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Catalytic microgelators for decoupled control of gelation rate and rigidity of the biological gels

 Yu-Tong Hong  ;  Daniel T. Bregante  ;  Johnny Ching-Wei Lee  ;  Yongbeom Seo  ;  Dae-Hyun Kim  ;  Yong Jae Lee  ;  Lawrence B. Schook  ;  Hojeong Jeon  ;  Hak-Joon Sung  ;  David W. Flaherty  ;  Simon A. Rogers  ;  Hyunjoon Kong 
 JOURNAL OF CONTROLLED RELEASE, Vol.317 : 166-180, 2020 
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Fibrin gel ; MnO(2)nanosheets ; blood clotting ; hydrogen peroxide ; poly(lactic-co-glycolic acid) ; thrombin
Fibrin gels have been extensively used for three-dimensional cell culture, bleeding control, and molecular and cell therapies because the fibrous networks facilitate biomolecular and cell transport. However, a small window for gelation makes it difficult to handle the gels for desired preparation and transport. Several methods developed to control gelation rates often alter the microstructure, thereby affecting the mechanical response. We hypothesized that a particle designed to discharge thrombin cargos in response to an external stimulus, such as H2O2, would provide control of the gelation rate over a broad range while strengthening the gel. We examined this hypothesis by assembling poly (lactic-co-glycolic acid) (PLGA) particles loaded with thrombin and MnO2 nanosheets that decompose H2O2 to O2 gas. The resulting particles named as catalytic microgelator were mixed with fibrinogen solution or blood containing 0.2mM H2O2. Due to the increased internal pressure, these particles released a 3-fold larger mass of thrombin than PLGA particles loaded only with thrombin. As a consequence, catalytic microgelators increased the gelation time by one order of magnitude and the elastic modulus by a factor of two compared with the fibrin gel formed by directly mixing fibrinogen and thrombin in solution. These catalytic microgelators also served to clot blood, unlike PLGA particles loaded with thrombin. The resulting blood clot was also more rigid than the blood clot formed by thrombin solution. The results of this study would serve as a new paradigm in controlling gelation kinetics of pre-gel solution and mechanical properties of the post-gel matrix.
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1. College of Medicine (의과대학) > Dept. of Medical Engineering (의학공학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Dae-Hyun(김대현)
Sung, Hak-Joon(성학준) ORCID logo https://orcid.org/0000-0003-2312-2484
Lee, Yong Jae(이용재) ORCID logo https://orcid.org/0000-0003-0297-3116
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