FP - 12th International Conference
Medical Applications of Advanced Biomaterials and Nano-biotechnology

Session FP-1 - Advances in Biomaterials

FP-1:IL01  Advanced Bioactive Structures for Intervertebral Disc Repair/Regeneration
L. AMBROSIO, A. GLORIA, Institute of Polymers, Composites and Biomaterials, National Research Council, Naples, Italy

Intervertebral disc (IVD) degeneration is one of the main causes of low back pain. Current surgical treatments are complex and generally do not fully restore spine mobility. Development of injectable extracellular matrix-based hydrogels offers an opportunity for minimally invasive treatment of IVD degeneration. Due to the complex structure and function of the IVD, the tissue engineering of a disc substitute represents a challenge from mechanical and biological (nutrition and transport) points of view. Here we analyze a specific formulation of hyaluronans and collagen-low molecular weight hyaluronic acid semi-interpenetrating network loaded with gelatin microspheres, as a potential materials for tissue engineering of the nucleus pulposus (NP). The material displayed a gel-like behavior, it was easily injectable as demonstrated by suitable tests and did not induce cytotoxicity or inflammation. Importantly, it supported the growth and chondrogenic differentiation potential of mesenchymal stem cells (MSC) in vitro and in vivo. Moreover, 3D additive manufactured IVD system was fabricated through 3D fiber deposition technique.
Acknowledgements This work was funded under the EU-FP5 Contract No. G5RD-CT-2000-00267 and EU FP7 Grant No. NMP3-LA-2008-213904.


FP-1:IL02  Shape Memory Activated Polyelectrolyte Nano-wrinkles Improve Fibroblast Cell Attachment and Alignment
P.T. MATHER, Chemical Engineering, Bucknell University, Lewisburg, PA, USA; A. ASH-SHAKOOR, J.H. HENDERSON, Biomedical and Chemical Engineering, Syracuse University, USA

The need exists for effective, reproducible, and simple approaches to the creation of polymeric surfaces that direct the behavior of adherent cell for tissue engineering application. Past work in this area has revealed that both substrate chemistry and topography greatly impact cell behavior, ranging from cell spreading to motility and alignment. Optimizing these variables is essential for the fabrication of substrates for biomaterial and smart scaffold applications. We have designed a new material that combines shape memory polymers (SMPs) with polyelectrolyte multilayer (PEM) coatings to yield charged surfaces with nanoscale wrinkles that interact strongly with adherent cells. A strained SMP was coated with a PEM terminated with positive or negative charge. Application heat, led to wrinkle formation due to compression of the PEM coatings. We then studied the behavior of mouse fibroblast cells (C3H10T1/2) on the materials, revealing success in achieving high nuclear orientation of the fibroblast cells and an ability to manipulate both motility and orientation.


FP-1:IL03  Development of a Fish Gelatin-based Soft Tissue Adhesive for Biomedical Applications
TETSUSHI TAGUCHI, RYO MIZUTA, Biomaterials Field, Research Center for Functional Materials, National Institute for Materials Science, Japan

Surgical adhesives have been widely used in clinical field for the treatment of pulmonary air leaks and anastomotic sites between living tissues. Fibrin adhesive is a typical adhesive which consists of human blood components and has excellent biocompatibility and versatile, however, it does not possess sufficient sealing effect because of its low interfacial bonding strength to tissues. Therefore, the molecular design is required for the adhesive to adhere onto a living tissue and organs under wet environment during surgery. We previously developed a tissue adhesive containing hydrophobically modified porcine-derived gelatin with excellent bonding strength as well as biocompatibility. However, porcine-derived gelatin solution with high concentration has low fluidity at room temperature because and is required heat treatment before using adhesive. In this study, we have chosen Alaska pollock-derived gelatins (ApGltn) instead of porcine-derived gelatin as a base material for surgical adhesives because it has low transition temperature. We synthesized various hydrophobically modified ApGltns (Hm-ApGltn) with different hydrophobic groups and evaluated their sealing effects on wet tissues by combining Hm-ApGltns with polyethylene glycol-based 4-armed crosslinker.


