To minimize the risk of exposure to cross-infection between patients and healthcare workers, it is necessary to use personal protective equipment (PPE) such as disposable medical gloves, masks, or gowns [
1]. Among these items, medical gloves were widely used by the population during the COVID-19 pandemic and played a key role as an infection-prevention tool for medical staff and society in general. Microorganisms, infectious agents, and pathogens, such as bacteria, viruses, fungi, protozoa, and prions, live in the human body and the surrounding environment [
2]. Most of these organisms do not pose a threat to the general population, but during an epidemic or in medical facilities, pathogenic microorganisms can be present at serious levels and cause illness. Hands are a major source of infection spread. Although hand washing is effective in eliminating most microorganisms, there are circumstances in which this practice is not sufficient, and exposure justifies the use of an additional layer of protection. For these reasons, medical gloves are mandatory when performing invasive procedures or coming into contact with sterile sites [
3].
According to World Health Organization (WHO) recommendations, protective gloves should always be used in cases of contact with blood, mucous membranes, injured skin, or other potentially infectious material, as well as against hazardous chemicals and drugs [
1]. The aim of this work is to review the materials used in medical gloves due to their importance as an element of personal protection. The purpose is to compare the natural and synthetic rubbers used in their manufacture as well as identify smart materials that can be added to medical glove formulations to improve their performance and properties. These smart materials include biopolymers, eco-friendly additives, bio-based fillers, and antimicrobial agents [
4]. Similarly, several prototypes of medical gloves, blends, composites, and coatings made from these smart materials are intended to be addressed.
1.1. History of medical gloves
Many healthcare professionals, even before the microbial nature of infection had been established in the mid-19th century, knew that accidental open injuries during their work could lead to an infected wound, illness, and possibly death [
5].The exact time when protective gloves were first employed in the healthcare business is unknown. There are suggestions that an obstetrician called Walbaum covered his hands with sheep intestine as early as 1758 [
6]. Other physicians used to cover their hands with cotton, silk, or leather gloves [
5].
An important milestone in this field was the discovery of vulcanization by Charles Goodyear in 1839, when he was working at a rubber factory in Massachusetts and mixed a piece of rubber with sulfur on a hot stove [
7,
8]. He had discovered the vulcanization process, which turned natural rubber (NR) from a thermoplastic that could be softened by heat into a harder, more stable, and more durable product. Vulcanization consists of the development of a crosslinked rubber that is the product of the creation of bonds at several points of the individual NR chainlike molecules using sulfur as the crosslinking agent [
9,
10].
Vulcanized rubber quickly became the choice for coarse protective medical gloves. William Halsted of Johns Hopkins Hospital in Baltimore was likely one of the early promoters of sterile NR gloves in the operating room, but it is uncertain who initially encouraged their use. Halsted asked the Goodrich Rubber Company to make thinner, and less rudimentary NR gloves, although they were still quite stiff and unwieldy. Over time, the NR glove became even thinner and shorter. In 1897, the first article about sterile NR gloves in medicals settings came out. This paper, entitled “Rubber gloves in the practice of surgery,” was written by Werner von Manteuffel and appeared in a German surgical journal [
11]. By the beginning of the 20th century, the use of sterile NR gloves had become widespread in surgical practice [
5].
1.2. Market of medical gloves
The rising incidence of epidemic diseases such as swine flu (H1N1) and the more recent and widespread COVID-19 (SARS-CoV-2) has driven the growth of the global medical glove market. As reported by the Financial Times, during the latter pandemic, glove industry sales and profits increased by over 100% [
12,
13]. According to data provided by Global Market Insights, the worldwide market of medical gloves grew dramatically as a result of the first phase of the COVID-19 pandemic expansion, reaching over
$14 billion in 2020 [
14]. In 2021, when the infection was best understood and the supply of these products increased in line with demand, this market experienced a slight decline in profits and reached
$12.31 billion in value. Nevertheless, it is expected to expand at a compound annual growth rate (CAGR) of 5.8% from 2022 to 2030 [
15].
