Multidimensional nanofibrous hydrogels integrated triculture system for advanced myocardial regeneration

Dongwoo Kim; Yeong Hwan Kim; Gyubok Lee; Eun-Cheol Lee; Suk Ho Bhang; Kangwon Lee

doi:10.1088/1758-5090/ad9cc3

Multidimensional nanofibrous hydrogels integrated triculture system for advanced myocardial regeneration

Biofabrication. 2024 Dec 10. doi: 10.1088/1758-5090/ad9cc3. Online ahead of print.

Authors

Dongwoo Kim¹, Yeong Hwan Kim², Gyubok Lee³, Eun-Cheol Lee⁴, Suk Ho Bhang⁵, Kangwon Lee⁶

Affiliations

¹ Department of Applied Bioengineeirng, Seoul National University, Gwanak_1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Korea (the Republic of).
² Sungkyunkwan University, School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea, Jongno-gu, Seoul, 03063, Korea (the Republic of).
³ Seoul National University, Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea, Gwanak-gu, Seoul, 08826, Korea (the Republic of).
⁴ Sungkyunkwan University - Natural Sciences Campus, School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea, Suwon, Gyeonggi-do, 16419, Korea (the Republic of).
⁵ Sungkyunkwan University - Natural Sciences Campus, Seoburo 2066 RM 25419, Suwon 16419, Korea, Suwon, Gyeonggi-do, 16419, Korea (the Republic of).
⁶ Graduate School of Convergence Science and Technology, Seoul National University, Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea, Seoul, 08826, Korea (the Republic of).

PMID: 39657319
DOI: 10.1088/1758-5090/ad9cc3

Abstract

Myocardial infarction (MI) remains a leading cause of mortality worldwide, posing a significant challenge to healthcare systems. The limited regenerative capacity of cardiac tissue following MI results in chronic cardiac dysfunction, highlighting the urgent need for innovative therapeutic strategies. In this study, we explored the application of a multidimensional nanofibrous hydrogel for myocardial regeneration. We developed a composite hydrogel system by integrating fibrin, polycaprolactone (PCL), and alginate. In this system, fibrin supported cell proliferation and significantly enhanced angiogenesis when combined with human umbilical vein endothelial cells (HUVECs). PCL contributed to the alignment of encapsulated cells, improving their organization within the scaffold. Adipose-derived stem cells (ADSCs) were encapsulated within the hydrogel for their versatile regenerative potential, while C2C12 cells were incorporated for their ability to form muscle tissue. Additionally, the inclusion of alginate not only enhanced the mechanical properties of the hydrogel to better match the biomechanical demands of cardiac tissue but also played a critical role in reducing the immune response, thereby improving the system's biocompatibility. This study presents an advanced platform for myocardial regeneration using a nanofibrous hydrogel system designed to meet the dual requirements of mechanical robustness and cellular compatibility essential for cardiac tissue engineering. The triculture system, consisting of ADSCs, C2C12 cells, and HUVECs, harnesses the regenerative capabilities of each cell type, promoting both angiogenesis and tissue regeneration. This comprehensive approach addresses the immediate needs for cellular survival and integration while effectively overcoming long-term mechanical and immunological challenges.

Keywords: multidimensional nanofibrous hydrogel; myocardial regeneration; triculture system.