Lignin Composites for Biomedical Applications: Status, Challenges and Perspectives

Optical Bioimaging and Therapy

Over the past few decades, chitosan (CS) has gained the attention of researchers investigating newer biomaterial-based carriers for drugs in pharmaceutical and biomedical research. Combined with its nontoxic behavior, biodegradability, and biocompatibility, chitosan has found widespread applications in the fields of drug delivery, tissue engineering, and cosmetics. As a novel drug carrier, chitosan is regarded as one of the promising biomaterials in the pharmaceutical industry. The extensive use of this cationic biopolysaccharide in the delivery of therapeutic agents has brought a few limitations of chitosan into the limelight. Various chemical modifications of chitosan can minimize these limitations and improve the efficacy of chitosan as a drug carrier. The effectiveness of several chemically modified chitosan derivatives, including trimethyl chitosan, thiolated chitosan, PEGylated chitosan, and other chitosan derivatives, has been investigated by many researchers for the controlled and target specific delivery of therapeutics. The chemically modified chitosan derivatives exhibited greater importance in the current scenario on drug delivery due to their solubility in wide range of media along with their interaction with pharmaceutically active ingredients. Chitosan derivatives have also attracted attention in several biomedical fields, including wound healing, hyperthermia therapy, tissue engineering, and bioadhesives. The present review narrates the sources and common physicochemical properties of chitosan, including several important synthetic modifications to obtain chemically modified chitosans and their applications in target-specific drug delivery, along with several biomedical applications.

Fullerene C60, an allotrope of carbon cage-like structure, exhibits unique physical and chemical properties, which show great potential for many biomedical applications. The fullerene surface can be functionalized with various chemical functional groups (like -NH2, -OH, -COOH) and modified with peptides and other biomolecules. The functionalized fullerene derivatives are known to exhibit anticancer, antimicrobial, and various other biomedical applications. Fullerene and its products represent a group of compounds with unique properties like flexible backbone structure that can be readily derivatized, high surface area, and stability. Fullerene and its derivatives are known to be biocompatible with reduced toxicity when used in biomedical applications. The unique physicochemical properties like high surface area and pore volume make them essential candidates for drug delivery applications. Therefore, the current chapter highlights various fullerene derivatives with different functionalization strategies and their efficient use as potential drug delivery carriers, especially in anticancer applications.

Background: Biodegradable stimuli-responsive materials, which exhibit large and sharp physical–chemical changes in response to small physical or chemical stimuli, are attracting increasing interests because of their potential applications in biomedical fields, such as transient implants, drug delivery carriers, and tissue engineering scaffolds. Our previous review (see page 493 of issue 4) summarized those biodegradable ‘intelligent’ materials that respond to physical stimuli, such as temperature, ultrasound, and magnetic field. Biodegradable ‘intelligent’ materials that could respond to chemical stimuli, such as pH and specific molecules, have also been studied intensively and significant progress in this field has been achieved. As a single stimulus-responsive property would limit practical application, multi-stimuli-responsive materials are receiving increasing interest and considerable attention. Objective/methods: This review summarizes the development of biodegradable ‘intelligent’ materials in response to chemical stimuli and to dual stimuli; their potential biomedical applications are also introduced. A detailed analysis of publications and patents on such materials in recent years is presented. Results/conclusion: Most of biodegradable stimuli-responsive materials are currently still at a developmental research stage. Further work is required to improve the responsive properties between the materials and the biological environments, so that the clinical applicability of such devices could be successful. We hope that our review will be helpful in the future development of new stimuli-responsive biodegradable polymers or polymeric systems that can be used reliably in real-life applications.

Event Abstract Back to Event Preparation and cellular uptake of thermoresponsive transformable nanoparticles Akihiko Kikuchi1*, Takuma Suzuki1*, Takuya Matsuyama1*, Ryo Ishihara1* and Taka-Aki Asoh2* 1 Tokyo University of Science, Department of Materials Science and Technology, Japan 2 Osaka City University, The OCU Adv. Res. Inst. of Natural Sci. & Technol., Japan Nanoparticles have widely been utilized in both technological and biomedical applications because of their favorable size and quite large specific surface area. These nanoparticles are used as drug delivery carriers and as diagnostic device in biomedical fields. We have been working on the synthesis of thermoresponsive nanoparticles[1]. Akashi and co-workers presented sophisticated nanoparticle preparation so called “macromonomer method” to prepare core-corona type nanoparticles[2]. We have applied this method for preparation of core-corona type nanoparticles with thermoresponsive polymer with well-difined molecular weight as corona segments on nanoparticles’ surfaces. Atom transfer radical polymerization (ATRP) was applied for preparation of poly(N-isopropylacrylamide) (PNIPAAm) having number-averaged molecular weight of 3000 to 18000 with PDI below 1.15. These were then transformed to PNIPAAm macromonomers by end group functionalization. PNIPAAm macromonomer was then copolymerized with butyl methacrylate (BMA) to prepare core-corona type nanoparticles [3]. PBMA was used as core segments since PBMA has Tg at 20 °C. Thermoresponsive diameter change was observed, indicating that PNIPAAm chains existed around the particles’ surfaces[1],[3]. We then tried to change particle shape by temperature[3]. Rod shaped PBMA-g-PNIPAAm nanoparticles was prepared by uniaxial extention. As shown in Figure 1, these particles remain unchanged at 4°C while by incubating nanoparticles above the core Tg, shape returned from rod to sphere. Introduction of methyl methacrylate (MMA) to the core resulted in increased core Tg for up to 32°C. Rate for the shape change from rod to sphere was controlled by difference between incubation temperature and core Tg. Figure 2 shows number of particles internalized in mouse RAW264.7 macrophage. At 25°C spherical particles showed weaker interaction with cells since these have hydrophilic surfaces while at 37°C more spheres are internalized into cells due to hydrophobized nature of particles. To the contrary, rod shaped particles showed smaller interaction than spherical ones regardless of temperature. Thus cell-nanoparticle interaction can be modulated by both temperature-dependent shape change and surface property alteration of prepared thermoresponsive nanoparticles. Rod-shaped particles are reported to not phagocytized by cells while spherical particles are phagocytized[4]. As prepared nanoparticles possess temperature responsive shape and surface property changes, these would be useful in theragnostics by stimuli-responsive internalization to cells. Casio Science Foundation (2013-2014); Center for Physical Pharmaceutics, Tokyo Univ. of Science (2010-2015)

