Development of Injectable Amniotic Membrane Matrix for Postmyocardial Infarction Tissue Repair - PubMed (original) (raw)

. 2020 Jan;9(2):e1900544.

doi: 10.1002/adhm.201900544. Epub 2019 Nov 28.

Lawrence Delrosario 2, Jun Fang 3, Sze Yue Wong 1, Qizhi Fang 2, Richard Sievers 2, Surya Kotha 1, Aijun Wang 4, Diana Farmer 4, Praneeth Janaswamy 2, Randall J Lee 2, Song Li 1 3

Affiliations

Development of Injectable Amniotic Membrane Matrix for Postmyocardial Infarction Tissue Repair

Jeffrey J D Henry et al. Adv Healthc Mater. 2020 Jan.

Abstract

Ischemic heart disease represents the leading cause of death worldwide. Heart failure following myocardial infarction (MI) is associated with severe fibrosis formation and cardiac remodeling. Recently, injectable hydrogels have emerged as a promising approach to repair the infarcted heart and improve heart function through minimally invasive administration. Here, a novel injectable human amniotic membrane (hAM) matrix is developed to enhance cardiac regeneration following MI. Human amniotic membrane is isolated from human placenta and engineered to be a thermoresponsive, injectable gel around body temperature. Ultrasound-guided injection of hAM matrix into rat MI hearts significantly improves cardiac contractility, as measured by ejection fraction (EF), and decrease fibrosis. The results of this study demonstrate the feasibility of engineering as an injectable hAM matrix and its efficacy in attenuating degenerative changes in cardiac function following MI, which may have broad applications in tissue regeneration.

Keywords: amniotic membranes; decellularization; hydrogels; myocardial infarctions.

© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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Figures

Figure 1.

Figure 1.. Physical appearance of hAM matrix during various stage of processing.

(A) Untreated hAM prior to decellularization. (B) Decellularized hAM tissue. (C) Lyophilized and ground soluble hAM matrix. (D) Gelation of decellularized hAM matrix at 37 °C. (E) Rheological measurement for storage modulus of hAM matrix between oscillatory frequencies 10 and 0.1 Hz at 1% strain amplitude. Data presented as a mean of 5 separate measurements ± one standard deviation.

Figure 2.

Figure 2.. Histological and biochemical characterization of CHAPS and SDS decellularized hAM tissue.

(A-C) Representative H&E staining images of untreated, CHAPS decellularized and SDS decellularized hAM. (D-F) DAPI staining of nuclei present in untreated, CHAPS decellularized, and SDS decellularized hAM. (G) Percentage of DNA content remaining after CHAPS or SDS decellularization. (H) Percentage of glycosoaminoglycan (GAG) content remaining after CHAPS or SDS decellularization. (I) Percentage of collagen content remaining after CHAPS or SDS decellularization.

Figure 3:

Figure 3:. Proliferation, biocompatibility, viability of bovine aortic endothelial cells on hAM matrix.

BAECs were seeded at low (1000 cells/cm2), medium (5000 cells/cm2), and high density (10,000 cells/cm2) on either hAM matrix or collagen-1. Proliferation was measured using EdU (A) and is presented as the percentage of total DAPI stained cells expressing positive EdU staining (B). (C) Live/dead staining of ECs at days 2 and 6. Cells were seeded at 5000 cells/cm2. (D) Cell viability assay at days 2 and 6. Cells were seeded at 5000 cells/cm2.

Figure 4:

Figure 4:. Effect of hAM matrix injection on LV ejection fraction (LVEF) and LV fractional shortening (LVFS) after 5 weeks following acute MI.

(A) Average LVEF before and after injection of PBS or hAM matrix, labeled as pre-treatment (Pre) or post-treatment (Post) respectively. (B) LVEF of each animal before and after injection of PBS or hAM matrix. (C) Average of LVEF changes by using pre-treatment value of each animal as a reference. (D) Average of LVFS changes by using pre-treatment value in each animal as a reference. n = 5 for each group, * p < 0.05.

Figure 5.

Figure 5.. hAM matrix promotes adult cardiac regeneration after MI.

(A) Representative images of Masson trichrome-stained heart sections at 5 weeks after hAM matrix or PBS injection. Scale bars represent 4 mm. (B) Measurement of infarcted size at 5 weeks after hAM matrix or PBS injection analyzed by Masson trichrome staining. n = 5 for each group, * p < 0.05.

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