G‐CSF loaded nanofiber/nanoparticle composite coated with collagen promotes wound healing in vivo

Abstract

Sustained release of functional growth factors can be considered as a beneficial methodology for wound healing. In this study, recombinant human granulocyte colony-stimulating factor (G-CSF)-loaded chitosan nanoparticles were incorporated in Poly(ε-caprolactone) (PCL) nanofibers, followed by surface coating with collagen type I. Physical and mechanical properties of the PCL nanofibers containing G-CSF loaded chitosan nanoparticles PCL/NP(G-CSF) and in vivo performance for wound healing were investigated. G-CSF structural stability was evaluated through SDS_PAGE, reversed phase (RP) HPLC and size-exclusion chromatography, as well as circular dichroism. Nanofiber/nanoparticle composite scaffold was demonstrated to have appropriate mechanical properties as a wound dresser and a sustained release of functional G-CSF. The PCL/NP(G-CSF) scaffold showed a suitable proliferation and well-adherent morphology of stem cells. In vivo study and histopathological evaluation outcome revealed that skin regeneration was dramatically accelerated under PCL/NP(G-CSF) as compared with control groups. Superior fibroblast maturation, enhanced collagen deposition and minimum inflammatory cells were also the beneficial properties of PCL/NP(G-CSF) over the commercial dressing. The synergistic effect of extracellular matrix-mimicking nanofibrous membrane and G-CSF could develop a suitable supportive substrate in order to extensive utilization for the healing of skin wounds. © 2017 Wiley Periodicals Inc. J Biomed Mater Res Part A: 105A: 2830-2842, 2017.

Progress in the Development of Chitosan-Based Biomaterials for Tissue Engineering and Regenerative Medicine

“…Loading efficiency of GM-CSF was as high as 97.4 ± 1.68% with sustained release of~100% over 48 h and in vivo experiments have shown that composites loaded with encapsulated GM-CSF in CS NPs induce greater wound closure compared to the composite alone [50]. Polycaprolactone nanofibers loaded with CS NPs containing GM-CSF also showed accelerated wound closure [51]. Modification of CS with peptides also promotes wound closure, for example, CS hydrogels made from Ser-Ile-Lys-Val-Ala-Val-chitosan macromers [52] when applied in vivo induces collagen expression, angiogenesis, expression of TGF-β1, and inhibits the expression of TNF-α, IL-1β, and IL-6 mRNA in a mouse skin wound model [53].…”

Recent Advances in the Controlled Release of Growth Factors and Cytokines for Improving Cutaneous Wound Healing

“…Moreover, to increase cell attachment, the scaffold was coated with collagen I. In vivo experiments demonstrated improved wound closure, scar reduction, fibroblasts maturation, as well as increased collagen density and a decreased amount of neutrophils (Tanha et al, 2017).…”

Functional Nanofibrous Biomaterials of Tailored Structures for Drug Delivery—A Critical Review

“…This morphology of nanofibers can be employed to repair skin tissue in wound healing, as the ECM fibers of skin are also unaligned. For example, isotropic PCL nanofibers have been used to adsorb chitosan nanoparticles containing human granulocyte colony stimulating factor (G-CSF) for skin tissue regeneration [111]. Additionally, heparin mimetic peptide nanofibers with unaligned morphology dramatically promoted the tissue regeneration of burn injury [112].…”