Figure 1 shows EU-27 imports of medical gloves between January 2019 and December 2021. The graph was compiled from Eurostat dataset “DS-1180622” for product codes: “B3-40151100 Surgical gloves, of vulcanized rubber other than hard rubber (excl. fingerstalls)”; “B3-40151900 Gloves, mittens, and mitts, of vulcanized rubber (excl. surgical gloves)” and “B4-39262000 Articles of apparel and clothing accessories produced by the stitching or sticking together of plastic sheeting, including gloves, mittens, and mitts.” In the graph, the business as usual (BAU) trend line was plotted using import data from January 2019 to March 2020, when the WHO proclaimed the global pandemic of COVID-19. To estimate the rise in medical glove imports during the COVID-19 pandemic, the over BAU value was estimated using data from April 2020 to August 2021. The value of net imports in excess of BAU was approximately 340 000 tonnes [
16].
MARGMA (Malaysian Rubber Glove Manufacturers Association) estimates that the global demand for gloves grew by almost 200 billion units in the first months of 2020 due to the COVID-19 pandemic [
17]. In 2021, at the peak of this pandemic, the global demand for rubber gloves reached 492 billion units. The exports of rubber gloves from Malaysia in monetary value terms from 2014 to 2021 are illustrated in
Figure 2. This graph clearly reflects the significant growth that has occurred. Prior to the epidemic, the value of exports did not exceed RM20 billion; however, by 2020, exports had reached RM35.26 billion, and by 2021, they peaked at around RM54.81 billion [
18].
Major players in the gloves market include Top Glove and Comfort Gloves [
19].
Figure 3 shows the quarterly financial report of Top Glove Corporation Berhad with its earnings during the past pandemic period. In first quarter of 2021 (1Q-2021), this company achieved its highest quarterly net profit of RM2.38 billion, and a high revenue of RM4.76 billion. The group’s quarterly net profit, compared to the previous quarter (4Q-2020), increased 84% from RM1.292 billion, while revenue increased 53% from RM3.11 billion [
20,
21].
The quarterly financial report of Comfort Gloves Berhad is presented in
Figure 4. This chart shows the revenue increased from RM138.65 million in 1Q-2020 (before COVID-19) to RM541.24 million in 2Q-2021, which represents a rise of 290%. In the same quarters, the group net profit amounts were RM10.24 million and RM219.13 million, respectively, which means an increase of 2040% [
17,
22,
23].
In terms of medical gloves material market, natural rubber (NR) and acrylonitrile butadiene rubber (NBR) gloves are the most important sectors. NR gloves are the type that generates the highest revenues, due to their variety of applications in fields such as examinations and surgeries in the medical environment and as protection against chemicals and pathogens in the general industrial sector [
24]. In 2020 market share, the NR examination gloves segment accounted for
$5.1 billion, while the surgical gloves segment reported
$4 billion [
14]. In 2021, the global NBR gloves market was valued at
$8.54 billion, and its size is expected to expand at a CAGR of 10.54% from 2022 to 2029. The NBR gloves market attracted substantial new investments due to price incentives and increased demand resulting from the COVID-19 outbreak [
25].
1.3. Production process of medical gloves
The most common natural and synthetic rubber medical gloves are produced by the dipping process (
Figure 5). Slowly, hand-shaped porcelain or metal molds are immersed in various tanks and subjected to different treatments. The main one is the dipping in the compounded latex, which consists of a mixture of natural or synthetic latex and compounding chemicals [
26]. The compounding chemicals are the additives that must be included in medical gloves formulations to achieve the required characteristics, such as mechanical strength, barrier integrity, color, aging protection, etc. [
27]. These additives include vulcanizing agents, plasticizers, softeners, fillers, antioxidants, stabilizers, and different chemical compounds intended to improve processability [
28,
29].