FP-1:IL05  Cellular and Tissue Modulation via Exploiting Molecularly Movable Polyrotaxane Surfaces 
NOBUHIKO YUI, J.-H. SEO, A. TAMURA, Y. ARISAKA, Tokyo Medical and Dental University, Tokyo, Japan; T. YAMAOKA, S. KAKINOKI, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan

We have clarified that molecularly movable polyrotaxane (PRX) surfaces can regulate small GTPase proteins of adhering cells in relation to their mobility at hydrated states. In particular, it is the most striking feature that down-regulated RhoA-ROCK and up-regulated Rac1/cdc42 are observed for directing stem cell fate on the PRX surfaces with increasing the molecular mobility. Eventually, osteogenic and adipogenic differentiation from mesenchymal stem cells and cardiomyocyte differentiation and beating colony formation from iPS cells have been already demonstrated on the PRX surfaces with a variety of molecular mobility. Alternatively, it has been found that the molecular mobility is effective to maintain the biological activity of tethered growth factors such as BMP-2 on the PRX surfaces for osteogenic differentiation and bone regeneration. Finally, it is concluded that molecularly movable PRX surfaces can perform far-reaching consequences in modulating a variety of cellular and tissue functions.


FP-1:IL06  Development of Novel Antibacterial Nanoparticles Suitable for Coating on Intravascular Catheters
TSUTOMU FURUZONO, Department of Biomedical Engineering, Faculty of Biology-Oriented Science and Technology, Kindai University, Kinokawa, Japan

Catheters impregnated with strong antibacterial chemical agents have not been available in Japan, because patients equipped chlorhexidine-silver sulfadiazine-impregnated catheters experienced serious anaphylactic shock. Thus, it is necessary to develop a novel coating material possessing weak antibacterial activity being difficult to happen the shock. Hydroxyapatite (HAp) is biocompatible to bone and skin tissues. In order to provide weak antibacterial activity, fluorine (F) ions were doped to the HAp structure. Highly dispersed F-doped HAp (F-HAp) nanoparticles suitable as a coating material were developed. It was clear that the stability of F-HAp was higher than that of original HAp in the acid resistance test. The antibacterial activity of F-HAp using E. coli was much weaker than that of Ag-doped HAp (Int J Artif Organs 251; 38: 251-258). In anaphylactic shock test in vitro, the concentration of histamine secreted from human mast cell (HMC-1) with addition of F-HAp was lower compared to chlorhexidine and almost equal to the cell alone. Thus, the dispersed F-HAp nanoparticles possessing weak antimicrobial activity can be useful without severe damage to living tissue.
Financial support: The study was supported in part by JSPS Grant-in-Aid for Scientific Research (C) (KAKENHI).


FP-1:IL07  Implementing Multifunctionality in Polymer-based Biomaterials
A. LENDLEIN^1,2, ¹Institute of Biomaterial Science and Berlin-Brandenburg Centre for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany; ²University of Potsdam, Potsdam, Germany

Modern medicine aims at causal and gentle therapies. Especially minimally invasive procedures as well as regenerative therapies receive increasing attention. Here multifunctional materials play a key role. In this presentation strategies are introduced to create polymer based systems, in which different material properties and functions can be adjusted almost independently from each other by only small variations in their chemical composition. Polymer network architectures allow modular approaches for the creation of multifunctional polymers on the molecular level. Three dimensional structures of shaped bodies, such as foams or multimaterial systems, offer additional options to implement further functions associated to different hierarchical organization levels. These principles are illustrated by examples such as gelatine-based 3D architectured hydrogels, multiblock copolymers or nanocomposites. Besides structural functions different shape-memory capabilities, degradability and biofunctionality are considered and potential applications are discussed.


FP-1:IL08  Design of Adhesive Growth Factors 
YOSHIHIRO ITO, Nano Medical Engineering Laboratory, RIKEN, Japan Emergent Bioengineering Materials Research Team, RIKEN Center for Emergent Matter Science, Japan

Adhesive growth factors are attractive for design of bioactive materials, because they activate cell growth and differentiation through the signal transduction. By the surface modification using the proteins the long-lasting effect without cellular internalization and the high local concentration on the surface are expected to induce significant biological effects on cells. We have designed various adhesive growth factors including EGF, IGF, VEGF, HGF, and BMP by several approaches using molecular evolutionary engineering and bio-orthogonal chemistry. The molecular evolutionary engineering provides targeting activity and bio-orthogonal approach non-specific adhesiveness onto both organic and inorganic materials. The methodology will be important for future development of biomaterials and matrices for tissue engineering.


