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        Poly(ethylene glycol)-poly(lactic-co-glycolic acid) core-shell microspheres with enhanced controllability of drug encapsulation and release rate.

        Cha, Chaenyung,Jeong, Jae Hyun,Kong, Hyunjoon VSP 2015 Journal of Biomaterials Science. Polymer Edition Vol.26 No.13

        <P>Poly(lactic-co-glycolic acid) (PLGA) microspheres have been widely used as drug carriers for minimally invasive, local, and sustained drug delivery. However, their use is often plagued by limited controllability of encapsulation efficiency, initial burst, and release rate of drug molecules, which cause unsatisfactory outcomes and several side effects including inflammation. This study presents a new strategy of tuning the encapsulation efficiency and the release rate of protein drugs from a PLGA microsphere by filling the hollow core of the microsphere with poly(ethylene glycol) (PEG) hydrogels of varying cross-linking density. The PEG gel cores were prepared by inducing in situ cross-linking reactions of PEG monoacrylate solution within the PLGA microspheres. The resulting PEG-PLGA core-shell microspheres exhibited (1) increased encapsulation efficiency, (2) decreased initial burst, and (3) a more sustained release of protein drugs, as the cross-linking density of the PEG gel core was increased. In addition, implantation of PEG-PLGA core-shell microspheres encapsulated with vascular endothelial growth factor (VEGF) onto a chicken chorioallantoic membrane resulted in a significant increase in the number of new blood vessels at an implantation site, while minimizing inflammation. Overall, this strategy of introducing PEG gel into PLGA microspheres will be highly useful in tuning release rates and ultimately in improving the therapeutic efficacy of a wide array of protein drugs.</P>

      • SCISCIESCOPUS

        Microfluidics-Assisted Fabrication of Gelatin-Silica Core–Shell Microgels for Injectable Tissue Constructs

        Cha, Chaenyung,Oh, Jonghyun,Kim, Keekyoung,Qiu, Yiling,Joh, Maria,Shin, Su Ryon,Wang, Xin,Camci-Unal, Gulden,Wan, Kai-tak,Liao, Ronglih,Khademhosseini, Ali American Chemical Society 2014 Biomacromolecules Vol.15 No.1

        <P/><P>Microfabrication technology provides a highly versatile platform for engineering hydrogels used in biomedical applications with high-resolution control and injectability. Herein, we present a strategy of microfluidics-assisted fabrication photo-cross-linkable gelatin microgels, coupled with providing protective silica hydrogel layer on the microgel surface to ultimately generate gelatin-silica core–shell microgels for applications as in vitro cell culture platform and injectable tissue constructs. A microfluidic device having flow-focusing channel geometry was utilized to generate droplets containing methacrylated gelatin (GelMA), followed by a photo-cross-linking step to synthesize GelMA microgels. The size of the microgels could easily be controlled by varying the ratio of flow rates of aqueous and oil phases. Then, the GelMA microgels were used as in vitro cell culture platform to grow cardiac side population cells on the microgel surface. The cells readily adhered on the microgel surface and proliferated over time while maintaining high viability (∼90%). The cells on the microgels were also able to migrate to their surrounding area. In addition, the microgels eventually degraded over time. These results demonstrate that cell-seeded GelMA microgels have a great potential as injectable tissue constructs. Furthermore, we demonstrated that coating the cells on GelMA microgels with biocompatible and biodegradable silica hydrogels via sol–gel method provided significant protection against oxidative stress which is often encountered during and after injection into host tissues, and detrimental to the cells. Overall, the microfluidic approach to generate cell-adhesive microgel core, coupled with silica hydrogels as a protective shell, will be highly useful as a cell culture platform to generate a wide range of injectable tissue constructs.</P>

      • Structural Reinforcement of Cell-Laden Hydrogels with Microfabricated Three Dimensional Scaffolds.

