herein, we review this concept along with recent advances on the topic, with a particular focus on clinical relevance.

Viscoelastic hydrogels for 3D cell culture.

Abstract: In tissues, many cells are surrounded by and interact with a three-dimensional soft extracellular matrix (ECM). Both the physical and biochemical properties of the ECM play a major role in regulating cell behaviours. To better understand the impact of ECM properties on cell behaviours, natural and synthetic hydrogels have been developed for use as synthetic ECMs for 3D cell culture. It has long been known that ECM and tissues are viscoelastic, or display a time-dependent response to deformation or mechanical loading, exhibiting stress relaxation and creep. However, only recently have there been efforts made to understand the role of the time-dependent aspects of the ECM mechanics on regulating cell behaviours using hydrogels for 3D culture. Here we review the characterization and molecular basis of hydrogel viscoelasticity and plasticity, and describe newly developed approaches to tuning viscoelasticity in hydrogels for 2D and 3D culture. Then we highlight several recent studies finding a potent impact of hydrogel stress relaxation or creep on cell behaviours such as cell spreading, proliferation, and differentiation of mesenchymal stem cells. The role of time-dependent mechanics on cell biology remains largely unclear, and ripe for further exploration. Further elucidation of this topic may substantially advance our understanding of cell–matrix interactions during development, homeostasis, wound healing, and disease, and guide the design of biomaterials for regenerative medicine.

Recent progress in the biomedical applications of polydopamine nanostructures

Abstract: Polydopamine is a dark brown-black insoluble biopolymer produced by autoxidation of dopamine Although its structure and polymerization mechanism have not been fully understood, there has been a rapid growth in the synthesis and applications of polydopamine nanostructures in biomedical fields such as drug delivery, photothermal therapy, bone and tissue engineering, and cell adhesion and patterning, as well as antimicrobial applications This article is dedicated to reviewing some of the recent polydopamine developments in these biomedical fields Firstly, the polymerization mechanism is introduced with a discussion of the factors that influence the polymerization process The discussion is followed by the introduction of various forms of polydopamine nanostructures and their recent applications in biomedical fields, especially in drug delivery Finally, the review is summarized followed by brief comments on the future prospects of polydopamine

3D printed porous ceramic scaffolds for bone tissue engineering: a review.

Abstract: This study summarizes the recent research status and development of three-dimensional (3D)-printed porous ceramic scaffolds in bone tissue engineering. Recent literature on 3D-printed porous ceramic scaffolds was reviewed. Compared with traditional processing and manufacturing technologies, 3D-printed porous ceramic scaffolds have obvious advantages, such as enhancement of the controllability of the structure or improvement of the production efficiency. More sophisticated scaffolds were fabricated by 3D printing technology. 3D printed bioceramics have broad application prospects in bone tissue engineering. Through understanding the advantages and limitations of different 3D-printing approaches, new classes of bone graft substitutes can be developed.

In vitro and in vivo analysis of visible light crosslinkable gelatin methacryloyl (GelMA) hydrogels

Abstract: Photocrosslinkable materials have been frequently used for constructing soft and biomimetic hydrogels for tissue engineering. Although ultraviolet (UV) light is commonly used for photocrosslinking such materials, its use has been associated with several biosafety concerns such as DNA damage, accelerated aging of tissues, and cancer. Here we report an injectable visible light crosslinked gelatin-based hydrogel for myocardium regeneration. Mechanical characterization revealed that the compressive moduli of the engineered hydrogels could be tuned in the range of 5–56 kPa by changing the concentrations of the initiator, co-initiator and co-monomer in the precursor formulation. In addition, the average pore sizes (26–103 μm) and swelling ratios (7–13%) were also shown to be tunable by varying the hydrogel formulation. In vitro studies showed that visible light crosslinked GelMA hydrogels supported the growth and function of primary cardiomyocytes (CMs). In addition, the engineered materials were shown to be biocompatible in vivo, and could be successfully delivered to the heart after myocardial infarction in an animal model to promote tissue healing. The developed visible light crosslinked hydrogel could be used for the repair of various soft tissues such as the myocardium and for the treatment of cardiovascular diseases with enhanced therapeutic functionality.

