A Bioengineered Quercetin-Loaded 3D Bio-Polymeric Graft for Tissue Regeneration and Repair

Abstract

Phytochemicals extracted from plant sources have potential remedial effects to cure a broad range of acute to severe illnesses and ailments. Quercetin is a flavonoid isolated from different dietary sources such as vegetables and fruits, exhibiting strong anti-inflammatory, anti-oxidative and non-toxic effects on the biological system. However, the direct uptake or administration of quercetin results in loss of functionality, poor activity, and reduced shelf-life of the bioactive component. In this regard, to improve the uptake, potential, and efficiency of natural components with prolonged storage in the host's body after administration, numerous polymer drug delivery systems have been created. In the current study, three-dimensional (3D) porous (porosity: 92%; pore size: 81 µm) bio-polymeric foaming gelatin-alginate (GA) beads were fabricated for the entrapment of quercetin as therapeutic drug molecules-gelatin-alginate-quercetin (GAQ). The GAQ beads showed a significant uptake of quercetin molecules resulting in a reduction of reduced porosity up to 64% and pore size 63 µm with a controlled release profile in the PBS medium, showing ~80% release within 24 h. Subsequently, the GAQ beads showed remarkable antioxidant effects, and 95% anti-inflammatory activities along with remarkable in vitro cell culture growth and the observed proliferation of seeded fibroblast cells. Thus, we can conclude that the consistent release of quercetin showed non-toxic effects on normal cell lines and the bioactive surface of the GAQ beads enhances cell adhesion, proliferation, and differentiation more effectively than control GA polymeric beads and tissue culture plates (TCP). In summary, these findings show that these GAQ beads act as a biocompatible 3D construct with enormous potential in medicinal administration and tissue regeneration for accelerated healing.

Keywords: biocompatibility; drug; graft; herbal; quercetin; regeneration.

Figure 1

Schematic presentation of biogenic 3D polymeric foaming bead fabrication and quercetin-loaded hybrid beads with polymeric foaming stability curve showing significant foaming stability with time. Here, Green * labelling represents the foam stability curve of the polymeric blend indicates the stable foam generation of alginate-gelatin polymeric blend to bead fabrication and red * for quercetine solution for the modified alginate-gelatin bead formation.

Figure 2

The ultrastructure of polymeric beads- (A) Macroscopic examination (by Vernier caliper in millimeters), (B) microscopic FESEM images at 1 kX (scale bar 500 µm), and (C) FTIR spectra of all the controlled and modified beads samples, respectively.

Figure 3

Anti-inflammatory, anti-oxidative, and drug-release profile of the quercetin-loaded gelatin–alginate polymeric beads. Here * indicated the significant difference between the samples at p ≥ 0.05.

Figure 4

Fabricated polymeric beads’ biocompatibility study: MTT assay to check cell viability (A), and cell-seeded matrix FESEM images at 10 kX magnification (100 µm scale) (B) to show cell proliferation and adherence over the matrix (yellow arrows). Here * indicated the significant difference between the samples at p ≥ 0.05.