Conference Programme

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Overview
Session
BB-05: Hydrogels and other emerging therapeutics.
Time:
Tuesday, 20/Jun/2017:
4:00pm - 6:15pm

Session Chair: Kandalam V Ramanujachary, Rowan University
Location: Rm 328

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Presentations
4:00pm - 4:30pm
Invited

Self-Healing Mussel-Inspired Hydrogels

Henrik BIRKEDAL

Department of Chemistry & iNANO, Aarhus University, Denmark

Self-healing materials are currently of intense interest. Self-healing materials are known from several biological materials including the blue mussel byssus that together with plant polyphenols have inspired researchers to make such smart materials by employing catechols or catechol analogues [1]. Catechols can coordinate metal ions reversibly making them ideal candidates for rapid self-healing. They in many cases also spontaneously undergo covalent cross-linking under mildly basic conditions, which has spurned the widespread use of polydopamine in biomaterials research.

The blue mussel foot proteins contain both catechols and amines and we showed how combining these features in a bioinspired hydrogel material enables forming stimuli-responsive hydrogels with a strongly pH-dependent stiffness [2, 3]. This was achieved by grafting DOPA onto poly-amines and then forming hydrogels through the pH-dependent coordination to hard metal ions such as Fe(III) or Al(III). Supramolecular self-healing hydrogels can be formed by employing tannic acid/metal ion coordination polymers and polyamines. The hydrogels become covalently reinforced into double crosslinked hydrogels above pH~8 due to the formation of covalent crosslinks between the polyphenol and the polyamine [4]. I will show how we can control materials properties in detail e.g. by incorporating self-healing through oxidation resistant catechol analogues and then dialing stiffness through covalent crosslinks induced by addition of e.g. polyphenols. This provides double crosslink self-healing hydrogels with controllable properties. This type of materials provides a diverse platform for forming self-healing and stimuli responsive materials.

References:

[1] Krogsgaard M, Nue V, & Birkedal H (2016) Chem. Eur. J. 22:844–857.

[2] Krogsgaard M, Hansen MR, & Birkedal H (2014) J. Mater. Chem. B 2:8292-8297.

[3] Krogsgaard M, Behrens MA, Pedersen JS, & Birkedal H (2013) Biomacromolecules 14(2):297-301.

[4] Krogsgaard M, Andersen A, & Birkedal H (2014) Chem. Commun. 50:13278-13281.


4:30pm - 5:00pm
Invited

Systematic Access to N,N-Containing Heterocycles: Drug Discovery by Overlapping Chemical Space with Biological Space

Gustavo MOURA-LETTS

Rowan University, United States

N,N-Containing heterocycles are among the most important families of pharmacologically relevant molecular scaffolds. Their properties extend from anti-inflammatory to anti-microbial, analgesic, anti-viral, anti-fungal, analgesic, anti-psychotic, anxiolytic, and anti-histaminic. Among these: pyrazolines, diazepines, benzodiazepines are especially relevant due to their sedative, hypnotic, anxiolytic, anti-convulsing and muscle relaxant properties. We have developed a novel and systematic approach for the synthesis of these N,Ncontaining heterocycles scaffolds from simple, accessible diaziridines.


5:00pm - 5:15pm
Oral

An Antithrombotic Hydrogel with Thrombin-responsive Fibrinolytic Activity

Hui DU, Cong LI, Dan LI, Hong CHEN

Soochow University, China

Foreign material surface-induced thrombosis remains the major cause of failure of implanted blood contacting medical devices despite intensive research over several decades. The incorporation of bioactive agents capable of inhibiting thrombosis is one of the main strategies for the development of antithrombotic biomaterials. However, the presence of antithrombotic agents may lead to disorders of the hemostatic system and other unfavorable effects in the normal blood environment. Herein, a novel concept of a thrombolytic material whose activity is triggered by the generation of a clot/thrombus is developed. The concept is realized using a tissue plasminogen activator (t-PA)-loaded hydrogel crosslinked by a thrombin-cleavable peptide. The hydrogel was shown to degrade and release t-PA in serum only when thrombin (generated in clot formation) was present. The rates of hydrogel degradation and t-PA release could be adjusted by changing the degree of crosslinking of the hydrogel. t-PA release was also found to be dependent on the thrombin concentration and could be controlled in an ‘‘on–off’’ manner depending on the presence and absence, respectively, of thrombin. Importantly, the hydrogel was able to lyse fibrin specifically in the presence of thrombin, suggesting thrombosis-responsive fibrinolytic properties. The t-PA loaded hydrogel developed therefore has potential for use as a coating in blood contacting devices.


