Evaluation of a Wound Dressing Composed of Hyaluronic Acid and Collagen Sponge Containing Epidermal Growth Factor in Diabetic Mice

Abstract

This study investigated the effect of a wound dressing composed of hyaluronic acid (HA) and collagen (Col) sponge containing epidermal growth factor (EGF) on wound healing in diabetic mice. High-molecular-weight (HMW) HA aqueous solution, hydrolyzed low-molecular-weight (LMW) HA aqueous solution and heat-denatured Col aqueous solution were mixed, followed by freeze-drying to obtain a spongy sheet. Cross-linkage between Col molecules was induced by UV irradiation to the spongy sheet (Type-I wound dressing). In a similar manner, a spongy sheet containing EGF (Type-II wound dressing) was prepared by freeze-drying the mixed solution of HMW-HA, LMW-HA and Col containing EGF. The efficacy of these products was evaluated in type-II diabetic BKS.Cg-+Lepr(db)/+Lepr(db) (db/db) mice. Wound dressings were applied to a full-thickness, dorsal skin defect measuring 1.5 cm × 2.0 cm, showing adipose tissue. In the control group, a commercially available artificial dermis composed of collagen spongy sheet (TERUDERMIS(®)) was used. A commercially available polyurethane film dressing (Bioclusive(®)) was applied over each wound dressing. After 1 week of application, wound conditions were evaluated based on their gross and histological appearances. Type-I and -II wound dressings promoted a decrease in wound size associated with angiogenesis and granulation tissue formation, compared with the artificial dermis. In particular, Type-II wound dressings promoted sufficient re-epithelialization. These findings indicate that the combination of HA, Col and EGF promotes wound healing by stimulating cell activity including cell migration and proliferation on the adipose tissue in a diabetic wound. Type-I and -II wound dressings would be useful to prepare a well-vascularized wound bed acceptable for split-thickness auto-skin grafting.

Recent advances on the development of wound dressings for diabetic foot ulcer treatment—A review

“…In general terms, collagens are rod-type proteins with typical molecular weights around 300 000 g mol À1 that also present high mechanical strength and good biocompatibility (although they may present some antigenicity) [101,164]. Collagen can form stable fibers and its mechanical, degradation and water-uptake properties can be further enhanced by chemical cross-linking (using glutaraldehyde [165], genipin [166], carboiimide [167], hexamethylene diisocyanate [168]), by physical cross-linking (using freeze-drying) [169] or by binding with other protein/polymers [170,171]. Low inflammatory and cytotoxic responses and biodegradability are other attractive properties of collagen [102].…”

A review of bioactive plant polysaccharides: Biological activities, functionalization, and biomedical applications

“…The incorporation of nanosilver particles provided a strong antimicrobial effect and therefore made such polyvinyl pyrrolidone/alginate hydrogels suitable for use as wound dressing. Except the alginate and its various derivatives, other natural polysaccharides such as cellulose, chitin, chitosan, and hyaluronic acid have also been explored for wound dressing or wound healing applications (Anisha, Biswas, Chennazhi, & Jayakumar, 2013;Kondo, Niiyama, Yu, & Kuroyanagi, 2011;Matsumoto & Kuroyanagi, 2010). …”

Innovations in gene and growth factor delivery systems for diabetic wound healing

“…Collagen‐based scaffolds alone (Moura et al, ) and in combination with other natural polymers such as gelatine (Kanda et al, ), hyaluronic acid (Kondo, Niiyama, Yu, & Kuroyanagi, ) and chitosan (Wang et al, ), or synthetics such as PGA (Nagato, Umebayashi, Wako, Tabata, & Manabe, ) have been examined for their candidacy as GFs‐releasing wound dressings. The freeze‐drying technique has been conventionally used to develop such scaffolds (Kondo et al, ; Moura et al, ; Nagato et al, ), which are subjected to crosslinking via chemical (Moura et al, ), ultraviolet (UV)‐irradiation (Kondo et al, ) or thermal treatment (Nagato et al, ) to induce structural stability. From a therapeutic perspective, combining collagen with other polymers to generate a composite scaffold is particularly attractive because it can offer improved resistance to collagenase digestion and also sustain the release of GFs with a slower rate (Wang et al, ).…”