Incorporation and release of dual growth factors for nerve tissue engineering using nanofibrous bicomponent scaffolds

Abstract

Electrospun fibrous scaffolds have been extensively used as cell-supporting matrices or delivery vehicles for various biomolecules in tissue engineering. Biodegradable scaffolds with tunable degradation behaviors are favorable for various resorbable tissue replacements. In nerve tissue engineering, delivery of growth factors (GFs) such as nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) from scaffolds can be used to promote peripheral nerve repair. In this study, using the established dual-source dual-power electrospinning technique, bicomponent scaffolds incorporated with NGF and GDNF were designed and demonstrated as a strategy to develop scaffolds providing dual GF delivery. NGF and GDNF were encapsulated in poly(D, L-lactic acid) (PDLLA) and poly(lactic-co-glycolic acid) (PLGA) nanofibers, respectively, via emulsion electrospinning. Bicomponent scaffolds with various mass ratios of GDNF/PLGA fibers to NGF/PDLLA fibers were fabricated. Their morphology, structure, properties, and the in vitro degradation were examined. Both types of core-shell structured fibers were evenly distributed in bicomponent scaffolds. Robust scaffolds with varying component ratios were fabricated with average fiber diameter ranging from 307 ± 100 nm to 688 ± 129 nm. The ultimate tensile stress and elastic modulus could be tuned ranging from 0.23 ± 0.07 MPa to 1.41 ± 0.23 MPa, 11.1 ± 3.0 MPa to 75.9 ± 3.3 MPa, respectively. Adjustable degradation was achieved and the weight loss of scaffolds ranged from 9.2% to 44.0% after 42 day degradation test. GDNF and NGF were incorporated with satisfactory encapsulation efficiency and their bioactivity were well preserved. Sustained release of both types of GFs was also achieved.

Coated electrospun alginate-containing fibers as novel delivery systems for regenerative purposes

“…It is well known that the hydrophobicity and then the degradation time of PLGA could be modulated by varying the lactide (L)-to-glycolide (G) ratio. 37,38 As for coated P1 fibers, several papers reported in literature confirm that ALG-based scaffolds, after cross-linking with bivalent ions, for example calcium ones, maintain their integrity, both in vitro and in vivo, up to 30 days. In particular, both ALG and Ca 2+ concentrations seem to play a pivotal role in determining scaffold degradation rate.…”

Evaluation of dual release of stromal cell‐derived factor‐1 and basic fibroblast growth factor with nerve conduit for peripheral nerve regeneration: An experimental study in mice

“…Other studies have concluded that the controlled combination release of the following bioactive molecules, bFGF, hepatocyte growth factor (HGF), keratinocyte growth factor (KGF), SDF‐1, and sphingosine‐1 phosphate agonist (SEW2871) have been effective for wound healing (Kim & Tabata, ; Ogino et al, ; Qu et al, ). In the peripheral nerve regeneration, the combination release of nerve growth factor (NGF) and glial cell‐derived neurotrophic factor, NGF and VEGF, and NGF and bFGF have also been reported in previous studies (Li et al, ; Liu et al, ; Xia & Lv, ). Recently, several types of nerve conduits have been clinically used for peripheral nerve regeneration; however, there is no nerve conduit aimed for the release of these bioactive molecules.…”

“…Recently, tissue engineering using the DDS, which promotes the activity of endogenous cells without exogeneous celltransplantation, has developed and many researchers have reported the usefulness of this system for tissue regenerations (Kimura & Tabata, ; Narita et al, ; Ohta et al, ; Tabata et al, ; Xu et al, ). In particular, since the development of drug delivery technology has allowed not only single release of bioactive molecules but dual release, the dual release of drugs using DDS has been increasingly remarkable and its robust effects have been demonstrated in many studies (Kim & Tabata, ; Kim & Tabata, ; Li et al, ; Liu et al, ; Ogino et al, ; Patel et al, ; Qu et al, ; Ratanavaraporn et al, ; Su et al, ; Xia & Lv, ; Zhang et al, ). In bone formation, the efficacy of dual release such as bone morphogenetic protein‐2 (BMP‐2) and vascular endothelial growth factor (VEGF), BMP‐2 and bFGF, BMP‐2 and SDF‐1, and BMP‐7 and SDF‐1 have been demonstrated in previous studies (Kim & Tabata, ; Patel et al, ; Ratanavaraporn et al, ; Su et al, ; Zhang et al, ).…”

“…In more recent years, the development of DDS has made it possible to release multiple biological molecules simultaneously. Dual release of bioactive molecules using DDS has been demonstrated to effectively promote tissue regeneration such as bone formation and wound healing as reported in many studies (Kim & Tabata, 2015Li et al, 2017;Liu et al, 2018;Ogino et al, 2018;Patel et al, 2008;Qu et al, 2018;Ratanavaraporn, Furuya, Kohara, & Tabata, 2011;Su, Xu, Sun, Gong, & Zhao, 2013;Xia & Lv, 2018;Zhang, Cheng, Miron, Shi, & Cheng, 2012). However, there has been a few reports about peripheral nerve regeneration using nerve conduit with dual controlled release of the bioactive molecules.…”

Core-shell nanofibers as drug delivery systems

“…Electrospinning of emulsions through a single nozzle (i.e., emulsion electrospinning) represents one of the ways to prepare core-shell fibers with successful incorporation of drugs, proteins and microspheres (4,15,20,22). For the two types of emulsions, oil-in-water (23) and water-in-oil (4,22,(24)(25)(26)(27), the use of water-in-oil emulsions has been more often reported in the literature. Water-in-oil emulsions frequently consist of an aqueous polymer solution with a dissolved hydrophilic drug or protein as the dispersed phase, with the continuous phase of a solution of hydrophobic polymer in an organic solvent, such as chloroform (4,27,28).…”