Hybrid 3D structure of poly(d,l-lactic acid) loaded with chitosan/chondroitin sulfate nanoparticles to be used as carriers for biomacromolecules in tissue engineering

Abstract

In the tissue engineering (TE) field, the concept of producing multifunctional scaffolds, capable not only of acting as templates for cell transplantation but also of delivering bioactive agents in a controlled manner, is an emerging strategy aimed to enhance tissue regeneration. In this work, a complex hybrid release system consisting in a three-dimensional (3D) structure based on poly(d,l-lactic acid) (PDLLA) impregnated with chitosan/chondroitin sulfate nanoparticles (NPs) was developed. The scaffolds were prepared by supercritical fluid foaming at 200 bar and 35 • C, and were then characterized by scanning electron microscopy (SEM) and micro-CT. SEM also allowed to assess the distribution of the NPs within the structure, showing that the particles could be found in different areas of the scaffold, indicating a homogeneous distribution within the 3D structure. Water uptake and weight loss measurements were also carried out and the results obtained demonstrated that weight loss was not significantly enhanced although the entrapment of the NPs in the 3D structure clearly enhances the swelling of the structure. Moreover, the hybrid porous biomaterial displayed adequate mechanical properties for cell adhesion and support. The possibility of using this scaffold as a multifunctional material was further evaluated by the incorporation of a model protein, bovine serum albumin (BSA), either directly into the PDLLA foam or in the NPs that were eventually included in the scaffold. The obtained results show that it is possible to achieve different release kinetics, suggesting that this system is a promising candidate for dual protein delivery system for TE applications.

Chondroitin sulphate: a focus on osteoarthritis

“…[126,127] Novel drug delivery systems of CS Polysaccharide based novel drug delivery systems have emerged with great success [97][98][99]. Over the past few years, plethora of novel drug delivery systems based on CS came into existence either as a ligand or a drug.…”

Chondroitin sulfate-based nanocarriers for drug/gene delivery

“…CS is a cationic polysaccharide which has been extensively investigated as a drug delivery vehicle owing to its special features of mucoadhesiveness, ease of chemical modification (Lee et al, 2008), and permeation-enhancing effect via temporarily opening the tight junctions between epithelial cells . Specially, in recent years, nanoparticles composed of ChS and CS have been successfully fabricated and evaluated (Hu, Chiang, & Po-da Hong, 2012;Santo, Duarte, Gomes, Mano, & Reis, 2010;Yeh, Cheng, Hu, Huang, & Young, 2011). Similarly, ChS-HA combined complex has been reported to be a plausible strategy in the field of drug/gene delivery (Zhang et al, 2011;Zhao, Gwon, Lim, Nho, & Kim, 2015).…”

Extremophilic polysaccharide nanoparticles for cancer nanotherapy and evaluation of antioxidant properties

“…MR/CH Nps were synthesized by polyelectrolyte complexation of CH and MR solutions under strong magnetic stirring [31]. Polyanionic molecules can interact with polycationic molecules via ionotrophic gelation for the formation of Nps [38]. Here, 3 mg of polyanionic MR was dissolved in 1 ml of ultra pure distilled water with pH 4.3, maintained using 0.1 N HCl.…”

“…Sulfated polysaccharides (SPS) are widely studied for their antiviral [5][6][7][8][9][10], anticancerous [5,7,11,12], anticoagulant [13,14], antiproliferating [12,13], and immunomodulating [5,7] properties, which makes them attractive for bionanoscience applications. Chitosan (CH) [15,16], heparin [17][18][19], chondroitin-6-sulfate [20][21][22], carrageenans [23][24][25][26], and fucoidans [27,28] are typical polysaccharides that are extensively used for formulating carrier matrix and stabilization of various Nps. It is evident that these materials are less cytotoxic and offers versatile material properties to polysaccharide-modified Nps [19].…”