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Abstract

Recently the replacing of the petrochemical origin polymers with biopolymers and biocomposites which are environmental biodegradable polymers became a growing interest. The use of gamma radiation for synthesis and produce further modification of the biopolymers and biocomposites found to be suitable for biomedical application due to none using of toxic additives. Moreover, the radiation technique is the combining of preparation and sterilization in a one technological step thus, reducing time of the production and lower the costs. The use of gamma radiation technique in biomedical application is growing rapidly in controlled drug delivery, injectable materials, wound dressing, tissue engineering, immobilized enzymes and biosensors.

Keywords

Radiation technique natural polymers biopolymers biocomposites biomedical applications

Introduction

The application of biopolymers and biocomposites in biomedical and biotechnological¹ including, injectable formulations, topical dressings, implants, diagnostic assays, controlled drug release devices, purification processes, separation techniques, cell bioprocesses, immobilization of enzymes and surfaces of cell culture.

The biopolymers and biocomposites are naturally derived polymers or they are combined with synthetic polymers such as LDPE, PP and PS^2–4 that could be used for any time, as a part of the system or as a whole which augments, treats, or replaces any organ, tissue or function of the body without led to local toxicity or non-desired reactions. Thus they could either be used for long or short term or implanted in externally applications.

Radiation processing is commonly used^5–9 to produce biological and chemical changes in the irradiated biopolymers and biocomposites. The using of other curing or treated sources such as UV, laser, glow discharge, visible light, and incoherent dielectric excimer lamps are closely similar to irradiation processing but with lower changes. Therefore, there is interest to use radiation techniques to prepare and modify different types and forms of the naturally derived biopolymers and biocomposites, and to add different function groups to the surfaces of these new polymers to be applied in biomedicine and biotechnology fields.

The novelty of the use of gamma irradiation as a successful technique to induce further modification of the prepared biopolymers and biocomposites without adding of any toxic additives as used in other ordinary chemical techniques.^6–9

The use of high-energy ionizing radiations especially gamma rays is rapidly growing in many sectors.⁵ The prepared biopolymers and biocomposites which modified by gamma radiation technique will have a long shelf life and be sterilized in one step. Moreover, the water resistance and mechanical properties of the radiation cured biopolymers will be further modified through crosslinking by gamma radiation. Also, the gamma radiation technique is suitable than other classical chemical initiation methods due to a number of advantages^5–9:-

• The absence of toxic additives such as initiators, catalysts which could contaminate the final product.

• Initiation of many reactions between monomers and polymers which cannot be react or polymerized by ordinary chemical methods.

• Controlling the grafting processes using different monomers and crosslinking procedure.

• Can control the depth of the surface modification without affecting the bulk properties

• Preparation and sterilization in one step

• Immobilization of bioactive materials without any loss in their activity.

Therefore, it is expected that the non-expensive radiation modified biopolymers and biocomposites could be alternatives to the synthetic origin polymers, where it can be applied in biomedicine and biotechnology fields.

Sources and types of biopolymers

Different natural sources of biopolymers are including polypeptides; polysaccharides; polypeptide/polysaccharide blend, and polynucleotide.

Polypeptides are composed of amino acids and they are containing monomers which are derived from polypeptides alone, as multi-polypeptide complexes or complexes with other proteins molecules, and all have a certain biological function.

Polysaccharides are type of carbohydrates, such as cellulose, starch, chitin, chitosan, pectin, collagen and gelatin. They are consisting of large and long-chain of mono-saccharides joined by glycosidic bonds. They can be classified in various ways and their chains may be branched or un-branched and the mono-saccharides may be of one, two, or more kinds.

Types of polysaccharides

Cellulose is the most abundant and renewable resource on earth that present in 33% of all plant matter. The cellulose content of wood is 50% and that of cotton is 90%.¹⁰ Cellulose will become the main chemical resource in the future.^11,12

Moreover, many new derivatives of cellulose were developed to have wide range of applications, due to the increasing demand for environmentally friendly and biocompatible materials.¹⁰ Cellulose has many reactive hydroxyl groups that can be easily used to prepare hydrogels with good properties,¹³ but there are still needs to study hydrogels based on cellulose for using in biomedical and industrial applications.

Starch is stored in plants in the form of glucose and it is composed of amylopectin (80–90%) and amylose (10–20%).

