Electrospun zwitterionic nanofibers with in situ decelerated epithelialization property for non-adherent and easy removable wound dressing application

Unnithan, Afeesh Rajan,Ghavami Nejad, Amin,Sasikala, Arathyram Ramachandra Kurup,Thomas, Reju George,Jeong, Yong Yeon,Murugesan, Priya,Nasseri, Saeed,Wu, Dongmei,Park, Chan Hee,Kim, Cheol Sang Elsevier 2016 Chemical Engineering Journal Vol.287 No.-

<P><B>Abstract</B></P> <P>Wound care management is a serious issue among the medical practitioners due to its varying complexity and various materials were tested for fast relief and easy removal. In this regard zwitterionic polymer based wound dressing membranes are the key point of attraction. Here we prepared a novel zwitterionic poly (carboxybetaine-co-methyl methacrylate) (CBMA) copolymer based nanomembranes using the electrospinning technique for the wound dressing application. The study takes advantage of the outstanding chemical properties of zwitterionic CBMA and the morphological efficiency of nanomembranes. The cell attachment studies proved the cell inert nature of thus prepared membranes. Such non cell adherent wound dressing membranes can be applied as the easy removable, no-pain wound dressing bandages. Our results clearly showed that the excellent blood-inert nature can be achieved by the CBMA nanofiber membranes. Therefore, there will be less chance of attaching blood clot with the wound dressing membrane and is extremely significant for the care of patients with large areas of chronic wounds. Additionally the in vivo results showed the formation of new tissues within two weeks, evidence of a complete wound healing material. So our CBMA membrane can be successfully used as a perfect wound dressing material with minimum cosmetic scar.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Non cell adherent wound dressing membranes. </LI> <LI> Easy removable, no-pain wound dressing bandages. </LI> <LI> Blood inert wound dressing membrane, suitable for large areas of chronic wounds. </LI> <LI> Resist microbial biofilm formation and hence provides minimum chance of infection. </LI> <LI> Minimum cosmetic scar due to less cell adsorption on wound dressing membrane. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Mussel-Inspired Electrospun Nanofibers Functionalized with Size-Controlled Silver Nanoparticles for Wound Dressing Application

GhavamiNejad, Amin,Rajan Unnithan, Afeesh,Ramachandra Kurup Sasikala, Arathyram,Samarikhalaj, Melisa,Thomas, Reju George,Jeong, Yong Yeon,Nasseri, Saeed,Murugesan, Priya,Wu, Dongmei,Hee Park, Chan,Kim American Chemical Society 2015 ACS APPLIED MATERIALS & INTERFACES Vol.7 No.22

<P>Electrospun nanofibers that contain silver nanoparticles (AgNPs) have a strong antibacterial activity that is beneficial to wound healing. However, most of the literature available on the bactericidal effects of this material is based on the use of AgNPs with uncontrolled size, shape, surface properties, and degree of aggregation. In this study, we report the first versatile synthesis of novel catechol moieties presenting electrospun nanofibers functionalized with AgNPs through catechol redox chemistry. The synthetic strategy allows control of the size and amount of AgNPs on the surface of nanofibers with the minimum degree of aggregation. We also evaluated the rate of release of the AgNPs, the biocompatibility of the nanofibers, the antibacterial activity in vitro, and the wound healing capacity in vivo. Our results suggest that these silver-releasing nanofibers have great potential for use in wound healing applications.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/aamick/2015/aamick.2015.7.issue-22/acsami.5b02542/production/images/medium/am-2015-02542w_0005.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/am5b02542'>ACS Electronic Supporting Info</A></P>

Design and development of an electro magnetic manipulation system to actuate bioengineered magnetic micro/nanoparticles

Tumurbaatar Batgerel,Afeesh Rajan Unnithan,박찬희,김철생 대한기계학회 2018 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.32 No.4

This study introduces a new design of electromagnetic manipulation (EMM) system for wireless control of magnetic robots and magnetic nanoparticles for biomedical applications. It can generate a high-gradient magnetic field in the desired direction and forms the ponderomotive force distribution which allows the motion of magnetic robots in the specified direction. The real time microscopic-video supported by the LabVIEW vision system, the detection of object function through NI-Vision Assistant and tracking function through Math-Script node in the LabVIEW simulation. The motion speed and direction of the magnetic robotics/ nanoscale material can also be manipulated using EMM system and Joystick controller.

