Acceleration of skin regeneration in full-thickness burns by incorporation of bFGF-loaded alginate microspheres into a CMCS-PVA hydrogel

Abstract

Two important issues in skin tissue engineering are the vascularization and regeneration of the dermis. Basic fibroblast growth factor (bFGF) is known to promote angiogenesis and accelerate wound healing. Direct delivery of bFGF to the wound area, however, would lead to a loss of bioactivity. To this end, bFGF-loaded alginate microspheres (Ms) were fabricated and incorporated into carboxymethyl chitosan (CMCS)-poly(vinyl alcohol) (PVA) to form a composite hydrogel. Scanning electron microscopy (SEM) results indicated that the incorporation of Ms does not significantly affect the inner structure of CMCS-PVA. In an in vitro study, the release of bFGF from Ms-CMCS-PVA in a sustained manner retained higher bioactivity over a 2-week period. Full-thickness burn wounds were created in the dorsal area of rats for in vivo evaluation of skin regeneration treated with CMCS-PVA hydrogel, with and without bFGF. Compared with the control, CMCS-PVA and bFGF-CMCS-PVA groups, the bFGF/Ms-CMCS-PVA group revealed significantly faster wound recovery rates, with re-epithelialization and regeneration of the dermis. Moreover, the bFGF/Ms-CMCS-PVA group had the highest density of newly formed and mature blood vessels during the 2 mweek treatment period. The ability of the bFGF/Ms-CMCS-PVA hydrogel to accelerate wound healing in a full-thickness burn model suggests its potential for use in dermal tissue regeneration. Copyright © 2015 John Wiley & Sons, Ltd.

Hydrogels based on chitosan in tissue regeneration: How do they work? A mini review

“…Skin is a layered organ that consists of more than 50% water, but is very stiff (having elastic moduli of up to 100 MPa) as well as tough and hard to break (with fracture energies of up to 9000 kg s −2 ) . Full‐thickness skin loss is a typical but intractable clinical issue, which is primarily caused by trauma, burns, and chronic diseases such as diabetes mellitus . Usually, the defected skin fails to renew itself due to a lack of dermis and the attack of infections .…”

“…that the hydrogels made of chitosan, poly(ethylene glycol) and polyvinylpyrrolidone could work as antimicrobial and scar preventive dressings. Moreover, chitosan‐based hydrogels are regarded as carriers to deliver the therapeutic drugs topically, such as vancomycin, peptide Ser‐Ile‐Lys‐Val‐Ala‐Val, melatonin, tigecycline, bFGF, and honey bee . These drugs have at least one of following functions: (1) antibacterial; (2) anti‐inflammatory; (3) angiogenesis; and (4) the promotion of fibroblast proliferation, thus, facilitating to skin repair.…”

Carboxymethyl chitosan nanoparticles loaded with bioactive peptide OH-CATH30 benefit nonscar wound healing

“…[36][37][38] Cytokine FGFs were incorporated into composite CMCS hydrogel for accelerating skin regeneration by enhancing skin permeability and avoiding rapid degradation. 18 CMCS-encapsulated insulin showed better outcomes in epithelial permeation, bioavailability, and half-time than single insulin application. 21 Human LL-37 is a well-documented molecule that belongs to the cathelicidin family and has important roles in innate immunity.…”

“…Due to their favorable biocompatibility, no antigenicity, moisture retention, specific bioadhesion, and antibacterial ability, CS and CMCS are regarded as attractive materials for wound healing agents. 18,19 Recently, they have also been applied as the polymer materials for the bioactive peptide delivery. Insulin was successfully encapsulated in CMCS nanocarriers under mild conditions and showed improvement in animal models.…”

Current status and future outlook of nano‐based systems for burn wound management

“…Mice Third 92-95 10 10 × 10 mm 2 (Dai, Tegos et al, 2009) Rat Second or third 180 15 2 × 2 cm 2 (Shettigar, Jagannathan et al, 1982) Rat Second NR 10 1 × 1 cm 2 (de Almeida, Cardoso et al, 2013) Pig NR 90 20 5 × 5 cm 2 (Nunes, Rabelo et al, 2016) Mice Partial-thickness 70 (hot water) 4 15 × 15 mm 2 (Ito, Saito et al, 2015) Pig Third 100 30 5 × 5 cm 2 (Boucard, Viton et al, 2007) Rat Second 94 (hot water) 15 r = 1 cm (Alemdaroglu, Degim et al, 2006) NR Third 200 30 NR (Shen, Song et al, 2015) Pig Partial-thickness 100 22 d = 3 cm (Cylandeical) (Roy, Tomblyn et al, 2016) Rat Full-thickness 90 20 ф = 15 mm (circular) (Liu, Huang et al, 2017) Rat Full-thickness 85 20 d = 1.5 cm (rod) (Gupta, Upadhyay et al, 2013) Rat Full-thickness 85 15 NR (Heo, Yang et al, 2013) Rat Second 90 8 d = 3 cm (circular) (Meng, Chen et al, 2009) Rat Second 99 (water steam) 13 20 × 20 mm 2 (square) (Liu, Lin et al, 2012) Rat Second 90 10 2 × 3 cm 2 (Kossovich, Salkovskiy et al, 2010) Rat NR NR 10 250 mm 2 (MH, Saraswathi et al, 2010) NR Partial-thickness burn wound 80 10-12 min 300 mm 2 (Kumar, Khan et al, 2013) NR Full-thickness 100 8 NR (Abdullahi, Amini-Nik et al, 2014) Abbreviations: NR, not reported; R, radius; d, diameter; ф = area.…”