Functional reservoir microcapsules generated via microfluidic fabrication for long-term cardiovascular therapeutics

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

28 Scopus Citations
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Author(s)

  • Ngoc-Duy Dinh
  • Marek Kukumberg
  • Anh-Tuan Nguyen
  • Hamed Keramati
  • Song Guo
  • Dinh-Tuan Phan
  • Nurdiyana B. Ja'Afar
  • Erik Birgersson
  • Hwa Liang Leo
  • Ruby Yun-Ju Huang
  • Theodoros Kofidis
  • Abdul Jalil Rufaihah

Related Research Unit(s)

Detail(s)

Original languageEnglish
Pages (from-to)2756-2764
Journal / PublicationLab on a Chip
Volume20
Issue number15
Online published26 Jun 2020
Publication statusPublished - 7 Aug 2020

Abstract

Cardiovascular disease is a chronic disease that leads to impaired cardiac function and requires long-term management to control its progression. Despite the importance of hydrogels for therapeutic applications, a contradiction between the size of a hydrogel and the amount of loaded drug has been encountered when using conventional fabrication methods. In this study, biocompatible reservoir microcapsules (diameter ∼100 μm) with a large liquid core and polymeric shell were fabricated via a one-step phase separation of poly(ethylene glycol)diacrylate (PEGDA) and dextran within pre-gel droplets through microfluidics. By controlling the process of phase separation, high drug-loading efficiency (∼80%) for long-term release (30 days) of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) was achieved. Drug molecules were dispersed within the liquid core at a concentration above saturation solubility for sustained delivery via regulation of the shells. Effective therapeutic enhancement of human umbilical vein endothelial cell (HUVEC) and umbilical artery smooth muscle cell (SMC) proliferation and tube formation in vitro promoted rapid cell proliferation and increased the number of migrated cells by ∼1.7 times. Moreover, in vivo blood vessel regeneration for cardiovascular control induced by sustained dual-drug (VEGF and PDGF) delivery to the rat heart was achieved, showing the effectiveness of long-term protein delivery in improving cardiac function and significantly reducing ventricular wall thickness and fibrosis of the infarct region. The ratio of heart tissue scarring was reduced to 11.2% after microcapsule treatment compared with 21.4% after saline treatment in the rat model. By using these reservoir microcapsules, similar sustained delivery of proteins, mRNAs and biologic drugs could be developed for the treatment of a range of long-term chronic diseases and regenerative medicine.

Research Area(s)

  • ENDOTHELIAL GROWTH-FACTOR, AQUEOUS 2-PHASE SYSTEMS, SIMULTANEOUS ENCAPSULATION, MOLECULAR-MECHANISMS, DELIVERY, VEGF, ANGIOGENESIS, HYDROGELS, CARRIERS

Citation Format(s)

Functional reservoir microcapsules generated via microfluidic fabrication for long-term cardiovascular therapeutics. / Dinh, Ngoc-Duy; Kukumberg, Marek; Nguyen, Anh-Tuan et al.
In: Lab on a Chip, Vol. 20, No. 15, 07.08.2020, p. 2756-2764.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review