FP-1:L09  Next Generation Nanofiber Structures for Regenerative Engineering
N. NAGIAH, L.S. NAIR, C. LAURENCIN, M. BHATTACHARJEE, The Institute for Regenerative Engineering, University of Connecticut Health Center, University of Connecticut, Farmington, CT, USA

An ideal design for biomimetic structures mimicking the properties of extracellular matrix would entail matrices with high structural stability, possessing physical and biochemical cues that can influence the regenerative process. We have explored the development of novel coaxial core-sheath nanofibers possessing physical and biochemical attributes that make them attractive for regenerative engineering applications. The design of these coaxial nanofibers can create important possibilities for simultaneous drug delivery and tissue. The introduction of an additional layer has been performed in effect creating triaxial nanofibers that more precisely allow for control of material and biochemical properties. These new next generation nanofiber matrices are designed for robust applications in regenerative engineering.


FP-1:IL12  Calcium Phosphate Surfaces and Bone Regeneration
C. STAEHLI, M. BOHNER, RMS Foundation, Bettlach, Switzerland

Interfaces between biomaterials and biological tissues have been extensively studied over the past 50 years. Aspects of interest have been numerous, such as the effect of surface topography, hydrophilicity, or composition on the biological response. Calcium phosphate materials have been used as bone graft substitutes since the 1970’s. These materials are often considered to be the best biomaterials for such applications. Surprisingly, very little is known on the link between calcium phosphate properties and their biological response. In the past ten years, we have been able to show that calcination at ≈500°C modifies the chemical and biological response of β-tricalcium phosphate, α-tricalcium phosphate, and hydroxyapatite. Most recent investigations suggest that these changes are likely due to chemical changes at the surface, such as phosphate depletion. The aim of my talk will be to review past and present activities of my group in trying to understand and control the link between calcium phosphate surface chemistry and reactivity. Topics such as thermal treatments and impurity levels will be addressed.


FP-1:IL13  Programmable Biomaterials for Mechanobiology
J.H. HENDERSON, Syracuse Biomaterials Institute, Syracuse University, Syracuse, NY, USA

Recent advances in programmable biomaterials are enabling new investigations and understanding in mechanobiology—the study of how physical forces at the cell and tissue level contribute to development, maintenance, wound healing, and disease. A major focus of our work in this area is the development and application of cytocompatible shape memory polymers for the study of cell mechanobiology. Having developed cytocompatible two-dimensional shape memory polymer substrates and three-dimensional shape memory polymer scaffolds, we are using these programmable biomaterials to investigate cell mechanobiology at the level of organelles, individual cells, and populations of cells. Current work demonstrating the development, characterization, and application of these programmable materials, as well as the new insights into cell mechanobiology that they are enabling, will be presented.


FP-1:L14  Fabrication and Evaluation of Beta-tricalcium Phosphate Granules Cement
KUNIO ISHIKAWA, Dept. of Biomaterials, Faculty of Dental Science, Kyushu University, Fukuoka, Japan

In situ fabrication of the interconnected porous structure with calcium phosphate at the bone defect is an ideal method for bone reconstruction. One of the methods of porous structure fabrication is a packing of granules. On the other hand, brushite is a calcium phosphate stable in acidic pH. Therefore, brushite is formed on the surface of beta-tricalcium phosphate (TCP) granules when TCP granules are mixed with acidic solution, and the brushite bridges the TCP granules each other to form interconnected porous β-TCP. We propose this as TCP granules cement (GC). In this study, monocalcium phosphate monohydrate saturated H3PO4 (Ca-PO4) solution and NaHSO4 solution were used as acidic solutions. When TCP granules were mixed with Ca-PO4 solution, only brushite is formed whereas brushite and calcium sulfate dihydrate (CSD) is formed when TCP granules were mixed with NaHSO4 solution. Amount of the precipitate increase with solution concentration. Interestingly, DTS value of set TCPGC was almost the same, 0.6MPa, regardless of the Ca-PO4 solution concentration. In contrast, in the case of TCPGC using NaHSO4, DTS value increased with the NaHSO4 concentration to reach 2MPa when 5 mol/L NaHSO4 was used. We concluded, CSD play important role for the higher mechanical strength.


