R. Jayakumar

Biomaterials based on chitin and chitosan in wound dressing applications.

Wound dressing is one of the most promising medical applications for chitin and chitosan. The adhesive nature of chitin and chitosan, together with their antifungal and bactericidal character, and their permeability to oxygen, is a very important property associated with the treatment of wounds and burns. Different derivatives of chitin and chitosan have been prepared for this purpose in the form of hydrogels, fibers, membranes, scaffolds and sponges. The purpose of this review is to take a closer look on the wound dressing applications of biomaterials based on chitin, chitosan and their derivatives in various forms in detail.

Novel chitin and chitosan nanofibers in biomedical applications

Chitin and its deacetylated derivative, chitosan, are non-toxic, antibacterial, biodegradable and biocompatible biopolymers. Due to these properties, they are widely used for biomedical applications such as tissue engineering scaffolds, drug delivery, wound dressings, separation membranes and antibacterial coatings, stent coatings, and sensors. In the recent years, electrospinning has been found to be a novel technique to produce chitin and chitosan nanofibers. These nanofibers find novel applications in biomedical fields due to their high surface area and porosity. This article reviews the recent reports on the preparation, properties and biomedical applications of chitin and chitosan based nanofibers in detail.

Flexible and microporous chitosan hydrogel/nano ZnO composite bandages for wound dressing: in vitro and in vivo evaluation.

Current wound dressings have disadvantages such as less flexibility, poor mechanical strength, lack of porosity, and a tendency for dressings to adhere onto the wound surface; in addition, a majority of the dressings did not possess antibacterial activity. Hydrogel-based wound dressings would be helpful to provide a cooling sensation and a moisture environment, as well as act as a barrier to microbes. To overcome these hassles, we have developed flexible and microporous chitosan hydrogel/nano zinc oxide composite bandages (CZBs) via the incorporation of zinc oxide nanoparticles (nZnO) into chitosan hydrogel. The prepared nanocomposite bandages were characterized using Fourier transform infrared spectroscopy (FT-IR), X-ray diffractometry (XRD), and scanning electron microscopy (SEM). In addition, swelling, degradation, blood clotting, antibacterial, cytocompatibility, cell attachment on the material, and cell infiltration into the composite bandages were evaluated. The nanocomposite bandage showed enhanced swelling, blood clotting, and antibacterial activity. Cytocompatibility of the composite bandage has been analyzed in normal human dermal fibroblast cells. Cell attachment and infiltration studies showed that the cells were found attached to the nanocomposite bandages and penetrated into the interior. Furthermore, the in vivo evaluations in Sprague-Dawley rats revealed that these nanocomposite bandages enhanced the wound healing and helped for faster re-epithelialization and collagen deposition. The obtained data strongly encourage the use of these composite bandages for burn wounds, chronic wounds, and diabetic foot ulcers.

Sodium alginate/poly(vinyl alcohol)/nano ZnO composite nanofibers for antibacterial wound dressings

Sodium alginate (SA)/poly (vinyl alcohol) (PVA) fibrous mats were prepared by electrospinning technique. ZnO nanoparticles of size ∼160nm was synthesized and characterized by UV spectroscopy, dynamic light scattering (DLS), XRD and infrared spectroscopy (IR). SA/PVA electrospinning was further carried out with ZnO with different concentrations (0.5, 1, 2 and 5%) to get SA/PVA/ZnO composite nanofibers. The prepared composite nanofibers were characterized using FT-IR, XRD, TGA and SEM studies. Cytotoxicity studies performed to examine the cytocompatibility of bare and composite SA/PVA fibers indicate that those with 0.5 and 1% ZnO concentrations are less toxic where as those with higher concentrations of ZnO is toxic in nature. Cell adhesion potential of this mats were further proved by studying with L929 cells for different time intervals. Antibacterial activity of SA/PVA/ZnO mats were examined with two different bacteria strains; Staphylococcus aureus and Escherichia coli, and found that SA/PVA/ZnO mats shows antibacterial activity due to the presence of ZnO. Our results suggest that this could be an ideal biomaterial for wound dressing applications once the optimal concentration of ZnO which will give least toxicity while providing maximum antibacterial activity is identified.f.

Curcumin-loaded biocompatible thermoresponsive polymeric nanoparticles for cancer drug delivery

This study aims at the formulation of curcumin with biodegradable thermoresponsive chitosan-g-poly (N-vinylcaprolactam) nanoparticles (TRC-NPs) for cancer drug delivery. The spherical curcumin-loaded nanoparticles of size 220 nm were characterized, and the biological properties were studied using flow cytometry and cytotoxicity by MTT assay. The in vitro drug release was higher at above LCST compared to that at below LCST. TRC-NPs in the concentration range of 100-1000 μg/mL were non-toxic to an array of cell lines. The cellular localization of the curcumin-loaded TRC-NPs was confirmed from green fluorescence inside the cells. The time-dependent curcumin uptake by the cells was quantified by UV spectrophotometer. Curcumin-loaded TRC-NPs showed specific toxicity to cancer cells at above their LCST. Flow cytometric analysis showed increased apoptosis on PC3 compared to L929 by curcumin-loaded TRC-NPs. These results indicate that novel curcumin-loaded TRC-NPs could be a promising candidate for cancer drug delivery.

