电纺技术在生物医学中的应用进展

电纺技术已经成为结合多组分化合物与织造技术的关键工具,可改变电纺丝材料的化学、物理和生物特性,使其与不同的应用环境相适应。通过电纺技术制作的功能化纳米电纺丝材料,在组织工程、创伤敷料、酶的固定化和药物（基因）载体等生物医学方面得到了广泛的应用。新型的电纺技术可以进一步优化纳米电纺丝的特性,如同轴电纺、二相电纺技术;电纺丝膜的修饰也为调控电纺丝的各向异性和多孔性提供了有效的方法。该文将概述功能化电纺丝的纺织技术及修饰方法在生物医学领域的研究与应用进展。     

Two-photon probes for biomedical applications

Two-photon microscopy (TPM), which uses two photons of lower energy as the excitation source, is a vital tool in biology and clinical science, due to its capacity to image deep inside intact tissues for a long period of time. To make TPM a more versatile tool in biomedical research, we have developed a variety of two-photon probes for specific applications. In this mini review, we will briefly discuss two-photon probes for lipid rafts, lysosomes, mitochondria, and pH, and their biomedical applications. [BMB Reports 2013; 46(4): 188-194]     

Luminescent nanodiamonds for biomedical applications

In recent years, nanodiamonds have emerged from primarily an industrial and mechanical applications base, to potentially underpinning sophisticated new technologies in biomedical and quantum science. Nanodiamonds are relatively inexpensive, biocompatible, easy to surface functionalise and optically stable. This combination of physical properties are ideally suited to biological applications, including intracellular labelling and tracking, extracellular drug delivery and adsorptive detection of bioactive molecules. Here we describe some of the methods and challenges for processing nanodiamond materials, detection schemes and some of the leading applications currently under investigation.     

Conductive polymer-based sensors for biomedical applications

A class of organic polymers, known as conducting polymers (CPs), has become increasingly popular due to its unique electrical and optical properties. Material characteristics of CPs are similar to those of some metals and inorganic semiconductors, while retaining polymer properties such as flexibility, and ease of processing and synthesis, generally associated with conventional polymers. Owing to these characteristics, research efforts in CPs have gained significant traction to produce several types of CPs since its discovery four decades ago. CPs are often categorised into different types based on the type of electric charges (e.g., delocalized pi electrons, ions, or conductive nanomaterials) responsible for conduction. Several CPs are known to interact with biological samples while maintaining good biocompatibility and hence, they qualify as interesting candidates for use in a numerous biological and medical applications. In this paper, we focus on CP-based sensor elements and the state-of-art of CP-based sensing devices that have potential applications as tools in clinical diagnosis and surgical interventions. Representative applications of CP-based sensors (electrochemical biosensor, tactile sensing 'skins', and thermal sensors) are briefly discussed. Finally, some of the key issues related to CP-based sensors are highlighted.     

Synthetic oligonucleotides for biomedical applications.

New developments of oligonucleotides for biomedical applications are surveyed. Diagnostic probes were conveniently labelled by enzymatic immunogenic tailing with 5-bromo-deoxyuridine triphosphate. "Antisense" oligonucleotides of potential therapeutic value were stabilized against nucleolytic decay by inversion of terminal internucleotidic linkages. Introduction of 2'-deoxy-2'-fluoro-nucleotide units enhances duplex stability and conveys resistance to ribonucleases.     

Polymer-based stimuli-responsive nanosystems for biomedical applications

The application of organic polymers and inorganic/organic hybrid systems in numerous fields of biotechnology has seen a considerable growth in recent years. Typically, organic polymers with diverse structures, compositional variations and differing molecular weights have been utilized to assemble polymeric nanosystems such as polymeric micelles, polymersomes, and nanohydrogels with unique features and structural properties. The architecture of these polymeric nanosystems involves the use of both hydrophobic and hydrophilic polymeric blocks, making them suitable as vehicles for diagnostic and therapeutic applications. Recently, “smart” or “intelligent” polymers have attracted significant attention in the biomedical field wherein careful introduction of specific polymeric modalities changes a banal polymeric nanosystem to an advanced stimuli-responsive nanosystem capable of performing extraordinary functions in response to an internal or external trigger such as pH, temperature, redox, enzymes, light, magnetic, or ultrasound. Further, incorporation of inorganic nanoparticles such as gold, silica, or iron oxide with surface-bound stimuli-responsive polymers offers additional advantages and multifunctionality in the field of nanomedicine. This review covers the physical properties and applications of both organic and organic/inorganic hybrid nanosystems with specific recent breakthroughs in drug delivery, imaging, tissue engineering, and separations and provides a brief discussion on the future direction.     

