Design and characterization of core-shell mPEG-PLGA composite microparticles for development of cell-scaffold constructs

TY - JOUR

T1 - Design and characterization of core-shell mPEG-PLGA composite microparticles for development of cell-scaffold constructs

AU - Wen, Yanhong

AU - Gallego, Monica Ramos

AU - Nielsen, Lene Feldskov

AU - Jorgensen, Lene

AU - Møller, Eva Horn

AU - Nielsen, Hanne Mørck

N1 - Copyright © 2013 Elsevier B.V. All rights reserved.

PY - 2013/9

Y1 - 2013/9

N2 - Appropriate scaffolds capable of providing suitable biological and structural guidance are of great importance to generate cell-scaffold constructs for cell-based tissue engineering. The aim of the present study was to develop composite microparticles with a structure to provide functionality as a combined drug delivery/scaffold system. Composite microparticles were produced by incorporating either alginate/dermatan sulfate (Alg/DS) or alginate/chitosan/dermatan sulfate (Alg/CS/DS) particles in mPEG-PLGA microparticles using coaxial ultrasonic atomization. The encapsulation and distribution of Alg/DS or Alg/CS/DS particles in the mPEG-PLGA microparticles were significantly dependent on the operating conditions, including the flow rate ratio (Qout/Qin) and the viscosity of the polymer solutions (Vout, Vin) between the outer and the inner feeding channels. The core-shell composite microparticles containing the Alg/DS particles or the Alg/CS/DS particles displayed 40% and 65% DS release in 10 days, respectively, as compared to the DS directly loaded microparticles showing 90% DS release during the same time interval. The release profiles of DS correlate with the cell proliferation of fibroblasts, i.e. more sustainable cell growth was induced by the DS released from the core-shell composite microparticles comprising Alg/CS/DS particles. After seeding fibroblasts onto the composite microparticles, excellent cell adhesion was observed, and a successful assembly of the cell-scaffold constructs was induced within 7 days. Therefore, the present study demonstrates a novel strategy for fabrication of core-shell composite microparticles comprising additional particulate drug carriers in the core, which provides controlled delivery of DS and favorable cell biocompatibility; an approach to potentially achieve cell-based tissue regeneration.

AB - Appropriate scaffolds capable of providing suitable biological and structural guidance are of great importance to generate cell-scaffold constructs for cell-based tissue engineering. The aim of the present study was to develop composite microparticles with a structure to provide functionality as a combined drug delivery/scaffold system. Composite microparticles were produced by incorporating either alginate/dermatan sulfate (Alg/DS) or alginate/chitosan/dermatan sulfate (Alg/CS/DS) particles in mPEG-PLGA microparticles using coaxial ultrasonic atomization. The encapsulation and distribution of Alg/DS or Alg/CS/DS particles in the mPEG-PLGA microparticles were significantly dependent on the operating conditions, including the flow rate ratio (Qout/Qin) and the viscosity of the polymer solutions (Vout, Vin) between the outer and the inner feeding channels. The core-shell composite microparticles containing the Alg/DS particles or the Alg/CS/DS particles displayed 40% and 65% DS release in 10 days, respectively, as compared to the DS directly loaded microparticles showing 90% DS release during the same time interval. The release profiles of DS correlate with the cell proliferation of fibroblasts, i.e. more sustainable cell growth was induced by the DS released from the core-shell composite microparticles comprising Alg/CS/DS particles. After seeding fibroblasts onto the composite microparticles, excellent cell adhesion was observed, and a successful assembly of the cell-scaffold constructs was induced within 7 days. Therefore, the present study demonstrates a novel strategy for fabrication of core-shell composite microparticles comprising additional particulate drug carriers in the core, which provides controlled delivery of DS and favorable cell biocompatibility; an approach to potentially achieve cell-based tissue regeneration.

KW - Alginates

KW - Anticoagulants

KW - Biocompatible Materials

KW - Cell Adhesion

KW - Cell Proliferation

KW - Cells, Cultured

KW - Chitosan

KW - Dermatan Sulfate

KW - Drug Compounding

KW - Drug Delivery Systems

KW - Fibroblasts

KW - Glucuronic Acid

KW - Guided Tissue Regeneration

KW - Hexuronic Acids

KW - Humans

KW - Materials Testing

KW - Microspheres

KW - Particle Size

KW - Polyesters

KW - Polyethylene Glycols

KW - Solubility

KW - Surface Properties

KW - Tissue Engineering

KW - Tissue Scaffolds

KW - Viscosity

U2 - 10.1016/j.ejpb.2013.03.027

DO - 10.1016/j.ejpb.2013.03.027

M3 - Journal article

C2 - 23958320

SN - 0939-6411

VL - 85

SP - 87

EP - 98

JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

IS - 1

ER -