Dextran is a branched polysaccharide derived from the condensation of glucose. Its main chain consists of α-1,6 glycosidic linkages between glucose monomers, with branches from α-1,3 linkages. This characteristic branching distinguishes a dextran from a dextrin, which is a straight chain glucose polymer tethered by α-1,4 or α-1,6 linkages.¹⁴

Chitin and chitosan are abundant inexpensive polysaccharides containing many reactive amino groups. Chitin is a byproduct of the fishing and the fermentation industries. Chitosan is obtained by deacetylation of chitin.¹⁵

Pectin is a unique carbohydrate fiber rich in galacturonic acid and present in all plants but especially found in fruits and vegetables such as apples or citrus peels which are rich sources of this fiber.

Glycogen is a multi-branched polysaccharide of glucose that act as a form of energy storage in animals, bacteria, and fungi.^16,17

Gelatin is a colorless, translucent, flavorless food ingredient, commonly derived from collagen derived from animal body parts. It is rubbery when moist and brittle when dry. It is referred also as hydrolyzed collagen

Polypeptide and polysaccharide blends are examples of biopolymers that containing polypeptide and polysaccharide in the same chains or as a side chain or vice versa to form large covalently bonded structure. Polysaccharides which are often linearly bonded polymeric carbohydrate structures, and Polypeptides contain short polymeric chains of amino acids.^18–21

The polynucleotides are polymers derived from ribonucleic acid (RNA) and deoxyribonucleic acid (DNA).

Polyhydroxybutyrates are polyesters which produced by certain bacteria combined with cis-1,4-polyisoprene, which is the major component of rubber tree latex.

Sources and types of biocomposites materials

Biocomposites are a combination of synthetic origin polymers and natural polymers as shown in Figure 1. Biocomposites has the same morphology of the living materials with excellent biocompatibility. They protect the natural polymers from mechanical damage and environmental degradation. They are produced from regenerated cellulose, crops, and wood.²²

Figure 1.

The classification of biocomposite materials.

The uses of inorganic or organic fillers have become important in preparing polymeric composites. Polymer composites are commercially prepared for various applications such as biomedical, aerospace components, automobiles, sporting goods,… etc. In the recently 30 years, there is a strong emphasis in the development of polymeric nanocomposites, where the dimensions of the added filler materials are in nanometer. The nanomaterials fillers include nanoparticles such as nano metal oxides nano-clay particles, nano-wires materials, fullerenes, nanofibers, and nano-tubes.^23,24

Environmental impacts of biopolymers and biocomposites

Biopolymers and biocomposites are renewable and sustainable materials due to the fact that they are obtained from plant materials that come from agricultural nonfood crops which can be grown year on year indefinitely. While, the polymers derived from petrochemical origin will eventually run out and they not biodegradable which is harmful to the environment year after year? In addition, biopolymers and biocomposites have the potential to reduce CO₂ quantities in the atmosphere. This is because that they released water H₂O and carbon dioxide CO₂ when they degraded by microorganisms, that can be reabsorbed when plants crops grown.

Natural based biopolymers and biocomposites hydrogels

Biopolymers and biocomposites still new, they are rapidly developing materials, and applied in many fields, such as agriculture, pharmacy, and medicine. Many studies have been reported and published since the 1970s in the new physical and chemical structures, properties and innovative restricted applications of natural based biopolymers and biocomposites hydrogels.²⁵ Also, they found to be compatible with living tissues. In addition the presence of a three-dimensional network in theses hydrogels cause the stability and insolubility of the hydrogel shape because of the fact that it is acts as a cage for the water molecules and other dissolved molecules and ions.

Hydrogels may be based on natural polymers, including macromolecules extracted from seaweed, animal collagen, and plants.²⁶ These natural hydrogels are typically proteins, and polysaccharides which consisted of amino acid and glycosidic repeating units, respectively.

Since many monomers used are toxic or even harmful, particular care is given using radiation technique when using this method for the preparation of hydrogels for biomedical use to ensure that the unreacted residues have been fully extracted in separate reactions.²⁷ There is remarkable and great research interest in hydrogels because they already involved in industrial application and they are promising materials in applications such as in prosthetic materials, soft lenses, biomedical materials for controlled drug release,²⁸ food processing and heavy metals binding. The swollen state results from a balance between dispersing forces acts on hydrated chains and cohesive forces that do not hinder the penetration of the water inside the network.

Applications of natural based biopolymers and biocomposites hydrogels in biomedical application

Wound dressing

The natural based biopolymers and biocomposites for wound healing are used to prevent contamination of a wound by microorganisms from outside, deliver oxygen to the wound, inhibit the loss of body fluids, and generally accelerate healing process.