Water-soluble quantum dots for biomedical applications

Semiconductor nanocrystals are 1-10nm inorganic particles with unique size-dependent optical and electrical properties due to quantum confinement (so they are also called quantum dots). Quantum dots are new types of fluorescent materials for biological labeling with high quantum efficiency, long-term photostability, narrow emission, and continuous absorption spectra. Here, we discuss the recent development in making water-soluble quantum dots and related cytotoxicity for biomedical applications.     

Light-guided surface engineering for biomedical applications

Free radical species generated through fluorescence photobleaching have been reported to effectively couple a water-soluble species to surfaces containing electron-rich sites . In this report, we expand upon this strategy to control the patterned attachment of antibodies and peptides to surfaces for biosensing and tissue engineering applications. In the first application, we compare hydrophobic attachment and photobleaching methods to immobilize FITC-labeled anti-M13K07 bacteriophage antibodies to the SiO2 layer of a differential capacitive biosensor and to the polyester filament of a feedback-controlled filament array. On both surfaces, antibody attachment and function were superior to the previously employed hydrophobic attachment. Furthermore, a laser scanning confocal microscope could be used for automated, software-guided photoattachment chemistry. In a second application, the cell-adhesion peptide RGDS was site-specifically photocoupled to glass coated with fluorescein-conjugated poly(ethylene glycol). RGDS attachment and bioactivity were characterized by a fibroblast adhesion assay. Cell adhesion was limited to sites of RGDS photocoupling. These examples illustrate that fluorophore-based photopatterning can be achieved by both solution-phase fluorophores or surface-adhered fluorophores. The coupling preserves the bioactivity of the patterned species, is amenable to a variety of surfaces, and is readily accessible to laboratories with fluorescence imaging equipment. The flexibility offered by visible light patterning will likely have many useful applications in bioscreening and tissue engineering where the controlled placement of biomolecules and cells is critical, and should be considered as an alternative to chemical coupling methods.     

Thermal microdevices for biological and biomedical applications

Temperature strongly influences the form and function of biologically important macromolecules and cells. Advances in microfabrication technology have enabled highly localized and accurate temperature control and manipulation, allowing the investigation of thermal effects on biological microsystems. This paper reviews progress in this field, with emphasis on techniques and microdevices with biomedical applications. Recent advances in the study of thermal effects on cellular behavior, enabled by MEMS-based structures are reported. These studies focus on investigating thermal interactions between the cell and its microenvironment. Thermal-based tools for concentration and purification of biologically important macromolecules like DNA and proteins are summarized. These tools address common issues in protein/DNA research, like concentration, separation and purification of samples. With the increasing research focus on the integration of biomedicine with engineering technologies and the several incentives of miniaturization, MEMS-based devices are likely to become increasingly prevalent in biology and medicine. Thermal engineering is expected to continue to play an important role in the improvement of current microdevices and the development of new ones.     

Biochemiluminescence and biomedical applications

Although used for analytical purposes for more than 40 years it is only recently that biochemiluminescence (BCL) has found widespread acceptance. Methods employing BCL reactions now play an important role in biomedical research and laboratory medicine. The main attractions for the assay technology include exquisite sensitivity (attomole-zeptomole), high selectivity, speed and simplicity. In biomedical research, the most important applications of BCL are: (1) to estimate microbial numbers and to assess cellular states (e.g., after exposure to antibiotic or cytotoxic agents) and in reporter gene studies (firefly luciferase gene); (2) NAD(P)H involved in redox/dehydrogenase studies usingVibrio luciferase complex; (3) BCL labels and CL detection of enzyme labels in immunoassays are the most widespread routine application for this technology. BCL enzyme immunoassays represent the most active area of development, e.g., enhanced BCL method for peroxidase and BCL assays for alkaline phosphatase labels using adamantyl 1,2-dioxetane.Abbreviations BCL biochemiluminescence - CL chemiluminescence - RLU relative light unit - ROS reactive oxygen species     

One-step synthesis of polyesters specialties for biomedical applications

Polyesters are widely used for biomedical applications such as drug delivery systems and resorbable implants. The degradation kinetic of these biopolymers can be tailored by the introduction of functional groups in their backbone, leading to a modification of their morphology and hydrophilicity. This is usually realized via long multistep reaction pathways. This contribution describes the emergence of one-step procedures for this purpose including enzymatic and Lewis acid catalyzed polycondensation as well as coordinative ring opening polymerization.     