The steps of the dipping process are briefly described below:
Former Cleaning: The procedure begins with washing and drying the hand-shaped molds. Alkaline solutions, acidic solutions, oxidizing agents, surfactants, and combinations of these can be employed as cleaning agents [
28].
Coagulant Dipping: After cleaning the formers, they are coated with a coagulant, which is usually a polyvalent metal salt, an organic acid, or an organic acid salt [
28]. The formers are dipped into the coagulant bath to promote adhesion and distribution of the compounded latex. The coagulant solution may also contain a separating agent, often calcium carbonate, which prevents the rubber from adhering to the molds. Subsequently, molds are subjected to a drying process [
26].
Latex Dipping: Next, the glove formers are dipped in a tank containing the compounded latex. The latter is a mixture of the rubber suspension with several substances needed to form a glove known as compounding chemicals. Formerly, the term “latex” refers to the white, milky sap gathered from the rubber tree; however, the terminology has also come to refer to dispersions of fine rubber particles in a liquid composed predominantly of water. Natural rubber (NR), polyisoprene rubber (IR), acrylonitrile butadiene rubber (NBR), and chloroprene rubber (CR) are mainly used in the dipping process [
26].
Before adding other chemicals to commercial latexes, they must be stabilized to avoid alterations and variations in their ionic strength during the manufacturing process. The formulation ingredients must be integrated directly into an aqueous dispersion due to their insolubility. For proper stabilization of the latex, the introduction of chemicals such as surfactants and rosin resins are required.
Table 1 presents some chemicals used for latex stabilization and their function [
27].
Once the latex has been adequately stabilized, crosslinking agents are usually applied to bind the polymeric chains together and form a three-dimensional network that gives the material the desired flexibility and performance [
27]. The crosslinking process may involve the use of several crosslinking agents.
Vulcanization, in which crosslinking is carried out by means of sulfur bond, is the most common technique [
8]. Colloidal sulfur is often employed with NR, IR, and NBR latexes. Typically, 0.5 to 2.5 parts per hundred of rubber (phr) are used. Zinc oxide is utilized in the range of 4.0-5.0 phr for CR [
26]. Carbamates in conjunction with thiazoles are ultra-fast accelerators for the crosslinking process. The latex mixture can alternatively be vulcanized by adding sulfur donors such thiurams and the thioureas as activators. Guanidines, or xanthates, also can be added [
30].
Fillers, in particular calcium carbonate, are commonly used to reduce the cost of NR examination gloves [
27]. The degree of reinforcement offered by a filler for a rubber glove depends on many aspects. The most crucial aspect is to achieve a large filler-rubber interface which only colloidal filler particles can offer. To avoid dispersibility and processability concerns, the particles must have a specific surface area between 6 and 400 m
2/cm
3 [
31].
Medical gloves contain antioxidants that defend them against attack by oxygen while in storage. Surgical and examination gloves contain non-staining antioxidants such as phenolic antioxidants (styrenated and hindered phenols), which are sometimes combined with a secondary antioxidant [
30].
Pigments and dyes are combined with gloves to achieve opacification and impart the desired hue to the product [
27]. The use of pigments or UV absorbers can improve light fastness to prevent hardening of NR gloves when exposed to direct sunlight. Also, by adding so-called antiozonants, protection against ozone can be accomplished [
30].
Pre-curing: After the latex dipping process, another drying phase takes place. In this stage the curing process is partially carried out, which is called the pre-curing process. The compounded latex that has been deposited on the molds is allowed to acquire a certain wet gel strength before leaching step [
28].
Leaching: This stage is often referred to as “wet gel leaching.” Once the latex mixture has dried, residual chemicals and proteins on the gloves surface are removed by immersion in tanks of hot water. The tanks are refilled periodically with hot and fresh water [
28]. The water immersion period ranges from 1 to 10 min, depending on the film thickness. Washing the NR latex film in a weak aqueous alkaline solution, such as aqueous ammonia or aqueous potassium hydroxide solution, facilitates protein removal [
26].