        Cha, Chaenyung,Soman, Pranav,Zhu, Wei,Nikkhah, Mehdi,Camci-Unal, Gulden,Chen, Shaochen,Khademhosseini, Ali Royal Society of Chemistry 2014 Biomaterials Science Vol.2 No.5

        <P>Hydrogels commonly used in tissue engineering are mechanically soft, thus often display structural weakness. Herein, we introduce a strategy for enhancing the structural integrity and fracture toughness of cell-laden hydrogels by incorporating a three-dimensional (3D) microfabricated scaffold as a structural element. A digital micromirror device projection printing (DMD-PP) system, a rapid prototyping technology which employs a layer-by-layer stereolithographic approach, was utilized to efficiently fabricate 3D scaffolds made from photocrosslinkable poly(ethylene glycol) diacrylate (PEGDA). The scaffold was incorporated into a photocrosslinkable gelatin hydrogel by placing it in a pre-gel solution, and inducing in situ hydrogel formation. The resulting scaffold-reinforced hydrogels demonstrated significant increase in ultimate stress and provided structural support for weak hydrogels. In addition, the scaffold did not affect the rigidity of hydrogels, as it was not involved in the crosslinking reaction to form the hydrogel. Therefore, the presented approach could avoid inadvertent and undesired changes in the hydrogel rigidity which is a known regulator of cellular activities. Furthermore, the biocompatibility of scaffold-reinforced hydrogels was confirmed by evaluating the viability and proliferation of encapsulated fibroblasts. Overall, the strategy of incorporating 3D scaffolds into hydrogels as structural reinforcements presented in this study will be highly useful for enhancing the mechanical toughness of hydrogels for various tissue engineering applications.</P>

      • Multifunctional Heteroscaled Hydrogel Integrated with Dispersible Hybrid Nanofibers

        Chaenyung Cha(차채녕) 한국고분자학회 2021 한국고분자학회 학술대회 연구논문 초록집 Vol.46 No.2

        Hydrogels are widely used as scaffolds for cell and tissue culture applications. However, it is challenging to culture cells in 3D hydrogels at higher mechanical stiffness, as diminished permeability leads to limited diffusion of nutrients and available space for sufficient cellular activities. Herein, a novel strategy of incorporating short, aqueous-dispersible nanofibers into hydrogel is presented. Infusing nanofibers into hydrogel without changing the crosslinking density allowed the control of hydrogel mechanics, while limiting the change in permeability. Furthermore, nanofibers with a conductive polymer helped impart electrical conductivity to the hydrogel, allowing more efficient propagation of externally-applied electrical signals through the hydrogels. The resulting multifunctional nanofiber-infused hydrogels, with controllable mechanical and electrical properties, were utilized as a 3D cell culture platform to study the effects of various microenvironmental conditions.

      • KCI등재후보

        고분자와 세라믹의 만남 : 고분자를 통한 세라믹 3D 프린팅 기술의 발전

        차채녕(Chaenyung Cha) 한국세라믹학회 2020 세라미스트 Vol.23 No.1

        '스콜라' 이용 시 소속기관이 구독 중이 아닌 경우, 오후 4시부터 익일 오전 9시까지 원문보기가 가능합니다.

        The recent advances and popularity of 3D printing technology have centered around building polymerbased ‘plastic’ materials, due to their low cost, simple and efficient processing, and mechanical toughness. For this reason, printable polymers are actively recruited to create ‘ceramic resins’ that allow more facile fabrication of ceramic materials that are difficult to print directly. Herein, a brief history and the current state of ceramic 3D printing technology aided by polymer is summarized. In addition, a new ceramic 3D printing technology using polymer-derived ceramics (PDC) is also introduced.