Microvalve-based bioprinting – process, bio-inks and applications

Abstract: Bioprinting is an emerging research field that has attracted tremendous attention for various applications; it offers a highly automated, advanced manufacturing platform for the fabrication of complex bioengineered constructs. Different bio-inks comprising multiple types of printable biomaterials and cells are utilized during the bioprinting process to improve the homology to native tissues and/or organs in a highly reproducible manner. This paper, presenting a first-time comprehensive yet succinct review of microvalve-based bioprinting, provides an in-depth analysis and comparison of different drop-on-demand bioprinting systems and highlights the important considerations for microvalve-based bioprinting systems. This review paper reports a detailed analysis of its printing process, bio-ink properties and cellular components on the printing outcomes. Lastly, this review highlights the significance of drop-on-demand bioprinting for various applications such as high-throughput screening, fundamental cell biology research, in situ bioprinting and fabrication of in vitro tissue constructs and also presents future directions to transform the microvalve-based bioprinting technology into imperative tools for tissue engineering and regenerative medicine.

Recent advances in carbon based nanosystems for cancer theranostics.

Abstract: One of the major challenges in our contemporary society is to facilitate healthy life for all human beings. In this context, cancer has become one of the most deadly diseases around the world, and despite many advances in theranostics techniques the treatment of cancer still remains an important problem. With recent advances made in the field of nano-biotechnology, carbon-based nanostructured materials have drawn special attention because of their unique physicochemical properties, giving rise to great potential for the diagnosis and therapy of cancer. This review deals with four different types of carbon allotrope including carbon nanotubes, graphene, fullerenes and nanodiamonds and summarizes the results of recent studies that are likely to have implications in cancer theranostics. We discuss the applications of these carbon allotropes for cancer imaging and drug delivery, hyperthermia, photodynamic therapy and acoustic wave assisted theranostics. We focus on the results of different studies conducted on functionalized/conjugated carbon nanotubes, graphene, fullerenes and nanodiamond based nanostructured materials reported in the literature in the current decade. The emphasis has been placed on the synthesis strategies, structural design, properties and possible mechanisms that are perhaps responsible for their improved theranostic characteristics. Finally, we discuss the critical issues that may accelerate the development of carbon-based nanostructured materials for application in cancer theranostics.

Noninvasive photothermal cancer therapy nanoplatforms via integrating nanomaterials and functional polymers

Abstract: In the cutting-edge field of cancer therapy, noninvasive photothermal therapy (PTT) has received great attention because it is considered to overcome the drawbacks of conventional surgery, radiotherapy and chemotherapy of severe body injuries and side effects on the immune system. The construction of PTT therapeutic and theranostic nanoplatforms is the key issue in achieving tumor targeting, imaging and therapy in a synergetic manner. In this review, we focus on the recent advances in constructing PTT therapeutic and theranostic nanoplatforms by integrating nanomaterials and functional polymers. The noninvasive photothermal cancer therapy mechanism and achievement strategies of PTT therapeutic and theranostic nanoplatforms are presented as well as the innovative construction strategies and perspectives for the future. Owing to their high tumor ablation efficiency, biological availability and low- or non-toxicity, PTT therapeutic and theranostic nanoplatforms are promising and emerging in medicine and clinical applications.

Design and development of polysaccharide hemostatic materials and their hemostatic mechanism.

Abstract: The formation of stable blood clots or hemostasis is essential to prevent major blood loss and death from excessive bleeding. However, the body's own coagulation process is not able to accomplish timely hemostasis without the assistance of hemostatic agents. For developing novel topical hemostatic agents, tissue adhesives and sealants, it is necessary to understand the coagulation process and the hemostasis mechanism of different materials. Among hemostatic materials, polysaccharides are naturally derived polymers having excellent biodegradable and biocompatible properties. This review provides an overview of polysaccharide-based hemostatic materials and agents, including their advantages and drawbacks in hemostatic applications. Furthermore, polysaccharide-based hemostatic materials with anti-microbial and healing functions are also introduced.