The application of wound dressing material is to protect the wound from environmental irritants, water and electrolyte disturbances and also inhibits bleeding. The important role of skin is to prevent invasion of microorganisms and homeostasis. Skin must be covered with a dressing immediately after being damaged. There are three categories of wound dressing materials which are synthetic, biologic and synthetic-biologic. Biologic dressings are commonly used such as pigskin and Alloskin but some of their disadvantages namely, that they are poor adhesiveness, risk of cross contamination, limited supplies and high antigenicity. Synthetic dressings induce minimal inflammatory reaction and carry almost no risk of pathogen transmission and have a long shelf life. Synthetic- Biologic dressings are composed of bi-layered, high polymer combined with biologic materials.^29–32 These are the three categories of wound dressing are all commonly used in the clinical setting and they all have disadvantages. An ideal dressing should maintain a moist environment at the wound interface, remove excess exudates allow gaseous exchange and, act as a barrier to microorganisms. It also should be non-allergenic, nontoxic, easily removed without trauma, non-adherent and it should be made from a readily available biomaterial that requires minimal processing, promotes wound healing, and possesses antimicrobial properties.

In the 1980s, hydrogel membranes made from collagen and glycosaminoglycan dermal skin were studied as substrates for cultured human epidermal keratinocytes. A non-porous surface of collagen/glycosaminoglycan was laminated to the membranes to provide a planar substrate for cultured epidermal keratinocytes.³³ These optimized membranes were found to be suitable wound dressing for the culture of human epidermal keratinocytes, and together with the cells yielded a composite material that was histologically similar to skin.^{30,31,34–40}

In the recent years, a large number of research groups were producing improved and a new wound dressing by preparing and modifying biocompatible materials.⁴¹ In order to accelerate the wound repair effect many researchers used biomaterials such as chitin and chitosan which are capable to accelerating the healing processes. Chitin is inexpensive material obtained from the cell wall of fungi or invertebrate’s skeleton. Chitin and chitosan are nontoxic, biodegradable, biocompatible, hydrating agents, and antimicrobial. Because of these properties, they show good positive effects and biocompatibility in wound healing.

Chitin based wound dressings can accelerate regulate secretion of the inflammatory mediators such as interleukin 8, and interleukin 1 β, prostaglandin E and others. This is in addition of repairing of different tissues and facilitating contraction of wounds.^{42, 43}

Chitosan helps in blocks nerve endings reducing pain and natural blood clotting. Chitosan will gradually degrade to release N-acetyl-β-D-glucosamine, which initiates fibroblast proliferation, and stimulates increased level of natural hyaluronic acid synthesis at the wound site and helps in ordered collagen deposition. Furthermore, it helps in scar prevention and faster wound healing.⁴⁴

The prepared biopolymers and biocomposites hydrogel wound dressing should have the following properties:

• Biopolymers and biocomposites hydrogels should have efficient barrier towards bacteria, and also for excessive loss of body fluids,

• Allowing oxygen diffusion towards the wound.

• Being soft and elastic but have strong enough mechanical properties.

• Having good adhesion to the wound therefore, exchange of the dressing without disturbing the healing process or it enables a painless removal,

• Being transparent, so that the healing process can be monitored without the necessity of removing the dressing,

• Enabling an easy treatment of the wound with drugs where of the drug solution can be diffused from the outer surface, or the drug can be injected between the dressing and the wound or by soaking the dressing hydrogel in the drug solution before placing it at the wound.

• Being able to absorb bacterial toxins and exudes.

• It is does not provoke and not make allergic reactions.

• Should lower pain and provides optimal wound healing environment of constant humidity.

• Being sterile, not expensive and easy to use.

• Being able to evaporates water that decreases the temperature of the wound because the most difficult problem in taking care of a burned victim that may have lost most of their body liquid due to exudation and evaporation.

These previous properties accelerate the rate of metabolism and decrease of the body temperature. Thus, the wound dressing hydrogel must avoid or at least reduce the body liquid loss by controlling transmission and absorption as well as by keeping the high humidity in the wound area. On the other hand, if the water vapor transmission rate value (WVTR) is so low, then it will make the accumulation of exudates which may cause the deceleration of healing process and opens up the risk of bacterial growth.

The use of radiation technique for preparing hydrogel wound dressings have many advantages when compared to conventional methods, these include

• Simple, clean and easy technique where there are no byproducts or waste.