FP-1:L16  Synthesis and Characterization of Copper Oxide Based Polymeric Nano-systems for Biomedical Imaging
I.S. WEITZ¹, O. PERLMAN², S.S. SIVAN¹, H. AZHARI², ¹Department of Biotechnology Engineering, ORT Braude College, Karmiel, Israel; ²Department of Biomedical Engineering, Technion-Israel Institute of Technology, Technion City, Haifa, Israel

The unique properties of copper oxide (CuO) nanoparticles (NPs) have attracted great interest for the treatment of infectious diseases, cancer and as contrast agents for medical imaging. Further study of the potential clinical use mainly concerns with controlling CuO release in the targeted site to avoid adverse effects and improving therapeutic and diagnostic outcomes. This work focuses on the design and synthesis of innovative and safe CuO-based nano-systems (CuO-NPs-NS), capable of performing imaging and therapeutic tasks simultaneously. To this aim, CuO NPs were encapsulated in a biodegradable polymeric matrix by the double emulsion/solvent evaporation technique. The yielded spherical nanostructures were characterized by TEM, DLS, FTIR, ICP, TGA and zeta potential. CuO-NPs-NS, 150-300 nm in diameter and loading of 4-12% Cu, were also found to greatly enhance MR/ultrasound imaging contrast in in vitro, ex vivo, and in vivo settings. Furthermore, a significant heating effect was produced during the therapeutic ultrasound transmission. The proposed theranostic system can be used as a potential platform for a combined ultrasound-guided imaging and hyperthermia procedures.
Acknowledgment: The research was supported by the Ministry of Science, Technology and Space, Israel (311876)

 
Session FP-2 - Tissue Engineering and Regenerative Medicine

FP-2:IL02  Guided Bone/Tendon Regeneration by Growth Factor-Immobilized Asymmetrically Porous Membranes
JIN HO LEE, Hannam University, Daejeon, South Korea

Insufficient repair of bone-to-tendon interface (BTI) with structural/compositional gradient has been a significant challenge in orthopedics. In this study, growth factors [platelet-derived growth factor-BB (PDGF-BB) and/or bone morphogenetic protein-2 (BMP-2)]-immobilized polycaprolactone (PCL)/Pluronic F127 asymmetrically porous membranes were prepared to estimate their feasibility as a potential strategy for effective regeneration of the BTI injury. The growth factors immobilized (via heparin-intermediated interactions) on the membrane were continuously released for up to ~80% of the initial loading amount for 5 weeks without significant initial burst. From the in vivo animal study, it was observed that the PDGF-BB/BMP-2-immobilized membrane accelerates the regeneration of the BTI injury, probably due to the continuous release of both growth factors (biological stimuli) and their complementary effect to create multiphasic structure (bone, fibrocartilage, and tendon) like native one as well as the roles of the asymmetrically porous membrane as physical barrier (nano-pore side; prevention of fibrous tissue invasion into defect site) and scaffold (micro-pore side; guidance for tissue regeneration).


FP-2:IL04  Cell Migration Mediated by Gradient Cues in Biomaterials
CHANGYOU GAO, Zhejiang University, Hangzhou, China

The processes of tissue regeneration and remodeling depends strongly on the cell migration and differentiation. It is of paramount importance to understand the impact of the structure and property of biomaterials on cell mobility, and subsequently design functional biomaterials for the defined cell migration such as directional movement with tunable mobility. Cell migration is a dynamic process involving multiple interactions between substrates/biomaterials and cells through trans-membrane receptors such as integrin. In the past decade, we have been focusing on the following topics in terms of gradient biomaterials and cell migration: (1) preparation and characterization of several types of gradient biomaterials with continuous changes in grafting density, chain length and swelling properties; (2) Influence of physicochemical properties of gradient biomaterials on cell migration in terms of rate and direction; (3) directional migration of cells under the guidance of gradient cues; (4) selective adhesion of cells and directed migration; and (5) 3D migration of cells guided by chemoattractants in situ secreted by inflammatory cells.


FP-2:IL05  Polymeric and Biomimetic Porous Scaffolds for Tissue Engineering
GUOPING CHEN, NAOKI KAWAZOE, Research Center for Functional Materials, National Institute for Materials Science, Ibaraki, Japan

Porous scaffolds have been used to control cell functions for tissue engineering. Biodegradable synthetic polymers such as PLLA and PLGA and naturally derived polymers such as collagen and gelatin have been the most frequently used biodegradable polymers. Cell-derived extracellular matrices have also been frequently used to prepare biomimetic scaffolds. We have developed a few types of porous scaffolds by using biodegradable polymers and extracellular matrices. The first type is porous scaffolds prepared with ice particulates. This type of scaffolds had well interconnected pore structures. The second type is hybrid scaffolds of synthetic polymers and naturally-derived polymers. Collagen sponge or microsponges were introduced in the pores or openings of mechanically strong PLLA or PLGA porous skeletons to construct the hybrid structures. The PLLA or PLGA skeletons provided high mechanical strength, while the collagen sponge and mircosponges facilitated cell seeding and distribution. The third type is biomimetic ECM scaffolds prepared from cultured cells. Composition of the ECM scaffolds was dependent on the cell type and cell phenotype that were used to prepare the scaffolds. These porous scaffolds were used for 3D culture of fibroblasts, chondrocytes and bone marrow-derived MSCs for tissue engineering of dermal tissue, muscle, cartilage and bone.