4 - Medical applications

Recent progress of rare earth doped hydroxyapatite nanoparticles: Luminescence properties, synthesis and biomedical applications

A review on biomedical and dental applications of cerium oxide nanoparticles ― Unearthing the potential of this rare earth metal

Lignocellulosic biomasses are strongly connected composites of cellulose, hemicelluloses, and lignin. A pretreatment is required in order to make these components available for their later conversion into chemicals. At this point, two strategies have to be considered: to either produce chemicals via microorganism or enzymes (1), or by chemical conversion (2). The focus of this article is the second strategy, which is chemical conversion, performed in water to produce the final products furfural and 5-hydroxymethylfurfural (HMF). Reviewed first is the composition of cellulose and hemicelluloses as well as their degradation chemistry in water. Then, fundamental modes of action and process parameters of pretreatment methods in aqueous solution are summarized. The pretreatment methods discussed here are steam explosion, treatment with hot liquid water, diluted and concentrated acids, as well as alkaline solutions. Finally, the advantages and disadvantages of these pretreatments are discussed for lignocellulosic biomass.

Polyimides have inherently high mechanical properties, good chemical resistance, a low dielectric constant and high thermal stability [1]. In recent years, polyimide-based sensor materials have received much attention due to their simple preparation method, chemical inertness, mechanical and thermal stability, and high biocompatibility[2–4]. Thus they have a wide range of diverse and potential applications in several major technologies. Among the polymers, polyimides (PI) possess reliable high-temperature stability, excellent chemical resistance, high hydrolytic stability, adhesive properties, and good mechanical strength [7– 9]. Polysulfones and phosphine oxidecontaining polyimides have excellent adhesive properties without sacrificing thermal stability [10–12].

Recent advances in the development of novel nanomaterials and evaluation of their biomedical applications have shown promises of those multifunctional nanomaterials in the development of new approaches for cancer detection and therapy. The unique physicochemical properties of nanomaterials, small size, and large surface-area-to-volume ratio endow them with novel multifunctional capabilities for cancer imaging, drug delivery, and cancer therapy, referred to as theranostics, which are different from the traditional diagnosis and therapy approaches. To facilitate the translation of nanomaterials as imaging agents and drug delivery carriers into clinical applications, great efforts have been made on designing and improving biocompatibility, stability, safety, drug loading ability, targeted delivery, imaging signals, and thermal- or photodynamic responses. With the development of companion new imaging techniques and therapeutic approaches, several nanomaterials have demonstrated great theranostic potential in image-guided therapy of diseases, especially in cancer therapy. In this review, the current status and perspective of nanoparticles in the development of cancer theranostic agents will be discussed with a focus on several representative nanomaterials, including magnetic iron oxide nanoparticles, gold nanoparticles, silica nanoparticles, polymeric nanoparticles, and carbon nanomaterials.

Chapter 10 - Silk fiber composites in biomedical applications

The development of architectured nanomaterials has been booming in recent years in part due to their expanded applications in the biomedical field, such as biosensing, bioimaging, drug delivery, and cancer therapeutics. Nanomaterials exhibit a wide variety of shapes depending on both the intrinsic properties of the materials and the synthesis procedures. Typically, the large surface areas of nanomaterials improve the rate of mass transfer in biological reactions. They also have high self-ordering and assembly behaviors, which make them great candidates for various biomedical applications. Some nanomaterials have a high conversion rate in transforming the energy of photons into heat or fluorescence, thus showing promise in cancer treatment (such as hyperthermia) and bioimaging. The nanometric dimension makes them suitable for passing through the biological barriers or interacting with the natural molecules (such as DNA, protein). Nanoflowers, nanotrees, nanostars, and nanodendrites are examples of nano-sized structures, which exhibit unique geometry-dependent properties. Here we reviewed the fabrication methods, features, properties, and biomedical applications of four nano-structured materials including nanoflowers, nanotrees, nanostars, nanodendrites, and nanoleaves. We further provided our perspectives on employing these novel nanostructures as advanced functional materials for a broad spectrum of applications.

Biomedical Applications of Electrospun Polymer and Carbon Fibers ,

Carbon nanotubes: Types, synthesis, cytotoxicity and applications in biomedical