Curing: This process, also simply referred to as vulcanization, often involves a hot air circulation blower. The minimum vulcanization temperature varies depending on the compounded latex. Normal ranges for NR and IR are 90-100 °C, for NBR 120-140 °C, and for CR 120-130 °C [
26]. The rubber reaches its final strength upon leaving the vulcanization oven [
28].
Surface treatment: The purpose of the treatment of the inner surface of gloves is to prevent sticking together, to facilitate donning, to ensure a smooth fit, and to provide comfort during use. Traditionally, powder was employed for this purpose. However, powder was associated with increased risks of irritation or hypersensitivity for both users and patients, especially when it is used NR gloves. NR latex proteins, which cause allergies, adhere to the powder, and spread rapidly in the environment, increasing the prevalence of allergies. As a result, the use of powder is increasingly restricted by regulation. In several countries, such as the United States, Germany, and the United Kingdom, powder is prohibited [
27,
32]. As an alternative, other treatments can be applied, such as chlorination, and polymeric coatings [
33].
Powdered gloves are formed by dipping them in a slurry. This substance is also known as wet powder which contains talc, silica, or crosslinked starch. For the chlorination process, the gloves are dipped in a solution containing chlorine. The reaction with the chlorine forms a very thin layer of chlorinated rubber on the surface of the glove. The chlorine solution is generated by pumping chlorine gas directly into water or by combining hydrochloric acid with sodium hypochlorite [
26]. Probably the most widely used method for producing powder-free NR gloves is chlorination. The double bonds of the polymer chains present in NR are highly prone to the addition of chlorine which has the effect of stiffening and detackifying the rubber surface of the glove [
28].
Regarding to polymer coating, it is common practice to dip gloves in hydrogel, an aqueous dispersion based on acrylic or polyurethane diluted to the required concentration, silicone polymer, or a polymer blend [
26]. Coatings can be classified into two categories: hydrogels and non-hydrogels. Hydrogel coatings are composed of substances that absorb water several times their weight, swell and become slick so that gloves can be easily donned. Non-hydrogels are water-repellent, and the coating’s topology matches the features of a powdered surface. Often, a dual strategy is employed: First, the donning side of the glove is coated, and then the grip side is chlorinated [
28].
1.4. Environmental concerns related to medical gloves
The global demand for rubber gloves keeps increasing despite the environmental problems related to their disposal [
34]. Rubber gloves account for 24% of total medical solid waste [
35]. Discarded NR gloves typically take at least two years to degrade in a natural environment. Many highly additivated and crosslinked commercial NR gloves require even longer to fully decompose in soil under ambient conditions [
36].
The various stages of rubber gloves production require multiple resources, including potable water, chemicals, energy, and electricity. Water is often used for the preparation of the compounded latex, as well as for cleaning, leaching, and cooling procedures. Heat is utilized in the drying and curing processes. Electricity is mainly used for lighting, pumping water, operating heavy machinery, and wastewater treatment [
37].
At each stage of the glove manufacturing process, there are material inflows and waste outflows. Contaminated rinse water flows can be said to occur throughout the washing and leaching stages. In operations involving heating or mechanical action, energy is consumed. Ovens fueled by liquefied petroleum gas (LPG) produce carbon dioxide emissions as well as energy losses. Gloves and packaging materials are also discarded downstream in the production process. This manufacturing technique has an impact on the environment and human health [
38].
It is important to note that sulfur is one of the most widely used crosslinking agents. The sulfur-based curing system (vulcanization) is harmful from the point of view of environmental and health problems. The emission of toxic sulfur-based gases can cause acid rain, which returns considerable quantities of sulfuric acid to the earth, destroying vegetation and degrading soil quality. In addition, gaseous sulfur compounds can induce irritation and inflammation of the respiratory system. Higher levels of sulfur dioxide can cause eye burns and be fatal to humans [
39]. In addition, accelerators such as benzothiazoles, which are toxic to aquatic life, are used in the vulcanization process [
40].