FP-2:L07  Injectable Amnion Membrane Hydrogels for Musculoskeletal Regenerative Engineering
M. BHATTACHARJEE, J.L. ESCOBAR IVIRICO, H.M. KAN, L.S. NAIR, C.T. LAURENCIN, Institute for Regenerative Engineering, University of Connecticut Health Center, Farmington, CT, USA  

There is great interest in the design and use of biomimetic injectable hydrogels which can simulate the native tissue microenvironment by providing appropriate biological and chemical cues for regenerative engineering applications. Injectable hydrogels are well known for their ability to self-assemble in situ allowing for minimally invasive surgical delivery systems for treating osteochondral defects. We have fabricated and characterized novel injectable hydrogels made from amnion membrane (AM). The unique advantages of AM include the presence of cell adhesive proteins, anti-inflammatory cytokines, and glycosaminoglycans makes it an ideal candidate for fostering tissue regeneration. AM was isolated from placental tissues, decellularized and lyophilized. AM was solubilized and subsequently modified to form an injectable hydrogel under physiological pH, salt concentration, and temperature. The AM gels were then investigated as part of a stem cell delivery system. Adipose derived stem cells (ADSCs) were encapsulated within AM gels. The AM gels supported the viability, proliferation and stemness of ADSCs. Overall the novel injectable AM hydrogel system is a promising technology for musculoskeletal regenerative engineering.


FP-2:L08  Preparation, Characterization and In Vivo Performance of Decellularized Cornea
AKIO KISHIDA, Y. HASHIMOTO, J. NEGISHI, K. NAM, T. KIMURA, S. SASAKI, Tokyo Medical and Dental University, Tokyo, Japan; S. SASAKI, T. HONDA, S. HATTORI, H. KOBAYASHI, NIMS, Ibaraki, Japan

The ideal scaffold for corneal tissue engineering would allow epithelization, endothelialization, and repopulation with autologous interstitial cells. One strategy for preparing a scaffold is the use of decellularized tissue in which the donor cells and antigen molecules are completely removed to diminish the host immune reaction. We developed a physical process that uses high hydrostatic pressure (HHP) technology to decellularize tissue without using detergents. Porcine corneas were hydrostatically pressed at 980 MPa. We also investigated the influence of HHP on the decellularization of the corneal ultrastructure and its involvement in transparency. Transmission electron microscopy revealed that the ultrastructure of the decellularized cornea prepared by the HHP method was maintained. The in vivo behavior of the decellularized cornea was observed by using deep anterior lamella keratoplasty (DALK). model. The decellularized corneal matrices were opaque immediately after transplantation, but became completely transparent after 4 months. Histological sections revealed that the implanted decellularized corneal matrix was completely ntegrated with the receptive rabbit cornea. The decellularized corneal matrix is promising material for treatment of corneal disease.

 
Session FP-3 - New Therapeutics and Intelligent Drug/Biomolecule/Gene Delivery Systems

FP-3:IL01  Rational Design of Polyrotaxanes as a Therapeutic Agent to Metabolic Diseases
ATSUSHI TAMURA, NOBUHIKO YUI, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo, Japan

β-cyclodextrin (β-CD) derivatives have received much attention because recent studies revealed that β-CDs show therapeutic effect in many diseases, such as Niemann-Pick type C (NPC) disease. NPC disease is a fatal metabolic disorder characterized by the lysosomal accumulation of cholesterol. Although hydroxypropyl β-CD (HP-β-CD) promotes the excretion of lysosomal cholesterol to prolong the life span in animal models of NPC disease, it requires extremely high dose. We developed acid-labile β-CD-threaded polyrotaxanes (PRXs) composed of multiple β-CDs threaded along a linear polymer chain capped with acid-cleavable stopper molecules, for potentiating therapeutic efficacy. The acid-labile PRXs undergo dissociation under the acidic lysosomes and release threaded β-CDs, which promotes cholesterol excretion in NPC disease model cells at lower concentration than HP-β-CD. In this study, we examined the therapeutic effect of the PRXs in a mouse model of NPC disease. Weekly administration of the PRXs significantly prolonged the life span and suppressed the tissue accumulation of cholesterol in mice at a markedly lower dose than HP-β-CD. Acid-labile β-CD-threaded PRX is therefore a promising candidate for potentiating the efficacy of β-CD in the treatment of NPC disease.


