ReviewRecent advances on biomedical applications of pectin-containing biomaterials
Graphical abstract
Introduction
Nowadays, biomaterials with unique properties generating considerable interest in biomedical applications, such as tissue engineering, wound healing, drug delivery, and the developing of biosensors. Synthetic and natural polymers are well-known candidates for the fabrication of these biomaterials [1], [2], [3], [4]. Various biomaterial formulations have been developed for biomedical applications such as hydrogels, films, nanoparticles, and nanocomposites [5], [6], [7], [8]. Among the above-mentioned formulations, hydrogels have gained increasingly attraction owing to their interesting features including, biocompatibility, biodegradability, unique “soft-wet” nature, and similarity to biological tissue [9], [10], [11], [12], [13], [14], [15]. Hydrogels are 3D crosslinked polymeric materials with high water content and the ability to absorb and hold a large amount of body fluid. The soft nature of hydrogels and the ability to the maintenance of a moist environment minimizes irritation to the surrounding tissues and encourages tissue formation which makes them a potential candidate for tissue engineering applications [11], [16], [17], [18]. Moreover, their magnificent tissue compatibility, easy utilization, and solute permeability have played a substantial role in the development of drug delivery [19], [20]. Despite these outstanding advantages, the hydrogels bioapplications encounter some challenges because of a few limitations including mechanical weakness, water sensitivity, instability under physiological conditions, and unpredictable behavior in long-term applications [21]. There are two types of polymeric materials; synthetic and natural (biopolymer). Natural polymers have distinct advantages over synthetic analogous due to their biodegradability and biocompatibility in alive systems. The major drawbacks to exploiting natural polymers are their weak mechanical strength in comparison with synthetic ones which makes them vulnerable for various biomedical applications. On the other hand, many published reports have revealed that most synthetic polymers have several shortcomings, such as high cytotoxicity and low biocompatibility [22], [23]. Biopolymers are constructed by the living cells and consist of monomeric units that are covalently bonded to form larger biomolecules. They are categorized into three subsets: polynucleotides, polypeptides, and polysaccharides. Polysaccharides are linear or branched polymeric carbohydrates composed of monosaccharide units bound together by glycosidic linkages and examples include cellulose, chitosan (CS), alginate (Alg), and pectin (Pec). Pec is a water-soluble anionic heteropolysaccharide obtained from the primary cell walls of terrestrial plants such as sunflower heads and citrus fruits using chemical or enzymatic methods [24]. Chemically; Pec is composed of partially esterified/amidated galacturonic acid (GalA) residues linked by linear 1,4-glycosidic linkage with varying degrees of methylation of carboxylic acid residues [25]. A low degree of methylation led to the gel formation in presence of multivalent ions whereas a higher degree of methylation forms gels in acidic media with the addition of different sugars [26], [27]. In addition, the degree of esterification of galacturonic acid residues of Pec changes the solubility of Pec and influences its gelling and film-forming properties [28].
Pec heteropolysaccharides are promising candidates for various biomedical applications including skin and bone tissue engineering [29], [30], wound dressings [31], and drug delivery systems [32], [33], [34] due to their non-toxicity, low-cost, anti-bacterial, and anti-inflammatory properties. Considering the good biocompatibility [35], biodegradability [36], [37], and published reports that showed Pec capability in inhibiting the activity of macrophages and neutrophils and having an anti-inflammatory effect [38], [39], [40], it could be concluded that Pec has great potential for tissue engineering applications. In the field of bone tissue engineering, Pec materials are able to induce the nucleation of minerals if they are immersed in proper physiological conditions led to forming biomimetic constructs that better mimic the natural architecture of the bone [41]. Pec gelation is promoted by cross-linking with calcium ions. Intermolecular cross-links were formed between the divalent calcium ions and the negatively charged carboxyl groups of the Pec molecules resulted in an egg-box bundle with a cavity in which the calcium ions may pack or be coordinated [42], [43]. This interesting gelling properties besides the strong anti-inflammatory effect is very desirable for wound healing application such as burns and chronic diabetic wounds [44]. In addition, the acceptable stability of Pec under acidic conditions and higher temperature provides delivery systems for loading and releasing drugs at the target site. For instance, recently Pec-based materials were used for colon targeting drug delivery since it is almost totally degraded by colonic bacteria but it is resistant to proteases and amylase which is active in the upper gastrointestinal tract (GIT) [45], [46].
Section snippets
Wound healing
Nowadays, designing and developing an effective wound dressing, especially for crucial injuries, is a major challenge in the world. Due to the time-consuming process of wound regeneration, many efforts have been done to produce an efficient bandage with the suitable potential to close the wounds and accelerate the sore healing procedure [47]. An ideal wound dressing should be able to create a moist environment for wound healing because, during the restoration process, wet conditions compared to
Outlook and perspective
Pec is a natural polysaccharide made by methylated ester of polygalacturonic acid and is divided into two major groups regarding their degree of esterification (low-methoxyl and high-methoxyl Pec). The most important factors that make Pec an ideal candidate for bioapplications are its biodegradability and gel-forming capability. Gel formation is directed by hydrogen bond formation between free carboxyl groups on the Pec molecules and also between the hydroxyl groups of neighboring molecules.
Conclusions
In this study, recent appealing applications of a natural heteropolysaccharide, Pec, are reviewed. Pec has been extensively used in the food industry as a stabilizer agent and its application in biological fields attracted scientist's attention owing to its unique properties including easy gelling, biocompatibility, biodegradability, and low cost. Pec can be easily employed in the form of hydrogels, films, scaffolds, and nanoparticles. Among them, Pec -based hydrogels are growingly studied and
Declaration of competing interest
The authors whose names are listed in this article have no competing interests or other conflict of interests that might be perceived to influence the results and/or discussion reported in this paper.
Acknowledgements
The authors gratefully acknowledge the partial support from the Research Council of the Iran University of Science and Technology.
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