Vitamin E was first discovered and described by Evans and Bishop in 1922; it includes eight natural forms (α, β, γ, δ; tocopherols and tocotrienols), and it can be found in various products bearing fats of both vegetable and animal origin, such as in olive or almond oil, hazelnuts, and egg yolk, and in the liver. Basically, tocopherols and tocotrienols have the same chemical structure, characterized by a 16-carbon lateral chain attached to position 2 of a benzopyran ring. The two isoforms differ substantially from the saturation of the long radical chain: tocopherols have a fully saturated chain, while tocotrienols have an unsaturated chain. As Figure 1 explains, the two homologs were named according to the position and number of the methyl group bound to the phenolic ring ^[1][2][3][1,2,3].

Among all the isoforms of vitamin E, α-tocopherol is the most abundant in the blood, because it is the only one that is absorbed within the body, while the other isoforms are excreted through the intestine. The liver, which takes up nutrients after they are absorbed by the small intestine, absorbs vitamin E thanks to the plasmatic lipoproteins that function as carriers. Among all the various forms of the vitamin E, alpha-tocopherol is re-secreted through the liver protein of α-tocopherol transfer (α-TTP) and distributed to circulating lipoproteins (LDL, IDL, VLDL). The other forms are metabolized and then expelled through the intestine (Figure 2) [4].

Alpha-tocopherol is a phenolic antioxidant. The scavenging mechanism involves the donation of hydrogen from the hydroxyl group (-OH) of the phenolic ring to free radicals (ROS). In this way, the free radicals become unreactive and unable to do any more damage. After this reaction, also the phenolic compound itself becomes relatively unreactive with a higher stability. Its stability is guaranteed by the now unpaired electron which is on the oxygen atom and which is delocalized in the structure of the aromatic ring. α-tocopherol is located within the phospholipid membrane of the cell, and it occurs with the radical chain embedded in the hydrophobic core of the double layer [5]. Its concentration, compared to the lipids present in the membrane, is very low, but in spite of this, it plays an important role in preserving the integrity of the membrane by preventing lipid peroxidation which causes damage of cellular membranes, lipoproteins, and other molecules that contain lipids, in conditions of oxidative stress ^[1][6][7][1,6,7].

Oxidative stress is a pathological condition caused by the imbalance between the generation and elimination of chemical oxidant species (ROS), and it is involved in several neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease that are implicated in free radical processes and oxidative damage [8]. That said, it is easy to think of vitamin E that, thanks to its important qualities as an antioxidant, may have an important role in the integrity of the brain. To confirm this, a high level of α-TTP was found in the brain [9].

Vitamin E is an important anti-inflammatory molecule since it acts on many different factors that affect, directly or indirectly, the immune system. Vitamin E is able to modulate inflammation through different ways: it has effect on proinflammatory enzymes such as COX, responsible for prostaglandins (PG)E₂ production ^[10][11][10,11]; (PG)E2 is a proinflammatory mediator that has been associated with several senility-related diseases such as cancer, arthritis, and cardiovascular diseases ^[4][7][12][4,7,12]). It modulates the proliferation and activation of certain cells of the immune system such as T cells, lymphocytes, and NK cells [13]. Finally, it acts on the secretion of proinflammatory cytokines such as IL-6 and TNF-α. Thanks to these factors, vitamin E plays an important role in helping to prevent chronic inflammation ^[11][13][11,13]. Chronic inflammation is strictly linked to oxidative stress [14] and, together with it, it is the main cause of age-related disease and cancer [11].

Vitamin E has also an important role in the inhibition of platelet aggregation, inhibiting various enzymes such as PKC, which is a key signal transduction pathway in several cell types ^[1][15][1,15]. α-tocopherol, thanks to its free-radical scavenging and anti-inflammatory properties, has a benefit also in dermatology: it protects the skin from UV radiation, and accelerates the wound healing process after an injury such as ulcers or burns [16]. Inflammation could be associated also to a large number of different phenomena related to bone health: it is thought that thanks to its anti-inflammatory action and regulation of cytokine secretion, vitamin E can influence bone remodelling, being able to protect the bone against osteoclastic activity, increasing osteoblasts differentiation, and protecting cartilage health ^[17][18][19][17,18,19]. In addition, recent studies have shown that vitamin E also has biomechanical effects, being able to increase specific characteristics such as load and yield [20]. Together with all these considerations, vitamin E, due to its antioxidant function, role in anti-inflammatory processes, inhibition of platelet aggregation, and immune system-enhancing activity ^[1][9][1,9], brings a wide range of benefits, from anti-cancer effects [21] to the prevention of disease progression, and in improving quality of life in the elderly [22]. The figure below (Figure 3) shows a schematic representation of the biological role of vitamin E.

More controversial and still under study, is the anti-bacterial role of vitamin E. In the literature, it is possible to find vitamin E used as a natural compound to treat infections caused by specific Gram-positive or negative bacteria ^[23][24][23,24] or as an antibiotic adjuvant used in combination with antibiotics for the treatment of infections ^[25][26][25,26]. Moreover, the addition of vitamin E to materials may have the ability to reduce biofilm formation on the surface. As the literature suggests, it is possible to believe that tocopherol is able to reduce the biofilm formation capacity of a big range of strains (S. aureus and S. epidermidis, etc.), regardless of the classification of the bacterium (Gram-negative or -positive) [27]. This, however, comes into opposition with other studies that show instead that vitamin E, in composition with other materials, did not reduce biofilm formation [28].

Once the biological role of vitamin E is understood, it is certainly interesting to analyse its application and detection methods, when it is combined to a biomaterial. Over the past 20 years, there has been a strong increase in interest in scientific research on α-tocopherol combined with various biomaterials (Figure 4). This review selected about 100 reviews best suited to the topic discussed.