FP-3:IL02  Novel Multifunctional Drug and Gene Delivery Systems based on Supramolecular Self-assembled Macromolecules
JUN LI, Department of Biomedical Engineering, National University of Singapore, Singapore

Supramolecular host-guest chemistry has offered a powerful and convenient approach for fabricating complicated nanostructures self-assembled from individually tunable molecular building blocks. In the meantime, it has been a challenge to incorporate multiple functional features into a single gene carrier system to overcome numerous hurdles during the gene delivery. Usually, controlling molecular architectures and compositions of a multi-functional gene carrier for optimizing delivery efficiency requires multi-step chemical synthesis and conjugation processes. Herein, we demonstrate a supramolecular approach for building multifunctional gene carrier systems with controllable molecular architectures based on the host-guest chemistry of β-cyclodextrin (β-CD). This delivery system is composed of two molecular building blocks: one host polymer and one guest polymer, which can self-assemble to integrate multiple functions into one carrier system, based on the host-guest interaction between β-CD and adamantyl moieties in the host and guest, respectively. It was revealed that the properties of the gen carrier were all greatly enhanced by the novel design, resulting in a highly efficient gene delivery system.


FP-3:IL03  Intracellular Delivery of Nanocarriers and Targeting to Subcellular Organelles
V. TORCHILIN, Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA, USA 

Targeted delivery of drug-loaded nanopreparations to target cells and their subsequent delivery inside cells might still further improve the efficiency of therapy. Thus, coupling of cell-penetrating peptides (CPP) to various molecules or even to nanoparticles, such as liposomes, facilitates their intracellular delivery. Similar effect could be achieved using phage coat fusion proteins from the phages selected for their specificity towards target cells. Intracellular drug delivery with subsequent organelle targeting opens new opportunities in overcoming problems associated with multiple pathologies including lysosomal storage diseases and multidrug resistance (MDR) tumors. Delivery of deficient enzymes for the treatment of lysosomal diseases evidently requires specific targeting of lysosomes, while facilitating apoptotic cell death in MDR tumor would require targeting of mitochondria or lysosomes. Thus, next generation drug delivery systems should be able to target individual organelles inside cells. Clearly, this challenge will require some novel approaches in engineering multifunctional nanomedicines, capable of accumulating in the target tissue, penetrating inside cells, bypassing lysosomes, and bringing pharmaceuticals to individual organelles. Examples of specific targeting of pharmaceutical nanosystems to lysosomes and mitochondria illustrate the benefits of this new approach.


FP-3:IL04  “Borono-lectin” Engineering as a Versatile Platform for Intelligent Drug Delivery Systems
AKIRA MATSUMOTO, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo, Japan

Boronic acids (BA) are well known for their ability to reversibly interact with the diol groups, a common motif of biomolecules including sugars and ribose. For its carbohydrate-binding capability, BA can be regarded as a synthetic mimic of lectins, termed “borono-lectin”. One can tailor the “borono-lectin” to elicit a divergent profile of binding strength and specificity on the basis of stereochemistry and controlled electronic effect. Moreover, thanks to recent advancement of Suzuki-Miyaura coupling chemistry, there is an ever-increasing lineup of BA derivatives that are accessible for reasonable price. Besides the versatility, some groups of BA can undergo a sharp inversion in the state of hydration in synchronization with the molecular recognition. This feature, especially when combined with amphiphilic type of polymeric backbone, further widen the utility of BA in materials engineering, providing many creative principles for fine-tuning or switching the hydration and more complex molecular assemblies in a way interactive with biology. I will provide a brief overview of our recent efforts on the related applications, including intracellular environment-selective delivery of siRNA, sialic acid interaction based diagnosis and cancer treatment and smart insulin delivery system.


