김성수 (Harvard Medical School, 한국과학기술연구원) | 한빛사논문 > 한빛사

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조회346

김성수Seongsoo Kim

Harvard Medical School, 한국과학기술연구원

Adv. Mater., Oct 09 2024, | https://doi.org/10.1002/adma.202408488 Synergistic effect of Hypoxic Conditioning and Cell-Tethering Colloidal Gels enhanced Productivity of MSC Paracrine Factors and Accelerated Vessel Regeneration

Myung Chul Lee ^1,2, Jae Seo Lee ^1,3, Seongsoo Kim ^1,4, Anurag Jamaiyar ⁵, Winona Wu ^5,6, Montserrat Legorreta Gonzalez ¹, Tania Carolina Acevedo Durán ¹, Andrea Donaxi Madrigal-Salazar ¹, Nicole Bassous ¹, Violeta Carvalho ^1,7,8,9,10, Cholong Choi ¹, Da-Seul Kim¹, Jeong Wook Seo¹, Nelson Rodrigues ^7,11, Senhorinha F C F Teixeira ⁸, Abdulhameed F Alkhateeb ¹², Javier Alejandro Lozano Soto ¹, Mohammad Asif Hussain ¹², Jeroen Leijten ¹³, Mark W Feinberg ⁵, Su Ryon Shin ^1,9,10

¹Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02139, USA.

²Medicinal Materials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.

³Harvard Medical School and Wellman Center for Photomedicine, Massachusetts General Hospital, Cambridge, MA, 02139, USA.

⁴Biomaterials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.

⁵Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.

⁶Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston, MA, 02115, USA.

⁷MEtRICs, University of Minho, Campus de Azurém, Guimarães, 4800-058, Portugal.

⁸ALGORITMI/LASI Center, University of Minho, Campus de Azurém, Guimarães, 4800-058, Portugal.

⁹Center for MicroElectromechanical Systems (CMEMS-UMinho), University of Minho, Campus de Azurém, Guimarães, 4800-058, Portugal.

¹⁰LABBELS-Associate Laboratory, Braga/Guimarães, 4710-057, Portugal.

¹¹COMEGI-Center for Research in Organizations, Markets and Industrial Management, Lusíada Norte University, Porto, 1349-001, Portugal.

¹²Department of Electrical and Computer Engineering, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.

¹³Leijten Lab, Department of BioEngineering Technologies, Faculty of Science and Technology, Technical Medical Centre, University of Twente, Drienerlolaan 5, Enschede, 7522 NB, The Netherlands.

M.C.L, J.S.L., S.K., and A.J. contributed equally to this work as co-ﬁrstauthors.

Corresponding Authors: Mark W. Feinberg, Su Ryon Shin

Abstract

Microporous hydrogels have been widely used for delivering therapeutic cells. However, several critical issues, such as the lack of control over the harsh environment they are subjected to under pathological conditions and rapid egression of cells from the hydrogels, have produced limited therapeutic outcomes. To address these critical challenges, cell-tethering and hypoxic conditioning colloidal hydrogels containing mesenchymal stem cells (MSCs) are introduced to increase the productivity of paracrine factors locally and in a long-term manner. Cell-tethering colloidal hydrogels that are composed of tyramine-conjugated gelatin prevent cells from egressing through on-cell oxidative phenolic crosslinks while providing mechanical stimulation and interconnected microporous networks to allow for host-implant interactions. Oxygenating microparticles encapsulated in tyramine-conjugated colloidal microgels continuously generated oxygen for 2 weeks with rapid diffusion, resulting in maintaining a mild hypoxic condition while MSCs consumed oxygen under severe hypoxia. Synergistically, local retention of MSCs within the mild hypoxic-conditioned and mechanically robust colloidal hydrogels significantly increased the secretion of various angiogenic cytokines and chemokines. The oxygenating colloidal hydrogels induced anti-inflammatory responses, reduced cellular apoptosis, and promoted numerous large blood vessels in vivo. Finally, mice injected with the MSC-tethered oxygenating colloidal hydrogels significantly improved blood flow restoration and muscle regeneration in a hindlimb ischemia (HLI) model.

논문정보

형식Research article
게재일2024년 10월 (BRIC 등록일 2024-10-10)
연구진국내+국외 연구진
분야 바이오·의료융합 > 바이오소재

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