Three‐dimensional plotted alginate fibers embedded with diclofenac and bone cells coated with chitosan for bone regeneration during inflammation

Abstract

Alginate hydrogel fibers embedded with bone cells and diclofenac were coated with a layer of chitosan hydrogel and made into a porous scaffold by three-dimensional (3D) printing for drug release and bone regeneration. It was hypothesized that the chitosan coating could improve the scaffold's drug retention and release properties and biocompatibility. Macrophage cells were stimulated and cocultured with the scaffold. Tests were conducted to show how the chitosan coating affected the scaffold's drug release efficacy and how the release efficacy affected the cellular activities of stimulated macrophages and bone cells. The bone cells encapsulated in the coated scaffold demonstrated good viability after the acidic/basic coating process. The coating improved the retention and release efficacy of diclofenac and hence significantly inhibited interleukin-6 and tumor necrosis factor-α secretion from macrophages (p < 0.05). The bone cells in the coated sample mineralized more extensively than the control (p < 0.01). They also more actively expressed genes that produce proteins for extracellular matrix remodeling, MMP13, and interacting with the mineral matrix, OPN (both p < 0.01). It is believed that on days 7 and 10, when diclofenac was depleted and the concentrations of inflammatory compounds surged, the coating effectively blocked the harmful compounds and protected the bone cells within the fibers. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1511-1521, 2018.

Polysaccharide 3D Printing for Drug Delivery Applications

“…CS was used due to its mucoadhesive and pH-sensitive properties, in order to improve the controlled delivery of 5-FU at a pH value corresponding to the colonic environment. Similarly, a CS layer was coated on a 3D printed Alg scaffold loaded with diclofenac, an anti-inflammatory drug, aiming to retain more drug within the scaffold and slow down its diffusion during release [161]. An amount three times larger of diclofenac was loaded in the coated sample, demonstrating that the CS barrier could indeed prevent drug loss during scaffold preparation.…”

Advanced biomaterials for periodontal tissue regeneration

“…Composite membranes prepared using chitosan, polyvinyl alcohol, and hydroxyapatite containing meloxicam (a nonsteroidal anti‐inflammatory drug) demonstrated substantial anti‐inflammatory action, suggesting their potential use in periodontal therapy (Ngawhirunpat et al, 2009 ). Recently, bioprinted osteoblasts‐laden alginate‐based hydrogels containing diclofenac were used to manage inflammation and promote a healthy bone growth (Lin, Chang, & Peng, 2018 ). The printed system improves the scaffold's drug retention and release properties and biocompatibility.…”

“…The printed system improves the scaffold's drug retention and release properties and biocompatibility. While considerably reducing the inflammatory cytokine by macrophage, the bone cells establish their mineralization in a favorable microenvironment (Lin et al, 2018 ). Meanwhile, a novel immunomodulatory approach that targets periodontal tissue regeneration has recently been reported (Hu et al, 2018 ).…”

3D Printed Drug Delivery Systems Based on Natural Products

“…As well as in FDM, the drug is incorporated before extrusion [ 30 ]. In the last three years, the PAM technique has been employed in 8 studies with natural products to obtain drug delivery systems [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. These studies have been classified according to the nature of the natural product in 3D printed systems employing polysaccharides, proteins and lipids.…”

“…The controlled release properties of chitosan were also employed together with alginate to produce a tissue scaffold loaded with drug and cells employing natural polymers for the first time [ 32 ]. Alginates are natural polysaccharide polymers isolated from brown seaweed [ 40 ].…”