FP-3:IL05  Targeted and Controlled Delivery of an Anti-tumor Chelator to Brain Cancer Cells
S. MAJD, University of Houston, Houston, TX, USA 

Current treatments for brain gliomas have limited success, making these tumors one of deadliest cancers. High sensitivity of malignant cells to iron deprivation has led to the application of chelators for cancer therapy. Effective application of such toxic compounds to brain tumors, however, requires their targeted delivery to minimize their toxicity towards healthy tissues. Here, we demonstrate that targeted and controlled delivery of a highly toxic chelator to glioma cells presents a promising strategy for defeating these neoplastic cells. A chelator, Dp44mT, that has shown tremendous anti-tumor activity in a number of other cancers, is packaged in biodegradable polymeric nanoparticles addressing brain glioma cells. This particle-based delivery proved effective in retaining the chelator's activity and toxicity towards glioma cells in both monolayer and spheroid cultures in vitro. Targeted particles carrying the chelator also reduced the tumor growth in nude mice model in vivo, without causing systematic toxicity or weight loss. In this talk, the formulation and evaluation of the chelator-carrying nanoparticles are presented.


Session FP-4 - Nanomaterials Systems for Bio-imaging and Theranostics

FP-4:IL01  Surface Modified Nanoparticles for Biomedical Imaging
PEILIN CHEN, Research Center for Applied Sciences, Academia Sinica, Taipei, Taiwan

In this lecture, we will discuss the development of various nanoparticles for in vivo imaging. We have utilized the multi-photon microscopy to investigate the disease models with the help of nanoparticles. We will discuss the enhanced permeability and retention (EPR) effect, which is a key feature of tumor blood vessels. In general, EPR-mediated passive targeting highly relies on the prolonged circulation time of nanocarriers. Particularly important two parameters, (1) nanocarrier size and (2) surface property are expected to play a key role on the pharmacokinetics and the biodistribution of the carrier material. Previously studies highlighted protein corona neutrality as an important design in the development of targeted nanomaterial delivery and demonstrated that a small difference in the surface heterogeneity could result in profoundly different interactions with cells and tissues. Therefore, the control and understanding of protein corona composition are critical for successful EPR-targeted nanomedicine. We will use mesoporous silica nanoparticles (MSNs) nanoparticles as an example to illustrate the effect of size and the surface heterogeneity of MSNs on their biological fate both in vitro and in vivo.


FP-4:IL03  Tumour Environment Responsive Oolymeric Nanomedicine for Multimodality Theranostics
ZHENGWEI MAO, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, China 

The development of smart theranostic systems with favorable biocompatibility, high loading efficiency, excellent circulation stability, potent anti-tumour activity, and multimodal diagnostic functionalities are of enormous importance for future clinical application. The premature burst release and poor degradation kinetics indicative of polymer-based nanomedicines remain to be the major obstacles for clinical translation, greatly reducing the maximum tolerated dose (MTD) and increasing toxicity towards normal tissues. Herein we report a novel approach for the preparation of theranostic shell crosslinked nanoparticles (SCNPs) based on a polyrotaxane constructed from host–guest complexation between a primary-amine containing β-cyclodextrin (β-CD-NH2) and a poly(ε-caprolactone) (PCL) segment. cRGDfk and perylene diimide (PDI) were chosen as the stoppers of the polyrotaxane, endowing the resultant SCNPs with excellent integrin targeting ability, photothermal effect, and photoacoustic capability. Activated by intracellular glutathione (GSH) activity, the sealed drugs were released controllably through photothermal effect, evidenced with a promising anti-tumor effect with a single-dose injection.


FP-4:IL04  Light-triggered Assembly of Gold Nanoparticles for Tumour Theranostics
XIAJU CHENG, HAIBIN SHI, Soochow University, Suzhou, Jiangsu, China

Gold nanoparticles (AuNPs) as potent theranostic agents have extensively been studied for photothermal therapy, radiosensitization, and photoacoustic (PA) imaging of cancers. However, spatiotemporally manipulating the aggregating behaviour remains lacking for effectively maximizing the photothermal efficacy, radiosensitization and imaging ability of small AuNPs in vivo. Herein, we for the first time demonstrated that AuNPs decorated with photolabile diazirine moieties could form covalently cross-linked aggregates upon laser irradiation (λ = 405 nm). Both in vitro and in vivo studies indicated that the light-triggered assembling remarkably shifted the surface plasmon resonance of Au particles to near-infrared regions and prolonged the residence time of AuNPs within tumors, which in consequence effectively enhanced the efficacy of photothermal therapy, radiosensitization, and sensitivity of photoacoustic imaging of tumours. We thus believe that the light-triggered crosslinking strategy may offer a valuable approach for improving the theranostic efficacies of functional NPs.


