Electrospun Fibers with Plasmid bFGF Polyplex Loadings Promote Skin Wound Healing in Diabetic Rats

Abstract

Deep or chronic skin wounds are difficult to heal spontaneously due to the lack of scaffold to guide cell growth and reduced levels and activities of endogenous growth factors. Emulsion electrospinning process integrated with DNA condensation techniques indicated potentials to gradually release DNA, but no attempt has been made to clarify the advantages in promoting tissue regeneration and wound recovery. In this study, polyplexes of basic fibroblast growth factor-encoding plasmid (pbFGF) with poly(ethylene imine) were incorporated into electrospun fibers with a core-sheath structure, and poly(ethylene glycol) was included into the fiber sheath to allow a sustained release of pbFGF for 4 weeks. In vitro tests on mouse embryo fibroblasts indicated that pbFGF-loaded fibrous mats enhanced cell proliferation by the autocrine bFGF, and an effective cell transfection proceeded for over 28 days. Skin wounds were created in the dorsal area of diabetic rats for in vivo evaluation of skin regeneration after being covered with pbFGF-loaded fibrous mats. The gradual pbFGF release revealed significantly higher wound recovery rate with improved vascularization, enhanced collagen deposition and maturation, complete re-epithelialization and formation of skin appendages. The above results demonstrate the potential use of pbFGF-loaded electrospun fibrous mats to accelerate the healing of skin ulcers for patients with diabetic mellitus.

Substrate topography: A valuable in vitro tool, but a clinical red herring for in vivo tenogenesis

“…Further, in a subcutaneous model, none of the substrates induced cellular orientation parallel to the direction of the substrate topography. It is tempting to hypothesise that two-dimensional imprinted substrates are overwhelmed with body fluids and protein adsorption upon implantation, prohibiting favourable cell / material interaction at the substrate-tissue nano-biointerface and that three-dimensional fibrous constructs are more effective for directional neural [77][78][79], tendon [29,35,80], bone [81][82][83] and skin [84][85][86] neotissue formation and promote relatively enhanced cell growth, motility, matrix deposition and neotissue growth through the provision of a true three-dimensional environment.…”

Biochemical and Biophysical Cues in Matrix Design for Chronic and Diabetic Wound Treatment

“…Kulkarni et al encapsulated lipoplexes carrying eNOS encoding gene in fibrin microspheres and formed a ''fibrin in fibrin'' temporal release system. 135 Electrospun fibers have been immobilized with plasmids to sustainably deliver bFGF 136 and EGF. 137 Small interfering RNA.…”

A novel electrospun membrane based on moxifloxacin hydrochloride/poly(vinyl alcohol)/sodium alginate for antibacterial wound dressings in practical application

“…The calculated average diameter of the healing residue area was used to determine the healing percentage (Yang et al, 2011;Charernsriwilaiwat et al, 2012) following equation:…”

“…Re-epithelialization on the granulation tissue in open wound, forming a barrier between the wound and the environment, is one of the most important indicators for skin healing (Yang et al, 2011). The HE staining of the wound areas in different groups is shown in Figure 8.…”