Peptide-functionalized gold nanoparticles: versatile biomaterials for diagnostic and therapeutic applications

Abstract: Colloidal gold solutions have been used for centuries in a wide variety of applications including staining glass and in the colouring of ceramics. More recently, gold nanoparticles (GNPs) have been studied extensively due to their interesting size-dependent electronic and optical properties. GNPs can be functionalized easily with biomolecules that contain thiols, amines, or even phosphine moieties. For example, the reaction of thiol-containing peptides with GNPs has been used extensively to prepare novel hybrid materials for biomedical applications. A range of different types of peptides can be used to access biomaterials that are designed to perform a specific role such as cancer cell targeting. In addition, specific peptide sequences that are responsive to external stimuli (e.g. temperature or pH) can be used to stabilise/destabilise the aggregation of colloidal GNPs. Such systems have exciting potential applications in the field of colorimetric sensing (including bio-sensing) and in targeted drug delivery platforms. In this review, we will give an overview of the current methods used for preparing peptide functionalized GNPs, and we will discuss their key properties outlining the various applications of this class of biomaterial. In particular, the potential applications of peptide functionalized GNPs in areas of sensing and targeted drug delivery will be discussed.

Surface modification and endothelialization of polyurethane for vascular tissue engineering applications: a review

Abstract: Cardiovascular implants, especially vascular grafts made of synthetic polymers, find wide clinical applications in the treatment of cardiovascular diseases. However, cases of failure still exist, notably caused by restenosis and thrombus formation. Aiming to solve these problems, various approaches to surface modification of synthetic vascular grafts have been used to improve both the hemocompatibility and long-term patency of artificial vascular grafts. Surface modification using hydrophilic molecules can enhance hemocompatibility, but this may limit the initial vascular endothelial cell adhesion. Therefore, the improvement of endothelialization on these grafts with specific peptides and biomolecules is now an exciting field of research. In this review, several techniques to improve surface modification and endothelialization on vascular grafts, mainly polyurethane (PU) grafts, are summarized, together with the recent development and evolution of the different strategies: from the use of PEG, zwitterions, and polysaccharides to peptides and other biomolecules and genes; from in vitro endothelialization to in vivo endothelialization; and from bio-inert and bio-active to bio-mimetic approaches.

Chemo-photodynamic combined gene therapy and dual-modal cancer imaging achieved by pH-responsive alginate/chitosan multilayer-modified magnetic mesoporous silica nanocomposites.

Abstract: Multifunctional theranostics have offered some interesting new opportunities for cancer therapy and diagnosis in the last decade. Herein, magnetic mesoporous silica nanoparticles (M-MSNs) were designed and synthesized, then the photosensitizer chlorin e6 (Ce6) and antitumor drug doxorubicin (Dox) were adsorbed onto the M-MSNs. Biocompatible alginate/chitosan polyelectrolyte multilayers (PEM) were assembled on the M-MSNs to achieve a pH-responsive drug delivery system and adsorb P-gp shRNA for reversing the multidrug resistance. The obtained M-MSN(Dox/Ce6)/PEM/P-gp shRNA nanocomposites were characterized using TEM, SEM, X-ray diffraction, BET, FTIR and electrophoresis. The nanocomposites with average diameter of 280 nm exhibited a pH-responsive drug release profile, and more singlet oxygen generation in cancer cells after laser illumination. CCK-8 assay and calcein-AM/PI co-staining showed that the multifunctional nanocomplexes significantly increased cell apoptosis in vitro. With tumor-bearing Balb/c mice employed as the animal model, combined photodynamic therapy and chemotherapy was carried out, also achieving synergistic anti-tumor effects in vivo. The cores of bifunctional Fe3O4-Au nanoparticles in the multifunctional nanocomposites enabled dual-modal MR and CT imaging, which illustrated strong tumor uptake of these nanocomposites after intravenous injection into tumor-bearing mice. This work highlights the great potential of magnetic mesoporous silica nanocomposites as a multifunctional delivery platform, which is promising for imaging-guided cancer combination therapy with high efficacy.