FP-4:L07  Rational Design of the Nano Bio Interface for Optimal Performance in Nanomedicine
I. YAROVSKY, P. CHARCHAR, N. TODOROVA, RMIT University, Melbourne Victoria, Australia

Nanomaterials are now widespread in biomedicine and engineering, yet their efficiency and safety remain a challenge. We employ theoretical modelling to facilitate rational engineering of nanomaterials with controlled biological responses. We develop atomic scale models providing in-depth understanding of fundamental interactions between engineered nanoparticles and the environment. Recent studies will be discussed in conjunction with challenges in modelling nano-bio interface with rigour and efficiency [1]. Examples include: (1) effects of nano-structuring on protein adsorption [2]; (2) effects of peptide surface density on the efficiency of peptide functionalised nanoparticles for drug delivery [3]; (3) effects of structure and dynamics of the functional epitope layer on the biosensing efficiency [4].
[1] P. Charchar, A. Christofferson, N. Todorova, I. Yarovsky, Small, 2016. [2] A. Hung, S. Mwenifumbo, M. Mager, J. Kuna, M. Hembury, F. Stellacci, I. Yarovsky, M. M. Stevens, J. Am. Chem. Soc. 133 2011 1438. [3] N.Todorova, C. Chiappini, M. Mager, B. Simona, Imran Patel, M. M. Stevens, I. Yarovsky, Nano Lett. 14 2014 5229. [4] H. Andersen, M. Mager, M. Griebner, P. Charchar, N. Todorova,N. Bell, G. Theocharidis, S. Bertazzo, I. Yarovsky, M.M. Stevens, Chem. Mater. 26 2014 4696

 
Session FP-5 - Clinical Translations in Diagnosis and Therapy, and in Implantable Prostheses and Micro-nano Devices

FP-5:IL01  Advanced Nanobiomaterials for Neural Interfaces
M.R. ABIDIAN, Biomedical Engineering, University of Houston, Houston, TX, USA

Recent advances in nanotechnology have generated wide interest in applying nanomaterials for neural prostheses. An ideal neural interface should create seamless integration into the nervous system and performs reliably for long periods of time. As a result, many nanoscale materials not originally developed for neural interfaces become attractive candidates to detect neural signals, stimulate neurons, and regenerate axons. I have extensive experience in application of polymeric nanobiomaterials for neural interface technology, particularly in the areas of neural recording, nerve regeneration, and drug delivery. I have a special interest in application of electroactive biomaterials for neural engineering and neural interfaces, in particular for neural tissue regeneration, drug delivery to brain tumor, and neurochemical sensing. In this talk, I will introduce some of the material-based approaches that we have developed within the past few years to improve long–term efficacy of neural interfaces. I will focus on synthesis, fabrication, and application of electroactive nanostructured materials including conducting polymer nanotubes and bioactive nanofibers for drug delivery to the brain, chronic neural recording, neurochemical sensing, and axonal regeneration.


FP-5:IL07  Nanoplasmonic Quantification of Tumor-derived Extracellular Vesicles in Plasma Microsamples for Diagnosis and Treatment Monitoring
K. LIANG, F. LIU, J. FAN, D. SUN, C. LIU, D.W. BERNARD, M.H. KATZ, E. J. KOAY, Z. ZHAO, TONY Y. HU, The Biodesign Institute, Arizona State University, Tempe, AZ, USA

Cancer-derived extracellular vesicles (EVs) are of increasing interest as a resource of diagnostic biomarkers. However, most EV assays are limited by large-sample needs, and are time-consuming, low-throughput and costly. Here, we describe a rapid, ultrasensitive and inexpensive nanoplasmon-enhanced scattering (nPES) assay that directly quantifies tumour-derived EVs from as little as 1 µL of unprocessed plasma. The assay uses the binding of antibody-conjugated gold nanospheres and nanorods to EVs captured by EV-specific antibodies on the surface of a sensor chip to produce a local plasmon effect that enhances tumour-derived EV detection sensitivity and specificity. We identified a pancreatic-cancer EV biomarker, ephrin type-A receptor 2 (EphA2), and demonstrate that the nPES assay for EphA2 EVs distinguishes pancreatic-cancer patients from pancreatitis patients and healthy subjects. EphA2 EVs were also informative in staging tumour progression and in detecting early responses to neoadjuvant therapy, with better performance than that of a conventional enzyme-linked immunosorbent assay. The nPES assay can be easily refined for clinical use, and be readily adapted for the diagnosis and monitoring of conditions with disease-specific EV biomarkers.