• The produced hydrogel wound dressing is safe for the environment and human.

• It does not require special sterile production rooms and a fully sterile product obtained.

• Flexible and easily designed for various method and scale.

• It has been investigated and applied in many countries, e.g. Egypt, China, Japan, Italy, Belarus, Indonesia, Brazil, Malaysia, and Iran.

• Hydrogel covers can also be utilized as emulsions, sprays, creams, and ointments with or without the addition of active compounds.

• All above types of wound dressings and covers can also act as slow-release drug delivery systems, or drugs can be administrated through the hydrogels in situ.⁴⁵

Another classification of wound dressing’s materials is dry and wet wound dressings. It was reported that healing with a wet environment is faster than that with a dry environment.⁴⁶ This is due to the fact that renewed skin, without the formation of eschar, is generating during healing in a wet environment.

Chitin and chitosan based hydrogel membranes have been developed with different types of polymers such as alginate, polyvinyl alcohol, γ-polyglutamic acid, polyethylene glycol diacrylate, hyaluronic acid, and 2-hydroxyethyl methacrylate to improve the wound healing properties.⁴⁷ The composite nature of these hydrogel membranes have the desired properties for wound healing applications. It is confirmed that from previous researches that the Ag/ZnO-incorporated onto chitosan hydrogel membranes are less cytotoxic than other traditionally used dressing materials, and will be very potential wound dressings having antibacterial properties to prevent infections to the an injured skin. Based on the improved antibacterial activity, oxygen permeability, and cell attachment ability, it is concluded that chitosan and chitin scaffolds/sponges could be promising candidate for wound dressing. In the near future chitin and its derivatives will be valid basis in the functionality, versatility and efficacy.

Drug delivery systems

Conventional drug administrations are by oral or by injection are usually results in poor control of the plasma drug concentration while the controlled release of drugs from polymeric hydrogel matrixes has been very successful. Many polymeric devices that deliver drugs at a constant release rate are now commercially available. Controlled drug delivery applications include target delivery systems (insertion at the diseased site) and time.

Mechanism of controlled drug delivery

The classification of controlled drug release systems is based on the mode of the release of the incorporated drug. The three primary mechanisms by which the therapeutic drugs can be released from a delivery system are swelling, diffusion followed by diffusion and polymeric degradation.⁴⁸

Diffusion controlled release

The most common mechanism of controlled drug release depends on diffusion. In diffusion systems the therapeutic drug, which may be either suspended within the polymer matrix or encapsulated in the biopolymers and biocomposites membrane that forms the controlled release device when placed in an aqueous media. The medium diffuses into the matrix, dissolves the incorporated drug, which then diffuses out of its carrier. The diffusion can occur on a macroscopic level and it also takes place at a microscopic scale through pores in the polymer matrix. In the matrix system the drug release rate is time dependent that depends upon the amount of drug present at a particular time.

Swelling-diffusion controlled release

In swelling-diffusion controlled release polymers, the biopolymers and biocomposites hydrogel has to swell to some extent before the drug can diffuse out.

Parameters such as the hydrogel composition, degree of crosslinking density, size, and nature of the incorporated drug molecules play an important role in determining the drug release behavior and thus must be considered during the design of swelling controlled release.⁴⁹ However, presence of hydrophilic groups in the hydrogel network enhances the swelling behavior of the hydrogel. The hydrophobic groups on the other hand reduce the swelling behavior, reduce in the diffusion coefficient values with increased cross-linking density and the increase in the molecular size of the drug reduces the drug release rate.

Drug release through biodegradation

Another interesting property is hydrogel degradation in which the drug is released from the drug carrier device. Biodegradable hydrogels are designed to degrade into smaller molecules which are biologically acceptable to deliver drug into the host.

When the biodegradation occurs through bulk hydrolysis, the biopolymers and biocomposites hydrogel randomly degrades throughout the matrix of the biopolymers and biocomposites. The rate of erosion found to be dependent on the volume of the matrix rather than the thickness, thus in this case the rate of drug release is unpredictable and the dumping effect of the drug dose is commonly observed. This could be solved by the use of highly hydrophobic hydrogels which are contain water labile linkages. These systems undergo surface erosion with minimum internal degradation, thus the release rate is proportional to the biopolymers and biocomposites degradation rate with proper surface geometry.