      • SCISCIESCOPUS

        Integrative control of mechanical and degradation properties of in situ crosslinkable polyamine-based hydrogels for dual-mode drug release kinetics

        Kim, Mirae,Cha, Chaenyung Butterworth Scientific Ltd. etc. 2018 Polymer Vol.145 No.-

        <P><B>Abstract</B></P> <P>Michael addition is extensively utilized to fabricate hydrogels for biomedical applications, due their ability to undergo crosslinking reaction under physiological conditions without the need of a catalyst. Herein, mechanical properties and degradation behavior of in situ crosslinkable poly (ethylene glycol) diacrylate (PEGDA)-polyethyleneimine (PEI) hydrogels are explored. PEGDA and PEI, having acrylate and amine groups respectively, undergo crosslinking reaction via Michael addition to form hydrogels. The mechanical properties are controlled in a wide range by varying their concentrations and the molecular weight of PEGDA. In addition, the hydrogels are all shown to undergo degradation due to the expedited hydrolysis of ester linkages by the presence of unreacted amine groups on PEI. With this interesting combination of tunable mechanical properties and degradation, the PEGDA-PEI hydrogel system display a dual-mode drug release kinetics in which the drug release was governed by swelling-controlled and degradation-controlled mechanisms in sequence, which demonstrates the potential for drug delivery applications.</P> <P><B>Highlights</B></P> <P> <UL> <LI> In situ forming hydrogel via Michael addition between PEGDA and PEI is presented. </LI> <LI> Mechanical properties and degradation behavior are tuned by reactant parameters. </LI> <LI> Drug release kinetics are governed by “dual-mode” mechanisms. </LI> <LI> Swelling- and degradation-controlled drug release mechanisms occur in series. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

      • SCISCIESCOPUS

        Multivalent Polyaspartamide Cross-Linker for Engineering Cell-Responsive Hydrogels with Degradation Behavior and Tunable Physical Properties

        Jang, Jinhyeong,Cha, Chaenyung American Chemical Society 2018 Biomacromolecules Vol.19 No.2

        <P>Hydrogels possess favorable physical properties ideally suited for various biotechnology applications. To tailor to specific needs, a number of modification strategies have been employed to tune their properties. Herein, a multifunctional polymeric cross-linker based on polyaspartamide is developed, which allows for the facile adjustment of the type and number of reactive functional groups to fit different reaction schemes and control the physical properties of the hydrogels. The amine-based nucleophiles containing desired functional groups are reacted with polysuccinimide to synthesize polyaspartamide cross-linkers. The cross-linking density and the concurrent change in mechanical properties of the resulting hydrogels are controlled in a wide range only with the degree of substitution. This multivalency of the polyaspartamide linkers also induced the degradation of hydrogels by the unreacted functional groups on polyaspartamide involved in the hydrolysis. Furthermore, the polyaspartamide cross-linker conjugated with cell-recognition molecules via the same conjugation mechanism (i.e., nucleophilic substitution) render the hydrogels cell-responsive without the need of additional processing steps. This versatility of polyaspartamide-based cross-linker is expected to provide an efficient and versatile route to engineer hydrogels with controllable properties for biomedical applications.</P>

      • KCI등재

        Refined fabrication of mechano-stimulating micro-platform for on-chip analyses of complex platelet behavior

        김효재,Chulgyu Song,Chaenyung Cha,Jinmu Jung,Jonghyun Oh 한국공업화학회 2020 Journal of Industrial and Engineering Chemistry Vol.84 No.-

        Platelets can sense their surroundings as they crawl in search of optimal surface to adhere beforeactivation, but the detailed mechanism has not been fully explored in different microenvironments. Herein, various aspects of platelet behavior, including morphology, movement and biomarkerexpression, were multilaterally examined on mechanically stimulating surfaces, with controlled rigidityand roughness, to elucidate the effect of microenvironment without chemical stimulus. The plateletsdemonstrated different movement behavior (e.g. back-and-forth and forward crawling), and motility, aswell as varying degrees of spreading with lamellipodial andfilopodial projections, based on varyingmechanical microenvironments. Furthermore, after initial activation, the platelets all became stationaryand the cell spreading became more prominent, while still maintaining their movement potential. Pselectinexpression, along with α-granule and open canalicular system (OCS) distributions, all supportedthe morphological and movement behavior. These results strongly indicated that the mechanicalmicroenvironment played a key role in the regulation of complex platelet activities.

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