한빛사논문
- 조회378
Won-Kyu Rhim a,1, Jiwon Wooa,1, Jun Yong Kim a,b,c,1, Eun Hye Lee d, Seung-Gyu Cha a, Da-Seul Kim a, Seung-Woon Baek a,b,c, Chun Gwon Park b,c, Bum Soo Kim d,e, Tae Gyun Kwon d,e, Dong Keun Han a
aDepartment of Biomedical Science, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 13488, Republic of Korea
bDepartment of Biomedical Engineering and Intelligent Precision of Healthcare Convergence, SKKU Institute for Convergence, Sungkyunkwan University (SKKU) 2066 Seobu-ro, Jangan-gu, Suwon-si, Gyeonggi-do 16419, Republic of Korea
cIntelligent Precision of Healthcare Convergence, SKKU Institute for Convergence, Sungkyunkwan University (SKKU) 2066 Seobu-ro, Jangan-gu, Suwon-si, Gyeonggi-do 16419, Republic of Korea
dJoint Institute for Regenerative Medicine, Kyungpook National University, Jung-gu, Daegu 41944, Republic of Korea
eDepartment of Urology, School of Medicine, Kyungpook National University, Jung-gu, Daegu 41944, Republic of Korea
1These authors equally contributed to this work.
Corresponding author : Dong Keun Han
Abstract
Introduction: With prevalence of chronic kidney disease (CKD) in worldwide, the strategies to recover renal function via tissue regeneration could provide alternatives to kidney replacement therapies. However, due to relatively low reproducibility of renal basal cells and limited bioactivities of implanted biomaterials along with the high probability of substance-inducible inflammation and immunogenicity, kidney tissue regeneration could be challenging.
Objectives: To exclude various side effects from cell transplantations, in this study, we have induced extracellular vesicles (EVs) incorporated cell-free hybrid PMEZ scaffolds.
Methods: Hybrid PMEZ scaffolds incorporating essential bioactive components, such as ricinoleic acid grafted Mg(OH)2 (M), extracellular matrix (E), and alpha lipoic acid-conjugated ZnO (Z) based on biodegradable porous PLGA (P) platform was successfully manufactured. Consecutively, for functional improvements, melatonin-modulated extracellular vesicles (mEVs), derived from the human umbilical cord MSCs in chemically defined media without serum impurities, were also loaded onto PMEZ scaffolds to construct the multiplexed PMEZ/mEV scaffold.
Results: With functionalities of Mg(OH)2 and extracellular matrix-loaded PLGA scaffolds, the continuous nitric oxide-releasing property of modified ZnO and remarkably upregulated regenerative functionalities of mEVs showed significantly enhanced kidney regenerative activities. Based on these, the structural and functional restoration has been practically achieved in 5/6 nephrectomy mouse models that mimicked severe human CKD.
Conclusion: Our study has proved the combinatory bioactivities of the biodegradable PLGA-based multiplexed scaffold for kidney tissue regeneration in 5/6 nephrectomy mouse representing a severe CKD model. The optimal microenvironments for the morphogenetic formations of renal tissues and functional restorations have successfully achieved the combinatory bioactivities of remarkable components for PMEZ/mEV, which could be a promising therapeutic alternative for CKD treatment.
논문정보
- Research article
- 2024년 03월 (BRIC 등록일 2024-04-01)
- 국내 연구진
- 바이오·의료융합 > 바이오소재
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