Many types of drug delivery systems which prepared and composed of crosslinked homo and copolymeric biopolymers and biocomposites.⁵⁰ In most drug delivery biopolymers and biocomposites hydrogels, the rate of diffusion through the bulk depends on two primary factors, water content and the extend of crosslinking. The extent of crosslinking should determine the distance between chains within the biopolymers and biocomposites network, and the extent of swelling. When the entrapped drugs are diffused within the network, the rate of diffusion depends on inter-chain of hydrogel and the size of drug. The most common approach is to design hydrogels with very specific levels of hydrophobicity, and hydrophilicity.

Immobilization of enzymes

Enzymes are efficient catalysts that accelerate wide variety of chemical reactions, and enhance the biochemical reactions of the living cells. They speed up the biochemical reactions by lowering the activation energy without appearing in the reaction products.⁵¹ One of important application of enzymes is that in industrial bioprocesses due to their non-toxicity, good rate of reaction, water solubility which are major advantages over inorganic catalysts,⁵² and also due to their high level of catalytic efficiency, which is more than chemical catalysts.

Enzyme immobilization methods

The different immobilization methods of enzymes are classified as following:-

Physical method; where a weak interaction between enzyme and support material exist. It includes:

• Adsorption on the water insoluble polymer matrix

• Gel entrapment

• Micro encapsulation inside solid membrane hydrogel

Chemical method; where covalent bonds are formed between enzyme and support material it includes:

• Ionic binding

• Covalent bond attachment to a water insoluble solid support (carrier binding method)

• Cross-linking is the use of a multifunctional and low molecular weight reagent.

Urease is a nickel dependent metallo-enzyme, which catalyzes the hydrolysis of urea to carbon dioxide, and ammonia. It is applied in wide applications, such as blood detoxification in removal of urea from beverages, artificial kidneys, and in food industry, and also, in the reduction of urea content in the effluent treatment in agriculture field.

The immobilization conditions of urease on dialdehyde porous starch (DPS) depend on the processing time of immobilization, pH, aldehyde groups’ contents temperature, and ratio of supporter to urease.⁵³ When the immobilized urease stored for 42 days at room temperature, the immobilized urease maintained its original activity while the free urease lost almost all of its activity. It is found that the immobilized urease can be reused for 10 cycles and maintained 75% of its initial activity. The results show that the dialdehyde porous starch (DPS) can be applied as a basis for bioreactor development or biosensor with improved shelf life and reduced costs.

Tissue engineering

The uses of biomedical biopolymers and biocomposites hydrogels over the last years have been extremely successful in most respects.^55–57 The natural biopolymers and biocomposites hydrogels were highly successful to replace natural lens of eye, heart valves, and hips. The major drawback in biomedical applications is that these hydrogels can only perform for short periods of time. The clinical needs are even greater in the case of organs, where replacement by organ transplantation is the only option. The area of tissue engineering offers some intriguing possibilities. The aim of tissue engineering is to create living, three-dimensional tissue/organs using cells obtained from readily available sources, and like cells obtained directly from the patient.⁵⁴ The ultimate target of the previous works was to grow specific cells to a particular organ then directing the cell growth to form the actual organ. Theoretically, this can be done through the attachment of specific cells to a scaffolding biopolymers and biocomposites matrix that directs cell differentiation, attachment, and growth. In order to apply this amazing material, a physical scaffold is required to allow the organization of cells to form the specific organ.

Recently, considerable interest in using of biopolymers and biocomposites hydrogels as leading candidates for engineered tissue scaffolds owing to their structural similarities, and unique compositional to the natural extracellular matrix, in addition to their desirable framework for cellular survival, and proliferation. Moreover, the ability to control the porosity, surface, shape, sizes of hydrogel scaffolds, and morphology have been used to create new opportunities to overcome various challenges in tissue engineering such as tissue architecture simultaneous seeding, and vascularization of multiple cells. Special attention was given to the various design considerations for an efficient hydrogel scaffold in tissue engineering. Also, some challenges associated with the use of hydrogel scaffolds were reported.⁵⁵

These scaffolds need to interact with the cells through specific bio-reactions that control growth factor, and cell adhesion responses. The scaffolds are ideally biodegradable. Some important studies in this area have recently been reported⁵⁶ where the use of biodegradable biopolymers and biocomposites hydrogels as a temporary support template for cartilage. Cartilage is a biphasic material made up of collagen as the solid support suspended in a gel of proteoglycans. The chondrocytes within this gel are responsible for maintaining the extracellular matrix of cartilage (glycosaminoglycans and type II collagen).