The scaffold microenvironment for stem cell based bone tissue engineering

Abstract: Bone tissue engineering uses the principles and methods of engineering and life sciences to study bone structure, function and growth mechanism for the purposes of repairing, maintaining and improving damaged bone tissue. Scaffolds not only provide structural support for stem cells in cell adhesion and proliferation and bone formation, but also serve as a microenvironment for guiding stem cell differentiation and tissue regeneration and for controlling tissue structure. This review presents the research status of the scaffold microenvironment for bone-related stem cells based on bone tissue engineering. Scaffold materials and the stem cell microenvironment are described in this review, and the existing shortcomings are also simply mentioned.

Therapeutic applications of iron oxide based nanoparticles in cancer: basic concepts and recent advances.

Abstract: Nanotechnology has introduced new techniques and phototherapy approaches to fabricate and utilize nanoparticles for cancer therapy. These phototherapy approaches, such as photothermal therapy (PTT) and photodynamic therapy (PDT), hold great promise to overcome the limitations of traditional treatment methods. In phototherapy, magnetic iron oxide nanoparticles (IONPs) are of paramount importance due to their wide range of biomedical applications. This review discusses the basic concepts, various therapy approaches (PTT, PDT, magnetic hyperthermia therapy (MHT), chemotherapy and immunotherapy), intrinsic properties, and mechanisms of cell death of IONPs; it also provides a brief overview of recent developments in IONPs, with focus on their therapeutic applications. Much attention is devoted to elaborating the various parameters, intracellular behaviors and limitations of MHT. Bimodal therapies which act alone or in combination with other modalities are also discussed. The review highlights some limitations in the explored research areas and suggests future directions to overcome these limitations.

Facile synthesis of black phosphorus-Au nanocomposites for enhanced photothermal cancer therapy and surface-enhanced Raman scattering analysis.

Abstract: Black phosphorus (BP), a new type of two-dimensional nanomaterial, has attracted crucial attention in recent years owing to its excellent properties and great potential in various chemical, physical, and biological fields. In this study, BP nanosheets loaded with Au nanoparticles (BP-Au NSs) are obtained by a one-step facile synthetic method. The Au nanostructures can not only enhance the photothermal efficiency of the nanocomposites, but also endow BP-Au NSs with the potential to act as effective surface-enhanced Raman scattering (SERS) substrates for Raman biodetection. Cancer photothermal therapy (PTT) has been carried out in vitro and in vivo using BP-Au NSs as nanoagents. Under irradiation by an 808 nm laser, BP-Au NSs are capable of producing sufficient hyperthermia to destroy cancer cells, and the transplanted tumors in most of the tumor-bearing mice disappeared; BP-Au NSs are more effective than bare BP nanosheets. The PTT effect can also be monitored by a Raman technique that benefits from the high SERS activity of the BP-Au NSs. The molecular fingerprint features of breast tumors before and after PTT treatment were clearly identified using SERS analysis. The theranostic applications of BP-Au NSs exhibit promising potential in biomedicine.

Yolk-structured multifunctional up-conversion nanoparticles for synergistic photodynamic-sonodynamic antibacterial resistance therapy

Abstract: The worldwide increase in bacterial antibiotic resistance has led to a search for alternative antibacterial therapies. The present study reports the development of yolk-structured multifunctional up-conversion nanoparticles (UCNPs) that combine photodynamic and sonodynamic therapy for effective killing of antibiotic-resistant bacteria. The multifunctional nanoparticles (NPs) were achieved by enclosing hematoporphyrin monomethyl ether (HMME) into its yolk-structured up-conversion core and covalently linked rose bengal (RB) on its silica (SiO2) shell. Excitation of UCNPs with near-infrared (NIR) light that has improved penetration depth for photodynamic therapy (PDT) enabled the activation of HMME and RB and thus the generation of singlet oxygen (1O2). The SiO2 layer, which improved the biocompatibility of the UCNPs, surrounded the yolk structure, with a cavity space which had a high efficiency of loading photosensitizers. Synergistic PDT and sonodynamic therapy (SDT) improved the photosensitizer utilization rate. As a result, a greater inhibition rate was observed when antibiotic-resistant bacteria were treated with a combined therapy (100%) compared with either the PDT (74.2%) or SDT (70%) alone. Our data indicate that the multifunctional NPs developed in this study have the potential for use in the clinical synergistic PDT-SDT treatment of infectious diseases caused by antibiotic-resistant bacteria.

