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Huebsch, Nathaniel,Kearney, Cathal J.,Zhao, Xuanhe,Kim, Jaeyun,Cezar, Christine A.,Suo, Zhigang,Mooney, David J. National Academy of Sciences 2014 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.111 No.27
<P>Biological systems are exquisitely sensitive to the location and timing of physiologic cues and drugs. This spatiotemporal sensitivity presents opportunities for developing new therapeutic approaches. Polymer-based delivery systems are used extensively for attaining localized, sustained release of bioactive molecules. However, these devices typically are designed to achieve a constant rate of release. We hypothesized that it would be possible to create digital drug release, which could be accelerated and then switched back off, on demand, by applying ultrasound to disrupt ionically cross-linked hydrogels. We demonstrated that ultrasound does not permanently damage these materials but enables nearly digital release of small molecules, proteins, and condensed oligonucleotides. Parallel in vitro studies demonstrated that the concept of applying temporally short, high-dose “bursts” of drug exposure could be applied to enhance the toxicity of mitoxantrone toward breast cancer cells. We thus used the hydrogel system in vivo to treat xenograft tumors with mitoxantrone, and found that daily ultrasound-stimulated drug release substantially reduced tumor growth compared with sustained drug release alone. This approach of digital drug release likely will be applicable to a broad variety of polymers and bioactive molecules, and is a potentially useful tool for studying how the timing of factor delivery controls cell fate in vivo<I>.</I></P>
펨토초 레이저 가공을 이용한 3차원 약물 검사 시스템 구현
구상모(Sangmo Koo),Zhen Ma,Nathaniel Huebsch,Bruce R. Conklin,Costas P. Grigoropoulos,Kevin E. Healy 대한기계학회 2017 대한기계학회 춘추학술대회 Vol.2017 No.11
A human in vitro cardiac tissue model would help to understand the cardiovascular disease and develop new strategies for cardiac diseases such as arrhythmias. In this research, we developed in vitro a three-dimensional (3D) human artificial heart tissue by populating synthetic filamentous matrices using multi-photon absorption by the femtosecond laser. With this advanced fabrication method. two-photon polymerization, the bio-inspired cardiac tissue scaffold had fabricated with a cohort of 3D filamentous matrices that precisely regulated the structural alignment of cardiac tissue. By varying the mechanical properties such as thickness and stiffness of filamentous structure, different level of cardiomyocytes contractility abnormality and susceptibility to drug-induced cardiotoxicity were measured under different physical environments.
3차원 마이크로 파이버 플랫폼 구현을 통한 심장세포 수축력 변이 모델링
구상모(Sangmo Koo),Zhen Ma,Nathaniel Huebsch,Mohammad A. Mandegar,Brian Siemons,Steven Boggess,Bruce R. Conklin,Costas P. Grigoropoulos,Kevin E. Healy 대한기계학회 2018 대한기계학회 춘추학술대회 Vol.2018 No.12
The integration of 3D artificial fibrous platform by advanced laser-based direct writing (two-photon polymerization), and human induced pluripotent stem cells (hiPSCs) allows us to measure the physiolocal phenotypes and recapitulation of diverse cardiac diseases. And additional genome editing technologies also make it possible to mimic the realistic disease pathologies. Based on those techniques, it was possible to create the patient-customized 3D platform by fabricating the 3D microscale fibrous structure which has similar mechanical properties such as stiffness for cardiac disease research. 3D cardiac tissues are anchored between two flexible cantilevers, contraction (and relaxation) force was measured by measuring fiber deflection. It is served as force sensor, and showed the tissue mechanical resistance to contraction can regulated by external microenvironments.