5:15pm - 5:30pm
Oral

Tracing and Inhibiting of Tumor Metastasis through Blood Vascular System with Ultrasmall Nanoparticals by Theranostic Nanoplatforms

Yu JI, QuLi FAN

Nanjing University of Posts and Telecommunications, China

The metastatic spread of tumor cells is increasing the risk of cancer recurrence directly or indirectly, demoting prognosis and quality of life of more than 90% patients. Sentinel node is defined as the first lymph node to receive cancer cell drainage from the primary tumor, the lymph node to which cancer cells metastasize initially. So it is important for us to identify the location of sentinel lymph nodes, remove those nodes using sentinel lymph node (SLN) excision method which invaded by metastatic tumor cells. Although effective, SLN excision is an invasive procedure requiring radioactive tracing. In addition, diminutive tumor growth adjacent non-renewable nerves or around vital organ function is difficult to cut through surgery. Therefore, a probe can accurate imaging and timely ablation which integrated diagnosis and treatment of small lesions has important clinical significance.

In this work, melanin as an efficient endogenous nanosystem for imaging-guided noninvaded photothermal therapy that affords effective destruction of primary tumors and cancer cells in sentinel lymph nodes, thus inhibiting tumor metastasis in a mouse tumor model. Our results demonstrated that MNPs can selectively accumulated in lymph node metastasis compared to the normal tissue through the extravasation from the blood vascular. At the same time, the PA signal intensity and retention time of MNPs in the lymph node are superior to the properties of ICG.Our results precisely validate this fact that lymphatic can be clearly seen while imaging the SLN and primary tumor and achieve high cure rate in our mouse tumor model. We called this 1+1﹥2 effects.

This work demonstrates novel, nanotechnology-based therapy and imaging approaches to tumor metastasis inhibition.


5:30pm - 5:45pm
Oral

The Analysis of Inhomogeneous Swelling of Gels Using A New Interpolating Meshless Method

Yajie DENG, Xiaoqiao HE

City University of Hong Kong, Hong Kong S.A.R. (China)

The swelling deformation of polymer gel under the stimuli of solvent can be controlled based on different mechanical loads and geometric constraints. Due to these properties, the polymer gel can be used as actuators to achieve expected deformations and motions.

In this paper, the Flory-Rehner free energy function and a multiplication decomposition of deformation gradient are introduced to build the governing equation of two-dimensional inhomogeneous swelling large deformation of polymer gel. Then a new interpolating meshless method is used to simulate the deformation process of polymer gel. The meshless method which is independent of mesh can avoid the mesh distortion in computing process, so compared with the finite element method the meshless method is more suitable to research the large deformation of polymer gel.

Several examples are analyzed to validate the applicability of the new interpolating meshless method for two-dimensional inhomogeneous swelling of polymer gel. And by designing different geometric pattern lattice, the buckling of actuators can produce different rotary motions to obtain controlled motions under geometric constraints and external solvents. The deformation trends simulated by the new meshless method agree well with existing experimental results.


5:45pm - 6:00pm
Oral

Design and Evaluation of Betulin-Based Anti-Cancer Compounds

Anjali CHAKRADHAR

High Technology High School, United States

Betulin is a natural compound present in the bark of birch trees, which are abundant in North America. Betulin has been shown and recognized by the National Cancer Institute as having promising anti-cancer effects. However, there are no betulin-based anti-cancer drugs today due to betulin’s poor solubility in aqueous media like blood serum and lack of effective activity against cancer cell lines in low (nM) concentrations. This project modifies the molecular structure of betulin-derivatives to increase their effectiveness against cancer cells. Betulin was extracted from birch bark by using a series of organic solvents and a compound called betulinic acid was synthesized. To improve bioavailability, the molecular structure of betulinic acid was modified to realize different anti-cancer compounds. Specifically, betulinic acid was combined with several different amines to synthesize different analogs. The potency of the three anti-cancer compounds was evaluated in-vitro on cell-lines for prostate cancer. The IC50 values showed that the betulin analogs are effective on cancer cells in the micro-molar concentrations. However, most commercial anti-cancer drugs are effective in nano-molar concentrations. The next steps would be to synthesize betulin-salts from the analogs to further increase solubility, and to add other active agents to the betulin molecule to further improve effectiveness.


6:00pm - 6:15pm
Oral

Convergence of Biology and Electronics- Bioelectronics via 3D Printing

Shweta AGARWALA

Nanyang Technological University, Singapore

Bringing together electronics and biology on single platforms can pave for highly sensitive and novel biomedical devices and clinical applications. Advances in materials, manufacturing and electronics has fueled research on platforms where all three can be combined for smart and novel applications. This field is fueled by innovations in electronics, biotechnology and has received a strong boost with the advent of 3D bioprinting technique. 3D printing is driving the bio-medical industry with specifications such as user customization, cost-effectiveness and short response time. Here I discuss our work that leverages on 3D printing techniques for tissue engineering and biocompatible biomedical platforms. We report printing, optimization and characterization of electronic tracks on bio-scaffolds for making complete devices to understand printing capability on such platforms. The fabricated devices and electronics are compatible with cells and tissues, cheap and do not require any post-processing.



 
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