To counterbalance the disadvantages of the traditional sulfur process, alternative curing methods include metal ionic crosslinkers, organic peroxides or physical methods such as UV and gamma rays. The basic mechanism underlying the functionality of the metal ion as a crosslinker is related to its charges. Sulfur forms covalent bonds between elastomer chains in vulcanization and these sulfur bonds can be replaced by an ionic bond with a multivalent metal ion, resulting in a reduction of process time and energy consumption. The most common applications of metal ion crosslinking are NBR and CR gloves. As this method does not require initiator or crosslinking accelerator, the cost of materials is reduced [
39].
In the ultraviolet (UV) crosslinking, covalent bonds are accomplished via the UV-assisted thiol-ene reaction, which represents a versatile and innovative procedure for the crosslinking of NR. It can be produced at room temperature with short process times and without the use of hazardous chemicals. UV-crosslinked NR articles exhibit good skin compatibility and high tensile strength. Both the lattice density and Young’s modulus have been found to increase with radiation intensity [
41].
With respect to gamma ray crosslinking, research has shown that a carboxylated NBR can be covalently crosslinked by high-energy radiation, such as gamma rays or electron beam [
41]. The advantages of this procedure include the absence of hazardous chemical residues, full control of the crosslink density and improved mechanical properties of the crosslinked material. Disadvantages include the large amount of energy required for the process, the fact that direct exposure of humans could cause cancer and the lack of available technical data [
42].
In recent years, the widespread usage of rubber and the resulting large amount of waste of this material has increased interest in this field with the objective of applying bioremediation. NR can be degraded by bacteria and fungi, but the process is slow and even slower in gloves with higher crosslink densities [
35,
43]. Linos
et al., (2000) found that
Pseudomonas aeruginosa AL98, gram-negative bacteria, was capable of disintegrating NR, either in its raw form as NR latex concentrates or in its vulcanized forms as NR or IR gloves [
44].
Although the biodegradation of NR has been widely investigated, progress in this field of study has been hampered by the difficult isolation of appropriate bacteria, extended cultivation periods, and the scarcity of genetic tools [
45].
Actinomycetes have dominated the literature about the breakdown of
cis-1,4-polyisoprene among NR-degrading bacteria. The most prominent genera are
Streptomyces,
Mycobacterium,
Nocardia, and
Gordonia [
46]. The three latter species directly attack the NR substrate, producing a biofilm and fusing with the polymer to induce cell surface degradation. The adherent group of bacteria has been implicated as much more efficient degraders of this substance than enzyme-secreting strains [
47].
There is evidence that some NR glove additives limit microbial breakdown action. It has been demonstrated that the extraction of these inhibitory substances (antioxidants) using organic solvents promotes the colonization of
Gordonia and
Micromonospora species. However, using chemical solvents to remove rubber inhibitors is not environmentally friendly, so an alternative by microbial action was studied. Due to the similarities between rubber additives and fungal degradable chemicals, the successful breakdown of antioxidants by white rot fungus has been reported [
46].
An example of a plant for recycling and remediation of NR by microbial action is shown in
Figure 6. The waste NR is ground to promote further microbial attack. The ground rubber is then heated to denature the unstable compounds, while sterilizing the rubber to ensure the absence of pathogenic microorganisms that could inactivate or compete with the microorganisms used in the bioreactors [
46].
After heating, a detoxification process is performed in which white rot fungi can be used to degrade the NR additives. Once the additives have been removed, a devulcanization process is performed with
Thiobacillus ferrooxidans to break the sulfur bonds of the NR. The decomposition can be completed with potent degrader agents such as
Nocardia sp. and
Gordonia polyisoprenivorans. Then, the lower molecular weight compounds can be catabolized by
Streptomyces sp. or Xanthomonas sp. Alternatively, the devulcanised NR can be filtered, washed, dried, and combined with fresh NR for reuse [
46].