Precision gas therapy using intelligent nanomedicine

Abstract: Gas therapy is an emerging and promising field, utilizing the unique therapeutic effects of several kinds of gases (NO, CO, H2S and H2) towards many major diseases, including cancer and cardiovascular diseases, and it is also facing challenges relating to enhancing gas therapy efficacy and avoiding gas poisoning risks. Here, we have proposed a new concept for precision gas therapy using a nanomedicine strategy to overcome the challenges. In this perspective, we have addressed a series of existing and potential solutions from the point of view of nanomedicine, and conveyed a collection of opinions about future expandable research into precision gas therapy.

Recent advances in nanomedicines for the treatment of rheumatoid arthritis

Abstract: Rheumatoid arthritis (RA) is a severe systemic inflammatory disease It is often associated with serious cartilage destruction and massive inflammatory infiltration, which might ultimately cause disability, wide complications and reduced life quality Current clinical treatments of RA show several drawbacks such as high doses, frequent administration and serious side effects These limitations have motivated tremendous expansion of the research and application of nanomedicines in RA therapy In this review, we summarize the cutting edge progress in nanomedicines for the treatment of RA and discuss the application of various targeting strategies Additionally, we also discuss the pivotal challenges to be addressed, as well as future perspectives

Carbon dots for tracking and promoting the osteogenic differentiation of mesenchymal stem cells

Abstract: Mesenchymal stem cells (MSCs) hold great potential for tissue engineering and regeneration medicine. However, for clinical use, MSCs may be detrimental due to their uncertain fate during the transplantation. It is therefore highly desirable to develop biocompatible nanomaterials to integrate cell fate regulation with monitoring for MSC-based therapy. Herein, we employ recently developed citric acid-based carbon dots (CDs) and their derivatives (Et-IPCA) for labeling and tracking of rat bone marrow mesenchymal stem cells (rBMSCs). We further investigate their biocompatibility and effects on the osteogenic differentiation of rBMSCs. These highly fluorescent probes provide labeling of rBMSCs by internalization without affecting cell viability or inducing apoptosis when the concentration is lower than 50 μg mL-1. Importantly, the presence of the CDs and Et-IPCA facilitates high-efficiency osteogenic differentiation of rBMSCs by promoting osteogenic transcription and enhancing matrix mineralization. Compared to Et-IPCA, CDs considerably provide long-term tracking and promote the differentiation of rBMSCs toward osteoblasts through the ROS-mediated MAPK pathway. Taken together, our results consistently demonstrate that carbon dots are capable of both tracking and enhancing the osteogenic differentiation of MSCs. This study sheds new light on the potential of carbon dots as a bifunctional tool in the thriving field of MSC-based therapy.

Molecular imprinting polymers and their composites: a promising material for diverse applications

Abstract: Molecular imprinted polymerization is considered one of the most useful preparation strategies to obtain highly selective polymeric materials called molecular imprinted polymers (MIPs). It has attracted a tremendous amount of interest in the last decade. Consequently, MIPs have been employed in a variety of applications including chromatographic separation, sensors and biosensors fabrication, drug delivery, proteomic analysis and plastic antibody synthesis, etc. The hybridization of the excellent features of MIPs and nanomaterials has further fueled the intensity of research in this area. A good number of works have been reported on MIP-nanomaterial composites in last few years covering all types of applications. In this review, we discuss the basic fundamentals of MIPs, nanomaterials and their combined applications. As a proof of concept, we included selective works published from 2012 to 2016.