Rational design of bone extracellular matrix mimicking tri-layered composite nanofibers for bone tissue regeneration

Rezk, Abdelrahman I.,Rajan Unnithan, Afeesh,Hee Park, Chan,Sang Kim, Cheol Elsevier 2018 Chemical engineering journal Vol.350 No.-

<P><B>Abstract</B></P> <P>Multilayer nanofibrous scaffolds are gaining great attention in biomedical fields especially as tissue regeneration materials as well as drug delivery devices. Herein, we report the unique design of a tri-layered composite nanofiber scaffold mimicking the bone ECM for bone tissue regeneration. The tri-layered membrane consists of a superficial layer of PVA-PVAc loaded with simvastatin to initiate and improve osteogenesis process via sustained release of the drug as well as the excellent bioactivity of its blended polymers. The PCL-CA-β-tcp middle layer acts as a platform for stimulating the bio mineralization process mimicking the apatite like layer which mainly start after the first week of implantation. The final PCL layer performs as the fundamental layer to keep mechanical properties of the composite mat. The as prepared scaffolds were investigated in terms of morphology characterization, physiochemical properties, biomimetic mineralization, drug release and biocompatibility. The <I>in vitro</I> drug release study confirms the sustained release of simvastatin from the tri-layered membrane by obeying the Korsemeyer-Peppas, Higushi model and Kopcha model. The results demonstrate that the proposed biocompatible tri-layered scaffold will be a promising future material for bone tissue regeneration application by providing higher mineralization, enhanced cell attachment and proliferation.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Unique design of a tri-layered composite nanofiber scaffold mimicking the bone ECM. </LI> <LI> Single scaffold for bone regeneration and osteogenic drug delivery. </LI> <LI> Composite nanofiber enhanced osteoblast cell adhesion and proliferation. </LI> <LI> Potential platform for stimulating the biomineralization process. </LI> <LI> Drug release by obeying the Korsemeyer-Peppas and Kopcha model. </LI> </UL> </P>

Electrospun polyurethane/Eudragit^® L100-55 composite mats for the pH dependent release of paclitaxel on duodenal stent cover application

Aguilar, Ludwig Erik,Unnithan, Afeesh Rajan,Amarjargal, Altangerel,Tiwari, Arjun Prasad,Hong, Seong Tshool,Park, Chan Hee,Kim, Cheol Sang Elsevier 2015 International journal of pharmaceutics Vol.478 No.1

<P><B>Abstract</B></P> <P>A nanofiber composite mat of PU and Eudragit<SUP>®</SUP> L100-55 was created using electrospinning process. The pH dependent release of paclitaxel was successfully done with the use of PU/EL100-55 nanocomposite mats as the controlling platform. The morphology of the nanofiber composites was surveyed using FESEM and ratios of the polymers affects the diameter of the nanofiber. Characterization of the nanofiber composite mat was done using FTIR, DSC-TGA method. The release rate of paclitaxel was determined and analyzed by in vitro drug release method. In order to mimic the condition of a human duodenum, the fibers were submersed on PBS of different pH levels (4.0, 6.0,) respectively, and then analyzed using high performance liquid chromatography (HPLC). Composite mats submersed in PBS with pH 4.0 showed lesser release profile compared to mats submersed in PBS with pH of 6.0. The composite mat has adequate mechanical properties and in vitro cell biocompatibility indicating that the material can be used for drug eluting stent cover application.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Electromagnetic manipulation enabled calcium alginate Janus microsphere for targeted delivery of mesenchymal stem cells

Thomas, Reju George,Unnithan, Afeesh Rajan,Moon, Myeong Ju,Surendran, Suchithra Poilil,Batgerel, Tumurbaatar,Park, Chan Hee,Kim, Cheol Sang,Jeong, Yong Yeon Elsevier 2018 International journal of biological macromolecules Vol.110 No.-

<P><B>Abstract</B></P> <P>We prepared Janus microspheres based on sodium alginate for the encapsulation of mesenchymal stem cells (MSC) in one compartment and iron oxide nanoparticles (IONP) or a drug in the second compartment. 4% percent sodium alginate solution was allowed to pass through a septum-theta capillary device and react with 2.5% calcium chloride to allow crosslinking to occur in the solution, forming calcium alginate Janus microspheres. Physico-chemical characterization of microspheres was done by FTIR, TGA, and XRD after loading of stem cells and IONP/drug. The mechanical integrity of microspheres was tested at different time points, which showed that 4% alginate microspheres were mechanically stable for a long period of time. Live/dead staining of MSCs alone and the MTS assay of MSCs and DMSO co-loaded were performed, which showed less toxicity to MSC in the Janus configuration. IONP/MSC-loaded Janus microspheres were tested by magnetic manipulation for targeted MSC delivery for cartilage repair using an electromagnetic manipulation (EMM) device. Janus microspheres can be used for targeted stem cell/drug delivery using EMM for cartilage repair in the near future.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P> <P>Janus microsphere loaded with MSC’s and IONP/drug and injection to cartilage repair area.</P>

Real Time Monitoring of the Biocompatibility Behavior of Modified Titanium Oxide Surfaces Using Electrochemical Quartz Crystal Nanobalance (EQCN)

Kim, In Gi,Unnithan, Afeesh Rajan,Park, Chan Hee,Kim, Cheol Sang American Scientific Publishers 2017 Journal of Nanoscience and Nanotechnology Vol.17 No.6

