Delivery of Dermatan Sulfate from Polyelectrolyte Complex-Containing Alginate Composite Microspheres for Tissue Regeneration

Abstract

Dermatan sulfate (DS) is a glycosaminoglycan (GAG) with a great potential as a new therapeutic agent in tissue engineering. The aim of the present study was to investigate the formation of polyelectrolyte complexes (PECs) between chitosan and dermatan sulfate (CS/DS) and delivery of DS from PEC-containing alginate/chitosan/dermatan sulfate (Alg/CS/DS) microspheres for application in tissue regeneration. The CS/DS complexes were initially formed at different conditions including varying CS/DS ratio (positive/negative charge ratio), buffer, and pH. The obtained CS/DS complexes exhibited stronger electrostatic interaction, smaller complex size, and more stable colloidal structure when chitosan was in large excess (CS/DS 3:1) and prepared at pH 3.5 as compared to pH 5 using acetate buffer. The CS/DS complexes were subsequently incorporated into an alginate matrix by spray drying to form Alg/CS/DS composite microspheres with a DS encapsulation efficiency of 90-95%. The excessive CS induced a higher level of sustained DS release into Tris buffer (pH 7.4) from the microspheres formulated at pH 3.5; however, the amount of CS did not have a significant effect on the release from the microspheres formulated at pH 5. Significant cell proliferation was stimulated by the DS released from the microspheres in vitro. The present results provide a promising drug delivery strategy using PECs for sustained release of DS from microspheres intended for site-specific drug delivery and ultimately for use in tissue engineering.

Engineering cartilage or endochondral bone: A comparison of different naturally derived hydrogels

“…A linear polysaccharide, chitosan consists of β (1→4) linked D-glucosamine residues with a variable number of randomly located N-acetylglucosamine groups and is structurally similar to a number of sGAGs and hyaluronic acids present in articular cartilage [44]. Furthermore, the cationic nature of chitosan facilitates the formation of ionic complexes with anionic polysaccharides such as sGAGs [45]. The chitosan hydrogel may therefore be supporting a favourable environment for the chondrogenesis of MSCs; firstly, by providing a structural framework containing cartilage specific biochemical cues, and secondly, by facilitating the development of a dense cartilaginous matrix through the entrapment of generated sGAGs, a mechanism which may be playing a further role in maintaining the chondrogenic phenotype.…”

Ultrasonic compatibilization of polyelectrolyte complex based on polysaccharides for biomedical applications

“…The main interactions between PEC include strong but reversible electrostatic and dipole-dipole association, as well as hydrogen and hydrophobic bonds [3]. Recently, numerous PEC have found application as carriers for drug delivery, enzyme immobilization, DNA binding, tissue engineering, biosensors, etc [4][5][6][7][8]. In all these cases it is important to notice that the stability of PEC could be affected by many factors including density of charges, degree of ionization, pH of reaction medium, concentration of polyelectrolytes, distribution of ionic groups, molecular weight, mixing ratio, order of reacting polyelectrolytes, and drying process [9].…”

In vivo bioactivity of rhBMP-2 delivered with novel polyelectrolyte complexation shells assembled on an alginate microbead core template

“…Polyelectrolyte complexes (PEC) formed by the electrostatic interactions of cations and anions have been attracting attention as "growth factor repositories" mainly because of the feasibility of tailoring their physicochemical properties and composition. For example: PEC microspheres, [1] membranes, [2] nanotubes, [3] nanoparticles, [4] fibers, [2] and coarcevates [5] have been developed based on different polysaccharides [4] and polyamines [6,7]. These have been used for core encapsulation [8], surface adsorption [9], and matrix entrapment [10] of different biomolecules and cells including, proteins, enzymes and stem cells [2,10,11].…”