Scaffold made from calcium alginate hydrogel was prepared by dissolving alginate in water and adding calcium ions to form a complex crosslink hydrogel network. The immobilization of chondrocytes in alginate hydrogel was done simply by soaking the alginate hydrogel in a chondrocytes solution. Researchers have trported that the chondrocytes maintained within their structure, were able to proliferating at rates significantly higher than those of mono-layer cultures. It can form a mechanically functional matrix in a hydrogel network, and maintained their production of glycosaminoglycans collagen. This led to the first successful methods that have shown a new cartilage which can be created in vivo using hydrogel scaffolding.

In addition, Malafaya et al., 2007 reported⁵⁷ the designing of biodegradable biopolymers and biocomposites hydrogels for bone regeneration through growth factor release. In this research study, the gelatine was crosslinked with either carbodiimide or glutaraldehyde. The growth factor of the preformed gelatine hydrogels was added by solution adsorption. The cationic growth factor was held in the gelatine matrix by complexation with the anionic sites along the gelatine backbone. The gelatine was found to be enzymatically degraded in the body to release the growth factor. When implanted into a bone defect, the growth factor resulted in accelerated bone regeneration and repairing the bone defect.

An ideal scaffold for tissue engineering is collagen which considered by many researchers due to its major protein component of the extracellular matrix. It provides support to connective tissues for cartilage, bones, skin, tendons, ligaments, and blood vessels.^58–62 In its natural environment, collagen interacts with cells in connective tissues and transduces essential signals for the regulation of cell anchorage, proliferation, migration, survival and differentiation.⁶³

Gelatin is a natural polymer derived from collagen and commonly applied in medical and pharmaceutical applications owing to its biocompatibility, and biodegradability in physiological environments.^64,65 These special characteristics of gelatin contributed gelatin as safe component sealant for vascular prostheses or in drug formulation.⁶⁶ In addition, gelatin characterized by low antigenicity due to its animal origin. Gelatin contains a large number of glycine, proline, and 4-hydroxyproline residues.

The use of gelatin as a carrier for cell delivery which consider being promising technology for tissue engineering applications. Several examples which include human chondrocytes, and bovine,^67,68 mesenchymal stem cells,⁶⁹ and human preadipocytes.⁷⁰

Degradable tubes based on natural polymers such as collagen biopolymer used in synthesis of a Nerve Trunk was reported⁷¹ by Yannas et al. 2015.

Other polysaccharides such as agarose, carrageenans and gellan gum which named as cold set gels that is formed by gel cooling solution have been investigated for application in tissue engineering.⁷² They have been studied in some drug delivery systems for tissue engineering but they are still narrow potential applications.

Carrageenans are sulfated polysaccharides that are widely used in industry. They are extracted from red marine algae and because they can form reasonably stiff and thermo-reversible gels in the presence of so called gel promoting salts at room temperature.⁷³ Carrageenans are linear polymers consisting of (1 → 4)-linked α-D-galactose units chains and of (1→3)-linked β-D-galactose which are substituted and cured to the 3,6-anhydro derivative, which depend on the source and extraction conditions.⁷⁴

Dextran is a high molecular weight natural polymer composed of highly branched D-glucose. It is produced by different bacterial strains from sucrose via the action of dextransucrase enzyme.⁷⁵ It is consisting of α(1→6)-linked D-glucose residues with some degree of branching via α(1→3) linkages. Dextran is biodegradable and biocompatible and has a wide range of molecular weights along with several derivatives.

Gellan gum is a high molecular weight microbial exo-polysaccharide produced by Pseudomonas elodea. It consisted of linear anionic heteropolysaccharide composed of the tetrasaccharide (1→4)-L-rhamnose-α(1→3)-D-glucose-β(1→4)-D-glucuronic acid-β(1→4)-D-glucose as repeating unit, with side carboxylic groups. The gellan gum is widely used in food industry due to its ability to form transparent gels which is resistant to acid and heat in compared to other polysaccharide gels.