<P>In this study, the biological interaction of a diversely modified three different Titanium (Ti) surfaces was analyzed using EQCN. EQCN was used to monitor the adhesion of bacteria on the Ti surfaces. The adherence of Escherichia coli and Staphylococcus aureus bacteria were continuously monitored by the changes in the resonant frequency (Delta f) of EQCN. The biocompatibilities of the surfaces were directly measured by correlating the attachment rate of bacteria on the surfaces. The results state that, among the surface modification techniques employed in the study, electrochemical adonization is a potential method to modify the material surfaces for biomedical application.</P>

Electrospun badger (Meles meles) oil/Ag nanoparticle based anti-bacterial mats for biomedical applications

김준희,김철상,박찬희,Afeesh Rajan Unnithan,kim han joo,Arjun Prasad Tiwari 한국공업화학회 2015 Journal of Industrial and Engineering Chemistry Vol.30 No.-

In this study, silver nanoparticles and badger oil were embedded into nanofibrous polyurethane (PU)mat via electrospinning. Badger oil is mainly composed of fatty acids and is used as a traditional medicine to heal wounds and the silver nanoparticles contribute to the wound healing process by reducing wound contamination. The composite mats exhibited good bactericidal activity against both of Gram positive and Gram negative bacteria. with better cell attachment and proliferation. The results of this study indicate that the proposed composite mats can be used for various biomedical purposes, including as dressing for burn wounds or to treat skin disease.

Design and application of a smart nanodevice by combining cationic drug delivery and hyperthermia for cancer apoptosis

Ramachandra Kurup Sasikala, Arathyram,Unnithan, Afeesh Rajan,Park, Chan Hee,Kim, Cheol Sang The Royal Society of Chemistry 2016 Journal of materials chemistry. B, Materials for b Vol.4 No.4

<P>Multifunctional magnetic nanoparticles have gained ample attention in the field of nanomedicine in recent years. Here, novel superparamagnetic core-shell manganese ferrite nanoparticles (MFNP)-encapsulated mesoporous silica nanoparticles (MSMFNPs) loaded with anticancer drug doxorubicin (DOX) for the combined application of hyperthermia and chemotherapy were developed and tested <I>in vitro</I>. Our results indicate that DOX-MSMFNPs achieved a favorable hyperthermic response in an alternating magnetic field in addition to cancer cell-specific cationic DOX release due to the cleavage of amide bonds under acidic pH, and synergistically contributed towards an enhanced tumoricidal effect.</P>

An implantable smart magnetic nanofiber device for endoscopic hyperthermia treatment and tumor-triggered controlled drug release

Sasikala, Arathyram Ramachandra Kurup,Unnithan, Afeesh Rajan,Yun, Yeo-Heung,Park, Chan Hee,Kim, Cheol Sang Elsevier 2016 ACTA BIOMATERIALIA Vol.31 No.-

<P><B>Abstract</B></P> <P>The study describes the design and synthesis of an implantable smart magnetic nanofiber device for endoscopic hyperthermia treatment and tumor-triggered controlled drug release. This device is achieved using a two-component smart nanofiber matrix from monodisperse iron oxide nanoparticles (IONPs) as well as bortezomib (BTZ), a chemotherapeutic drug. The IONP-incorporated nanofiber matrix was developed by electrospinning a biocompatible and bioresorbable polymer, poly (<SMALL>D</SMALL>,<SMALL>L</SMALL>-lactide-co-glycolide) (PLGA), and tumor-triggered anticancer drug delivery is realized by exploiting mussel-inspired surface functionalization using 2-(3,4-dihydroxyphenyl)ethylamine (dopamine) to conjugate the borate-containing BTZ anticancer drug through a catechol metal binding in a pH-sensitive manner. Thus, an implantable smart magnetic nanofiber device can be exploited to both apply hyperthermia with an alternating magnetic field (AMF) and to achieve cancer cell-specific drug release to enable synergistic cancer therapy. These results confirm that the BTZ-loaded mussel-inspired magnetic nanofiber matrix (BTZ-MMNF) is highly beneficial not only due to the higher therapeutic efficacy and low toxicity towards normal cells but also, as a result of the availability of magnetic nanoparticles for repeated hyperthermia application and tumor-triggered controlled drug release.</P> <P><B>Statement of Significance</B></P> <P>The current work report on the design and development of a smart nanoplatform responsive to a magnetic field to administer both hyperthermia and pH-dependent anticancer drug release for the synergistic anticancer treatment. The iron oxide nanoparticles (IONPs) incorporated nanofiber matrix was developed by electrospinning a biocompatible polymer, poly (<SMALL>D</SMALL>,<SMALL>L</SMALL>-lactide-co-glycolide) (PLGA), and tumor-triggered anticancer drug delivery is realized by surface functionalization using 2-(3,4-dihydroxyphenyl)ethylamine (dopamine) to conjugate the boratecontaining anticancer drug bortezomib through a catechol metal binding in a pH-sensitive manner. This implantable magnetic nanofiber device can be exploited to apply hyperthermia with an alternating magnetic field and to achieve cancer cell-specific drug release to enable synergistic cancer therapy, which results in an improvement in both quality of life and patient compliance.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>