Controlled release of rhEGF and rhbFGF from electrospun scaffolds for skin regeneration

Abstract

Controlled delivery of multiple therapeutic agents can be considered as an effective approach in skin tissue engineering. In this study, recombinant human epidermal growth factor (rhEGF) and recombinant human basic fibroblast growth factor (rhbFGF) encapsulated in PLGA microspheres were loaded in hybrid scaffolds of PLGA and PEO. The scaffolds with various formulations were fabricated through electrospinning in order to maintain dual, individual or different release rate of rhEGF and rhbFGF. Morphological, physical and mechanical properties of the scaffold were investigated. The scaffold possessed uniform morphology with an average diameter of 280 nm for PLGA and 760 nm for PEO nanofibers. Furthermore, the mechanical properties of the scaffolds were shown to be akin to those of human skin. Bioactivity of the scaffolds for human skin fibroblasts was evaluated. The HSF acquired significant proliferation and well-spread morphology on the scaffolds particularly in the case of different release rate of rhEGF and rhbFGF which implies the synergistic effect of the growth factors. Additionally, collagen and elastin gene expression was significantly up-regulated in the HSF seeded on the scaffolds in the case of individual delivery of rhEGF and dual delivery of rhEGF and rhbFGF. In conclusion, the prepared scaffolds as a suitable supportive substrate and multiple growth factor delivery system can find extensive utilization in skin tissue engineering.

Future Prospects for Scaffolding Methods and Biomaterials in Skin Tissue Engineering: A Review

“…In the recent past, the use of various nanoparticle based microspheres, specifically PLGA, and natural polymers such as collagen or gelatin microspheres, has been reported for developing dermal or skin regeneration scaffolds for the effective delivery of drugs such as antibiotics or growth factors [177,178,179,180,181,182,183]. The size of microspheres in the scaffolds can be adjusted for the controlled release of proteins or drugs [177].…”

Nanofibrous Scaffolds for Skin Tissue Engineering and Wound Healing Based on Synthetic Polymers

“…In addition, these nanofibers reduced necrosis, improved vascularization, and maintained well-composed skin appendages in a mouse skin flap model in vivo [25]. Growth factors, namely recombinant human EGF and recombinant human basic fibroblast growth factor (bFGF), were also encapsulated in PLGA microspheres and loaded into hybrid scaffolds of PLGA and polyethylene oxide [90]. Both growth factors had a synergistic effect on the proliferation of human skin fibroblasts and increased the expression of genes for collagen and elastin in these cells [90].…”

“…Growth factors, namely recombinant human EGF and recombinant human basic fibroblast growth factor (bFGF), were also encapsulated in PLGA microspheres and loaded into hybrid scaffolds of PLGA and polyethylene oxide [90]. Both growth factors had a synergistic effect on the proliferation of human skin fibroblasts and increased the expression of genes for collagen and elastin in these cells [90]. Composite nanofibrous membranes containing PLGA and cellulose nanocrystals and loaded with neurotensin accelerated healing of full-thickness skin wounds in spontaneously diabetic mice [91].…”

“…For example, PEO was used to enable electrospinning of casein (i.e., a protein extensively used for drug delivery), which does not possess sufficient viscoelasticity due to its extensive intermolecular interactions [99], or to improve the electrospinnability and mechanical properties of silk fibroin [100]. As mentioned above, PEO or PEG was electrospun together with PMMA for creation of nanofibers delivering kynurenic acid [95] or with PLGA for delivery of human recombinant EGF and bFGF [90]. Other interesting applications of PEO include creation of electrospun carboxymethylcellulose/PEO nanofibers for delivery of viable commensal bacteria for preventive diabetic foot treatment [101], creation of three-dimensional scaffolds composed of PCL-PEG-PCL tri-block copolymer and iron oxide (Fe 3 O 4 ) nanoparticles for skin tissue engineering [102], creation of biodegradable nanofiber mats based on thermoresponsive multiblock poly(ester urethane)s comprising PEG, poly(propylene glycol) (PPG), and PCL, which showed improved hydrolytic degradation compared to pure PCL and excellent adhesion of human dermal fibroblasts [103].…”

<p>Antitumor Activity of Thermosensitive Hydrogels Packaging Gambogic Acid Nanoparticles and Tumor-Penetrating Peptide iRGD Against Gastric Cancer</p>

“…3 Polymers, such as hydrogels, possess the ability to reduce severe side effects of chemotherapeutic drugs and many of them are easy to operate and cause minimal trauma. [4][5][6][7] In recent years, silk fibroin hydrogels have been widely utilized in biomedical fields such as tissue regeneration and drug sustained release, owing to their good biocompatibility, thermal stability and controllable mechanical properties. [8][9][10] A kind of thermosensitive injectable hydrogel was prepared with hydroxypropyl cellulose (HPC) and silk fibroin (SF).…”