Browsing by Author "Lee, Sang Jin"

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    3D Bioprinted Human Skeletal Muscle Constructs for Muscle Function Restoration
    Kim, Ji Hyun; Seol, Young-Joon; Ko, In Kap; Kang, Hyun-Wook; Lee, Young Koo; Yoo, James J.; Atala, Anthony; Lee, Sang Jin (Springer Nature, 2018-08-17)
    A bioengineered skeletal muscle tissue as an alternative for autologous tissue flaps, which mimics the structural and functional characteristics of the native tissue, is needed for reconstructive surgery. Rapid progress in the cell-based tissue engineering principle has enabled in vitro creation of cellularized muscle-like constructs; however, the current fabrication methods are still limited to build a three-dimensional (3D) muscle construct with a highly viable, organized cellular structure with the potential for a future human trial. Here, we applied 3D bioprinting strategy to fabricate an implantable, bioengineered skeletal muscle tissue composed of human primary muscle progenitor cells (hMPCs). The bioprinted skeletal muscle tissue showed a highly organized multi-layered muscle bundle made by viable, densely packed, and aligned myofiber-like structures. Our in vivo study presented that the bioprinted muscle constructs reached 82% of functional recovery in a rodent model of tibialis anterior (TA) muscle defect at 8 weeks of post-implantation. In addition, histological and immunohistological examinations indicated that the bioprinted muscle constructs were well integrated with host vascular and neural networks. We demonstrated the potential of the use of the 3D bioprinted skeletal muscle with a spatially organized structure that can reconstruct the extensive muscle defects.
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    Dynamic, Nondestructive Imaging of a Bioengineered Vascular Graft Endothelium
    Whited, Bryce M.; Hofmann, Matthias C.; Lu, Peng; Xu, Yong; Rylander, Christopher G.; Wang, Ge; Sapoznik, Etai; Criswell, Tracy; Lee, Sang Jin; Soker, Shay; Rylander, M. Nichole (PLOS, 2013-04-09)
    Bioengineering of vascular grafts holds great potential to address the shortcomings associated with autologous and conventional synthetic vascular grafts used for small diameter grafting procedures. Lumen endothelialization of bioengineered vascular grafts is essential to provide an antithrombogenic graft surface to ensure long-term patency after implantation. Conventional methods used to assess endothelialization in vitro typically involve periodic harvesting of the graft for histological sectioning and staining of the lumen. Endpoint testing methods such as these are effective but do not provide real-time information of endothelial cells in their intact microenvironment, rather only a single time point measurement of endothelium development. Therefore, nondestructive methods are needed to provide dynamic information of graft endothelialization and endothelium maturation in vitro. To address this need, we have developed a nondestructive fiber optic based (FOB) imaging method that is capable of dynamic assessment of graft endothelialization without disturbing the graft housed in a bioreactor. In this study we demonstrate the capability of the FOB imaging method to quantify electrospun vascular graft endothelialization, EC detachment, and apoptosis in a nondestructive manner. The electrospun scaffold fiber diameter of the graft lumen was systematically varied and the FOB imaging system was used to noninvasively quantify the affect of topography on graft endothelialization over a 7-day period. Additionally, results demonstrated that the FOB imaging method had a greater imaging penetration depth than that of two-photon microscopy. This imaging method is a powerful tool to optimize vascular grafts and bioreactor conditions in vitro, and can be further adapted to monitor endothelium maturation and response to fluid flow bioreactor preconditioning.
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    Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform
    Skardal, Aleksander; Murphy, Sean V.; Devarasetty, Mahesh; Mead, Ivy; Kang, Hyun-Wook; Seol, Young-Joon; Zhang, Yu Shrike; Shin, Su-Ryon; Zhao, Liang; Aleman, Julio; Hall, Adam R.; Shupe, Thomas D.; Kleensang, Andre; Dokmeci, Mehmet R.; Lee, Sang Jin; Jackson, John D.; Yoo, James J.; Hartung, Thomas; Khademhosseini, Ali; Soker, Shay; Bishop, Colin E.; Atala, Anthony (Springer Nature, 2017-08-18)
    Many drugs have progressed through preclinical and clinical trials and have been available - for years in some cases -before being recalled by the FDA for unanticipated toxicity in humans. One reason for such poor translation from drug candidate to successful use is a lack of model systems that accurately recapitulate normal tissue function of human organs and their response to drug compounds. Moreover, tissues in the body do not exist in isolation, but reside in a highly integrated and dynamically interactive environment, in which actions in one tissue can affect other downstream tissues. Few engineered model systems, including the growing variety of organoid and organ-on-a-chip platforms, have so far reflected the interactive nature of the human body. To address this challenge, we have developed an assortment of bioengineered tissue organoids and tissue constructs that are integrated in a closed circulatory perfusion system, facilitating inter-organ responses. We describe a three-tissue organ-on-a-chip system, comprised of liver, heart, and lung, and highlight examples of inter-organ responses to drug administration. We observe drug responses that depend on inter-tissue interaction, illustrating the value of multiple tissue integration for in vitro study of both the efficacy of and side effects associated with candidate drugs.