Hydrogel based cartilaginous tissue regeneration: recent insights and technologies.

Abstract: Hydrogels have been extensively employed as an attractive biomaterial to address numerous existing challenges in the fields of regenerative medicine and research because of their unique properties such as the capability to encapsulate cells, high water content, ease of modification, low toxicity, injectability, in situ spatial fit and biocompatibility. These inherent properties have created many opportunities for hydrogels as a scaffold or a cell/drug carrier in tissue regeneration, especially in the field of cartilaginous tissue such as articular cartilage and intervertebral discs. A concise overview of the anatomy/physiology of these cartilaginous tissues and their pathophysiology, epidemiology and existing clinical treatments will be briefly described. This review article will discuss the current state-of-the-art of various polymers and developing strategies that are explored in establishing different technologies for cartilaginous tissue regeneration. In particular, an innovative approach to generate scaffold-free cartilaginous tissue via a transient hydrogel scaffolding system for disease modeling to pre-clinical trials will be examined. Following that, the article reviews numerous hydrogel-based medical implants used in clinical treatment of osteoarthritis and degenerated discs. Last but not least, the challenges and future directions of hydrogel based medical implants in the regeneration of cartilaginous tissue are also discussed.

Self-assembly of peptide amphiphiles for drug delivery: the role of peptide primary and secondary structures

Abstract: Peptide amphiphiles (PAs), functionalized with alkyl chains, are capable of self-assembling into various nanostructures Recently, PAs have been considered as ideal drug carriers due to their good biocompatibility, specific biological functions, and hypotoxicity to normal cells and tissues Meanwhile, the nanocarriers formed by PAs are able to achieve controlled drug release and enhanced cell uptake in response to the stimulus of the physiological environment or specific biological factors in the location of the lesion However, the underlying detailed drug delivery mechanism, especially from the aspect of primary and secondary structures of PAs, has not been systematically summarized or discussed Focusing on the relationship between the primary and secondary structures of PAs and stimuli-responsive drug delivery applications, this review highlights the recent advances, challenges, and opportunities of PA-based functional drug nanocarriers, and their potential pharmaceutical applications are discussed

Multifunctional PEI-entrapped gold nanoparticles enable efficient delivery of therapeutic siRNA into glioblastoma cells

Abstract: RNA interference (RNAi) has been considered as a promising strategy for effective treatment of cancer. However, the easy degradation of small interfering RNA (siRNA) limits its extensive applications in gene therapy. For safe and effective delivery of siRNA, a novel vector system possessing excellent biocompatibility, highly efficient transfection efficiency and specific targeting properties has to be considered. In this study, we report the use of polyethyleneimine (PEI)-entrapped gold nanoparticles (Au PENPs) modified with an arginine-glycine-aspartic (Arg-Gly-Asp, RGD) peptide via a poly(ethylene glycol) (PEG) spacer as a vector for Bcl-2 (B-cell lymphoma-2) siRNA delivery to glioblastoma cells. The synthesized Au PENPs were well characterized. The efficiency of siRNA delivery was appraised by flow cytometry, confocal microscopy imaging, and the protein expression level. Our results revealed that the Au PENPs were capable of delivering Bcl-2 siRNA to glioblastoma cells with an excellent transfection efficiency, leading to specific gene silencing in the target cells (22% and 25.5% Bcl-2 protein expression in vitro and in vivo, respectively) thanks to the RGD peptide-mediated targeting pathway. The designed RGD-targeted Au PENPs may hold great promise to be used as a novel vector for specific cancer gene therapy applications.