Biosensors

Biosensors are probe or a compact device that detects, records, and transmits information regarding and related to physiological change or detects the presence of various biological materials such as antibody and enzyme or presence of chemical materials in the environment. A biosensor probe integrates these biological component or chemical materials with an electronic component to yield a measurable response. Moreover, biosensors are used to detect changes in the physiological change in the environment. The main aim of the biosensor is to produce either continuous or discrete electronic signals which are proportional to a related group of analyte or single analyte.⁷⁶

In addition, the biosensors comprise a bio-sensing element, a signal a data processor, conditioner, a signal generator, transducer, and one or more organic or inorganic membranes.⁷⁷

One of the early disadvantages of these bilayer probes was their poor ion diffusion characteristic. Hydrogels were successfully used to provide both the required ion diffusion and also the support for the thin lipid bilayer membrane.⁷⁸

Hydrogels made from natural origin have been used as reactive matrix membranes in biosensors. Hydrogels possess several advantages over other polymers that they exhibit selective and rapid diffusion characteristics of the analyte, as well as provide support. For example, they show remarkable success in the area of lipid bi-layer based biosensor membranes but one of the early disadvantages of these bi-layer probes is their poor ion-diffusion characteristic. Hydrogels were successfully used to provide support for the thin lipid bi-layer membrane and also required ion diffusion.⁶⁸

Hsu et al., 2020 reported⁷⁹ that the diabetes mellitus become a serious non-communicable disease in worldwide. According to World Health Organization (WHO), there were 422 million diabetes patients in 2014 and this number is expected to increase to 592 million by 2035.

The most attention of the various types of biosensors, that measure glucose.⁸⁰ In these biosensors, the formation of hydrogen peroxide or the consumption of oxygen is monitored where the enzyme glucose oxidase catalyzes the reaction of glucose and oxygen to form gluconic acid and hydrogen peroxide. Hydrogels are used as enzyme immobilization polymer in these types of biosensors.

The detection technology of glucose should provide selectivity, high sensitivity, and reliability which has been intensively studied and attracted a lot of attention in biomedical science and food industry.⁸¹ have developed nano-biocomposites hydrogel which made of poly-glutamic acid (PGA) and chitosan, that can entraps both glucose oxidase (GOx) and magnetic nanoparticles (MNPs) within the hydrogel composite matrix as shown in Figure 2.

Figure 2.

Preparation of PGA/chitosan/GOx/MNPs hydrogel.

The electro-deposition of a 3-aminopropyltriethoxysilane-chitosan (APTES-CS) hybrid gel composite film for in situ immobilization of glucose oxidase (GOx) on an Au or platinized Au (Ptnano/Au) electrode for bio-sensing of glucose was reported⁸² by Lei et al., 2011.

Portable biosensors are small, wearable devices similar in size and appearance to a wristwatch that continuously monitor various physiologic parameters of the wearer.⁸³ Biosensors designed for research applications commonly measure surrogate markers for sympathetic nervous system activity, namely electrodermal activity (EDA), skin temperature, and locomotion. Similar devices have been utilized to monitor multiple physiologic and pathophysiologic conditions known to involve robust SNS changes such as stress, post-traumatic stress disorder (PTSD), and epilepsy. They have also been applied to compliance monitoring for drug adherence and suicide risk and are able to detect cocaine use in natural environments.⁸³

Different biomedical applications of natural based hydrogels prepared by gamma radiation

The applications of natural based hydrogels or biohydrogels which prepared by gamma radiation and applied in biomedical field^84–89 are summarized as shown in Figure 3. Biopolymers and biocomposites can be obtained by radiation technique and more frequently methods using irradiation are investigated.^90–92 The synthesis of hydrogels by gamma ray irradiation is a wide convenient method for biomedical applications and this technique led to formation of sterile, non-contaminated hydrogels. The properties of the hydrogels were enhanced by blending of natural polymer such starch, chitin, chitosan…etc. with the petroleum origin hydrogels to form biohydrogels. Moreover, the degree of cross-linking, which strongly affect the extent of swelling of the hydrogels, can be easily controlled by changing the irradiation dose. Biopolymers and biocomposites hydrogels extracted from natural polymers mimic many of the characteristics of extracellular matrices, thus potentially guiding cell migration and growth and tissue in the process of organized system regeneration as well as wound curing, and have the potential to stabilize encapsulation and transplantation of cells. These biohydrogels namely biopolymers and polymeric composites which prepared by gamma radiation has been used in various biomedical fields as shown in Figure 3 owing to its biocompatibility non-toxicity, and biodegradability as described in details in this review.

Figure 3.

Different applications of natural based hydrogels prepared by gamma radiation in biomedical fields.

Also, biopolymers and biocomposites hydrogels varied in function, and shape. In particular, because of their unique advantages of in situ drug delivery applications, injectable hydrogels have considerable interest as carriers for topical and drug delivery owing to advantages such as a minimally sustained invasive administration procedure, and good syringe ability.

