Characterization of hydroxyapatite-containing alginate–gelatin composite films as a potential wound dressing

Abstract

In this study, hydroxyapatite (HA)-containing alginate–gelatin films were prepared by solution casting method by blending alginate (A) and gelatin (G) solutions, followed by crosslinking with calcium chloride. HA (1, 2, 5, 10, 20% w/w) was added to film solutions prepared at different ratios (A:G = 40:60, 50:50, and 60:40) and the swelling and degradation behavior, mechanical, antimicrobial and thermal properties, and morphologies of the obtained films were examined. The release of tetracycline hydrochloride (TH), selected as a model drug, from the prepared films was studied. It was observed that the swelling ratio and weight loss of the films decreased as the amounts of alginate and HA increased. Scanning electron microscopy analysis indicated that as the amount of HA in the films increased, the film surface becomes rougher. The mechanical properties of the films were affected by the amount of HA and the A:G ratio. Incorporation of HA increased the thermal stability of films. The amount of TH released from the films within 15 min decreased as the amounts of alginate and hydroxyapatite increased. It was found that films containing TH showed slightly higher antimicrobial activity against Staphylococcus aureus than Escherichia coli.

Introduction

Recently, various biopolymers have been investigated for the development of wound dressing materials [1]. Among these polymers, alginate and gelatin have received increased attention because they are cheap, biodegradable, biocompatible and well tolerated by the immune system [2]. Alginate, obtained from brown algae, possesses a linear structure and is composed of two 1–4 linked β‑d‑mannuronate and α‑l‑guluronate residues [3]. It has been shown that alginate can create crosslinked gels with divalent cations or other polymers, such as gelatin, to produce potential wound dressing materials [[3], [4], [5]]. Gelatin is another natural biopolymer and it is obtained by controlled hydrolysis of fibrous insoluble collagen, which is the main component of skin and tissue [6]. Gelatin has been used for various applications, such as wound dressings, adhesive, and adsorbent pads owing to its wound healing properties and superior biocompatibility [4,6,7].

Despite their film-forming ability, gelatin and alginate films are rarely used alone owing to their poor mechanical strength and low thermal stability [8,9]. One possible approach to improve the performance of polymeric materials is through blending of biopolymers [6,10,11]. Studies have shown that composite films obtained by blending of alginate and gelatin show better mechanical and physical properties compared to those of single polymer films [[12], [13], [14]]. However, it should be highlighted that blending of these polymers results in only weak secondary forces leading to insufficient mechanical properties after the absorption of wound exudates [4]. A recent method was proposed to cope with this problem involving incorporation of a biocompatible filler into the wound dressing material. Particular focus can be given to hydroxyapatite as a filler material, which is a suitable biomineral for addition to wound dressing materials owing to its biocompatibility, non-toxicity, and non-immunogenicity [14,15]. It has been reported that the addition of hydroxyapatite into biomaterials results in improved mechanical, barrier, and thermal properties [[16], [17], [18], [19], [20]]. Although several polymers have been used to prepare composite wound dressing with several types of fillers [6,21,22], to date hydroxyapatite-containing alginate–gelatin composite biomaterials have not been considered as wound dressing. To the best of my knowledge, this is the first study that demonstrates the preparation of alginate-gelatin-hydroxyapatite composite films obtained by solvent casting method. There are many methods that can be used to produce hydroxyapatite containing composite materials, such as thermo-mechanical mixing, in situ precipitation, in situ polymerization and sol-gel method [23]. In this study, solution casting was used to produce HA containing wound dressing since it is simple, easy, and inexpensive and there is no need for specialized equipment and toxic solvents [24].

The novelty of this work is that alginate-gelatin and hydroxyapatite have been combined for the first time to prepare wound dressing material and simple method of synthesis. It seems that more exact and comprehensive investigations are required to examine the application of hydroxyapatite-alginate-gelatin composite materials as a wound dressing obtained by solvent casting. Thus, the main objective of this study was to characterize the in vitro properties of hydroxyapatite containing alginate/gelatin composite films, but medical application of obtained materials fall outside the scope of this article.

In this study, sodium alginate–gelatin composite films were prepared by varying the weight ratio of sodium alginate and gelatin (40:60, 50:50, and 60:40) and incorporating varying concentrations of hydroxyapatite (1, 2, 5, 10, and 20% w/w) into the film solution to examine whether hydroxyapatite addition modifies the physical, mechanical, thermal and antimicrobial properties of the films. Tetracycline hydrochloride was chosen as a model drug and its release from the films was investigated in water.