Neural stem cell proliferation and differentiation in the conductive PEDOT-HA/Cs/Gel scaffold for neural tissue engineering

Abstract: Engineering scaffolds with excellent electro-activity is increasingly important in tissue engineering and regenerative medicine. Herein, conductive poly(3,4-ethylenedioxythiophene) doped with hyaluronic acid (PEDOT-HA) nanoparticles were firstly synthesized via chemical oxidant polymerization. A three-dimensional (3D) PEDOT-HA/Cs/Gel scaffold was then developed by introducing PEDOT-HA nanoparticles into a chitosan/gelatin (Cs/Gel) matrix. HA, as a bridge, not only was used as a dopant, but also combined PEDOT into the Cs/Gel via chemical crosslinking. The PEDOT-HA/Cs/Gel scaffold was used as a conductive substrate for neural stem cell (NSC) culture in vitro. The results demonstrated that the PEDOT-HA/Cs/Gel scaffold had excellent biocompatibility for NSC proliferation and differentiation. 3D confocal fluorescence images showed cells attached on the channel surface of Cs/Gel and PEDOT-HA/Cs/Gel scaffolds with a normal neuronal morphology. Compared to the Cs/Gel scaffold, the PEDOT-HA/Cs/Gel scaffold not only promoted NSC proliferation with up-regulated expression of Ki67, but also enhanced NSC differentiation into neurons and astrocytes with up-regulated expression of β tubulin-III and GFAP, respectively. It is expected that this electro-active and bio-active PEDOT-HA/Cs/Gel scaffold will be used as a conductive platform to regulate NSC behavior for neural tissue engineering.

Nanocellulosic materials as bioinks for 3D bioprinting.

Abstract: 3D bioprinting is a new developing technology with lots of promise in tissue engineering and regenerative medicine. Being biocompatible, biodegradable, renewable and cost-effective, cellulosic nanomaterials have recently captured the attention of researchers due to their applicability as inks for 3D bioprinting. Although a number of cellulose-based bioinks have been reported, the potential of cellulose nanofibrils and nanocrystals has not been fully explored yet. This minireview aims at highlighting the use of nanocellulosic materials for 3D bioprinting as an emerging, promising, new research field.

Insight into the interactions between nanoparticles and cells.

Abstract: Multifunctional nanoparticles (NPs) have been widely used in biomedical applications because of their versatile properties. The properties of NPs should be well designed and controlled according to various applications because they may directly affect the functions and performances of NPs in biological systems. Cellular uptake is a prerequisite for the success of NP-based biomedical applications. However, the internalized NPs inside cells may have some adverse effects. Therefore, the interactions between NPs and cells should be thoroughly investigated and elucidated. This review summarizes the latest advances in NP-cell interactions. Especially the effects of NP properties including size, shape, shell structure, surface chemistry and protein corona formation on cellular uptake and cytotoxicity are highlighted in detail. Their effects on cell proliferation, differentiation and cellular mechanics are also discussed. These insights into NP-cell interactions should provide useful information for the preparation of highly functional NPs and their biomedical applications.

Recent applications of the combination of mesoporous silica nanoparticles with nucleic acids: development of bioresponsive devices, carriers and sensors

Abstract: The discovery and control of the biological roles mediated by nucleic acids have turned them into a powerful tool for the development of advanced biotechnological materials. Such is the importance of these gene-keeping biomacromolecules that even nanomaterials have succumbed to the claimed benefits of DNA and RNA. Currently, there could be found in the literature a practically intractable number of examples reporting the use of combination of nanoparticles with nucleic acids, so boundaries are demanded. Following this premise, this review will only cover the most recent and powerful strategies developed to exploit the possibilities of nucleic acids as biotechnological materials when in combination with mesoporous silica nanoparticles. The extensive research done on nucleic acids has significantly incremented the technological possibilities for those biomacromolecules, which could be employed in many different applications, where substrate or sequence recognition or modulation of biological pathways due to its coding role in living cells are the most promising. In the present review, the chosen counterpart, mesoporous silica nanoparticles, also with unique properties, became a reference material for drug delivery and biomedical applications due to their high biocompatibility and porous structure suitable for hosting and delivering small molecules. Although most of the reviews dealt with significant advances in the use of nucleic acid and mesoporous silica nanoparticles in biotechnological applications, a rational classification of these new generation hybrid materials is still uncovered. In this review, there will be covered promising strategies for the development of living cell and biological sensors, DNA-based molecular gates with targeting, transfection or silencing properties, which could provide a significant advance in current nanomedicine.