Wet chemical synthesis of chitosan hydrogel–hydroxyapatite composite membranes for tissue engineering applications

Chitosan, a deacetylated derivative of chitin is a commonly studied biomaterial for tissue-engineering applications due to its biocompatibility, biodegradability, low toxicity, antibacterial activity, wound healing ability and haemostatic properties. However, chitosan has poor mechanical strength due to which its applications in orthopedics are limited. Hydroxyapatite (HAp) is a natural inorganic component of bone and teeth and has mechanical strength and osteoconductive property. In this work, HAp was deposited on the surface of chitosan hydrogel membranes by a wet chemical synthesis method by alternatively soaking the membranes in CaCl(2) (pH 7.4) and Na(2)HPO(4) solutions for different time intervals. These chitosan hydrogel-HAp membranes were characterized using SEM, AFM, EDS, FT-IR and XRD analyses. MTT assay was done to evaluate the biocompatibility of these membranes using MG-63 osteosarcoma cells. The biocompatibility studies suggest that chitosan hydrogel-HAp composite membranes can be useful for tissue-engineering applications.

Chitin Scaffolds in Tissue Engineering

Tissue engineering/regeneration is based on the hypothesis that healthy stem/progenitor cells either recruited or delivered to an injured site, can eventually regenerate lost or damaged tissue. Most of the researchers working in tissue engineering and regenerative technology attempt to create tissue replacements by culturing cells onto synthetic porous three-dimensional polymeric scaffolds, which is currently regarded as an ideal approach to enhance functional tissue regeneration by creating and maintaining channels that facilitate progenitor cell migration, proliferation and differentiation. The requirements that must be satisfied by such scaffolds include providing a space with the proper size, shape and porosity for tissue development and permitting cells from the surrounding tissue to migrate into the matrix. Recently, chitin scaffolds have been widely used in tissue engineering due to their non-toxic, biodegradable and biocompatible nature. The advantage of chitin as a tissue engineering biomaterial lies in that it can be easily processed into gel and scaffold forms for a variety of biomedical applications. Moreover, chitin has been shown to enhance some biological activities such as immunological, antibacterial, drug delivery and have been shown to promote better healing at a faster rate and exhibit greater compatibility with humans. This review provides an overview of the current status of tissue engineering/regenerative medicine research using chitin scaffolds for bone, cartilage and wound healing applications. We also outline the key challenges in this field and the most likely directions for future development and we hope that this review will be helpful to the researchers working in the field of tissue engineering and regenerative medicine.

Preparative methods of phosphorylated chitin and chitosan—An overview

Biomaterials such as chitin, chitosan and their derivatives have a significant and rapid development in recent years. Chitin and chitosan have become cynosure of all party because of an unusual combination of biological activities plus mechanical and physical properties. However, the applications of chitin and chitosan are limited due to its insolubility in most of the solvents. The chemical modification of chitin and chitosan are keen interest because of these modifications would not change the fundamental skeleton of chitin and chitosan but would keep the original physicochemical and biochemical properties. They would also bring new or improved properties. The chemical modification of chitin and chitosan by phosphorylation is expected to be biocompatible and is able to promote tissue regeneration. In view of rapidly growing interest in chitin and chitosan and their chemical modified derivatives, we are here focusing the recent developments on preparation of phosphorylated chitin and chitosan in different methods.

Biocompatible, biodegradable and thermo-sensitive chitosan-g-poly (N-isopropylacrylamide) nanocarrier for curcumin drug delivery

A nano formulation of curcumin loaded biodegradable thermoresponsive chitosan-g-poly (N-isopropylacrylamide) co-polymeric nanoparticles (TRC-NPs) (150 nm) were prepared by ionic cross-linking method and characterized. The in vitro drug release was prominent at above LCST. Cytocompatibility of TRC-NPs (100-1000 μg/ml) on an array of cell line is proved by MTT assay. The drug loaded TRC-NPs showed specific toxicity on cancer cells. The cell uptake studies were confirmed by fluorescent microscopy. Flowcytometric analysis of curcumin loaded TRC-NPs showed increased apoptosis on PC3 cells. These results indicated that TRC-NPs could be a potential nanovehicle for curcumin drug delivery.

Preparation and characterization of novel β-chitin-hydroxyapatite composite membranes for tissue engineering applications

Beta-chitin is a biopolymer principally found in shells of squid pen. It has the properties of biodegradability, biocompatibility, chemical inertness, wound healing, antibacterial and anti-inflammatory activities. Hydroxyapatite (HAp) is a natural inorganic component of bone and teeth and has osteoconductive property. In this work, beta-chitin-HAp composite membranes were prepared by alternate soaking of beta-chitin membranes in CaCl2 (pH 7.4) and Na2HPO4 solutions for 2 h in each solution. After 1, 3 and 5 cycles of immersion, beta-chitin membranes were characterized using the SEM, FT-IR, EDS and XRD analyses. The results showed the presence of apatite layer on surface of beta-chitin membranes, and the amounts of size and deposition of apatite layers were increased with increasing number of immersion cycles. Human mesenchymal stem cells (hMSCs) were used for evaluation of the biocompatibility of pristine as well as composite membranes for tissue engineering applications. The presence of apatite layers on the surface of beta-chitin membranes increased the cell attachment and spreading suggesting that beta-chitin-HAp composite membranes can be used for tissue engineering applications.