Advantages of radiation processing of natural based biopolymers and biocomposites hydrogels

1. Simultaneous polymer modification by crosslinking and sterilization which reduces costs and simplifies the process.

2. Controlled crosslinking which is important for wound care management, where the main advantage of hydrogels dressings are reducing the pain, its tender contact with nerves points, so softer surfaces can achieve this effect much better.

3. Biopolymers and biocomposites designed to slow release of drugs which is sometimes important.

4. Physical properties can easy control to produce elastic or solid ones and fluid hydrogels.

The biopolymers and biocomposites hydrogel dressing is commercially successful dressing that can be prepared by radiation technology in the form of thin, swollen slides of hydrogel.⁹³ The steps of this technique are shown in Figure 4.

Figure 4.

Production of hydrogel wound dressings by radiation technology.

Temperature and pH responsive hydrogels, which prepared by gamma irradiation technique and based on chitosan grafted with AAc, HPMA, PVA and gelatin, for controlled release of oxttetracycline.⁸⁴ This study of grafted chitosan and gelatin based hydrogel indicated the most preferable hydrogel for drug release is that of (AAc/PVA)-g- chitosan prepared at low irradiation dose which show temperature responsive hydrogel compared to other systems. These hydrogels were applied as successful application for controlled oxttetracycline delivery hydrogel that used for treating infections on the respiratory gonorrhea, skin, and tracts.

Gamma radiation synrthesis of Poly (starch/acrylic acid) pH-sensitive hydrogel for controlled release of rutin were investigated⁹⁴ by Abdel Ghaffar et al., 2016. The Poly (starch/acrylic acid) was found to be a pivotal anti-inflammatory approach for patients with Inflammatory bowel disease in order to reduce toxicity, and increase efficacy.

Ismail et al. 2009 immobilized⁹⁵ α-Amylase onto chitosan/alginate copolymer and on the N- isopropyl acrylamide, and alginate copolymer by entrapment method. The optimum stability and pH of the immobilization enzymes found to be more stable due to the diffusion limitations. The efficiency of reuse of the immobilized and free enzymes showed a negligible decrease in the relative activity of these enzymes after being used for 12 times.

Storage of the free and immobilized α-amylase enzymes in dry solid for 2 months showed that the free α-amylase lost most of its catalytic activity after their storage. Also, the storage of the immobilized enzymes in dry system was much better than that in the wet system due to the prevention of out digestion and thermal degradation. Storage of immobilized and the free α-amylase enzyme at room temperature showed much less stability than that of the immobilized enzyme in 4°C.

For many years the immobilization of enzymes in biopolymers and biocomposites hydrogels are an attractive process in enzyme technology which have played important role in biomedical applications. Various techniques which include covalent bonding, adsorption, and entrapment have been investigated.⁹⁶

Injectable biohydrogels have the advantage of being non-invasive and regulating the geometry of the hydrogel formed in situ compared to preformed hydrogels that require surgical implantation into the body. Injectable biopolymers and polymeric composites offer several advantages over traditional injectable materials:

1. Having three dimensional matrixes network structures

2. Characterized by controlled release of therapeutic agents

3. Forming a functional micro-environment for tissue regeneration

4. Being stress-free and monitorable. Injectable biomaterials can bind to a variety of nucleic acids, cells and growth factors, allowing these substances to be preferably encapsulated, retained and delivered to the target site.^83–88

Conclusion

Radiation technique has many and wide advantages, namely, it is clean, simple, efficient, and environmentally friendly process in synthesis of different biopolymers and biocomposite polymers. It used for synthesis, modification and sterilization in a single technological step which reduces costs and production time. Natural polymers hydrogels and composites can be used as alternative to the petrochemical origin plastics. The use of radiation technique in preparation of biomedical polymer hydrogels and composites are growing rapidly in drug delivery systems, wound dressing, injectable materials, tissue engineering, immobilized enzymes and biosensors as shown in this review.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethical Approval

Not applicable because it is a review article that collect and present recent researchers articles in simple way which show that the radiation technique is the combining of preparation and sterilization in a one technological step thus, reducing time of the production and lower the costs. The use of gamma radiation technique in biomedical application is growing rapidly in controlled drug delivery, injectable materials, wound dressing, tissue engineering, immobilized enzymes and biosensors as shown in this review.

ORCID iD

Ashraf Maher Abdel-Ghaffar

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