Next generation organoids for biomedical research and applications

Organoids are in vitro cultures of miniature fetal or adult organ-like structures. Their potentials for use in tissue and organ replacement, disease modeling, toxicology studies, and drug discovery are tremendous. Currently, major challenges facing human organoid technology include (i) improving the range of cellular heterogeneity for a particular organoid system, (ii) mimicking the native micro- and matrix-environment encountered by cells within organoids, and (iii) developing robust protocols for the in vitro maturation of organoids that remain mostly fetal-like in cultures. To tackle these challenges, we advocate the principle of reverse engineering that replicates the inner workings of in vivo systems with the goal of achieving functionality and maturation of the resulting organoid structures with the input of minimal intrinsic (cellular) and environmental (matrix and niche) constituents. Here, we present an overview of organoid technology development in several systems that employ cell materials derived from fetal and adult tissues and pluripotent stem cell cultures. We focus on key studies that exploit the self-organizing property of embryonic progenitors and the role of designer matrices and cell-free scaffolds in assisting organoid formation. We further explore the relationship between adult stem cells, niche factors, and other current developments that aim to enhance robust organoid maturation. From these works, we propose a standardized pipeline for the development of future protocols that would help generate more physiologically relevant human organoids for various biomedical applications.     

Electro-rheological fluids: an introduction for biomedical applications

The subject of electro-rheology is introduced to biological engineers in a concise manner to allow presentation of a procedure for effective quantitative evaluation of possible medical applications of this new technology. More detailed phenomena are included in the references. Characteristics of the current best available fluid are given in brief.     

Acoustic wave based MEMS devices for biosensing applications

This paper presents a review of acoustic-wave based MEMS devices that offer a promising technology platform for the development of sensitive, portable, real-time biosensors. MEMS fabrication of acoustic wave based biosensors enables device miniaturization, power consumption reduction and integration with electronic circuits. For biological applications, the biosensors are integrated in a microfluidic system and the sensing area is coated with a biospecific layer. When a bioanalyte interacts with the sensing layer, mass and viscosity variations of the biospecific layer can be detected by monitoring changes in the acoustic wave properties such as velocity, attenuation, resonant frequency and delay time. Few types of acoustic wave devices could be integrated in microfluidic systems without significant degradation of the quality factor. The acoustic wave based MEMS devices reported in the literature as biosensors and presented in this review are film bulk acoustic wave resonators (FBAR), surface acoustic waves (SAW) resonators and SAW delay lines. Different approaches to the realization of FBARs, SAW resonators and SAW delay lines for various biochemical applications are presented. Methods of integration of the acoustic wave MEMS devices in the microfluidic systems and functionalization strategies will be also discussed.     

Carbon dioxide induced silk protein gelation for biomedical applications

We present a novel method to fabricate silk fibroin hydrogels using high pressure carbon dioxide (CO(2)) as a volatile acid without the need for chemical cross-linking agents or surfactants. The simple and efficient recovery of CO(2) post processing results in a remarkably clean production method offering tremendous benefit toward materials processing for biomedical applications. Further, with this novel technique we reveal that silk protein gelation can be considerably expedited under high pressure CO(2) with the formation of extensive β-sheet structures and stable hydrogels at processing times less than 2 h. We report a significant influence of the high pressure CO(2) processing environment on silk hydrogel physical properties such as porosity, sample homogeneity, swelling behavior and compressive properties. Microstructural analysis revealed improved porosity and homogeneous composition among high pressure CO(2) specimens in comparison to the less porous and heterogeneous structures of the citric acid control gels. The swelling ratios of silk hydrogels prepared under high pressure CO(2) were significantly reduced compared to the citric acid control gels, which we attribute to enhanced physical cross-linking. Mechanical properties were found to increase significantly for the silk hydrogels prepared under high pressure CO(2), with a 2- and 3-fold increase in the compressive modulus of the 2 and 4 wt % silk hydrogels over the control gels, respectively. We adopted a semiempirical theoretical model to elucidate the mechanism of silk protein gelation demonstrated here. Mechanistically, the rate of silk protein gelation is believed to be a function of the kinetics of solution acidification from absorbed CO(2) and potentially accelerated by high pressure effects. The attractive features of the method described here include the acceleration of stable silk hydrogel formation, free of residual mineral acids or chemical cross-linkers, reducing processing complexity, and avoiding adverse biological responses, while providing direct manipulation of hydrogel physical properties for tailoring toward specific biomedical applications.