Acrylic-based polymers have been used for many years in biomedical applications because of their versatile properties. Many different polymers belong to this class of polymers, of which a significant number have been approved by the US Food and Drug Administration (FDA) and are frequently used in ophthalmologic devices, orthopaedics, tissue engineering applications and dental applications. The applications of this class of polymers have the potential to be expanded exponentially in the biomedical industry if their properties such as mechanical performance, electrical and/or thermal properties, fluid diffusion, biological behaviour, antimicrobial capacity and porosity can be tailored to specific requirements. Thus, acrylic-based materials have been produced as multicomponent polymeric platforms as interpenetrating polymer networks or in combination with other sophisticated materials such as fibres, nanofibres, carbon nanomaterials such as graphene and its derivatives and/or many other types of nanoparticles in the form of composite or nanocomposite biomaterials. Moreover, in regenerative medicine, acrylic porous supports (scaffolds) need to be structured with the necessary degree, type and morphology of pores by advanced technological fabrication techniques.
- acrylic-based materials
- tissue engineering
Acrylic-based materials have been used in medicine and dentistry over decades. Specific examples in current clinical use are corneal prosthesis, intraocular lenses and contact lenses in ophthalmology  and bone cements for orthopaedic applications , tissue engineering  and dental restoratives  because of their versatile properties . A significant number of these acrylic polymers have been affirmed by the US Food and Drug Administration (FDA) for different applications. Nonetheless, a considerable number of potential clinical applications are impeded by their inadequate mechanical properties, biological behaviour, electrical and/or thermal capacity, interaction with body fluids, antimicrobial response and porosity in porous platforms (scaffolds) for tissue engineering applications. To address some of these limitations of existing acrylates, new acrylic-based materials with superior properties have been produced and are currently under being researched to resolve these problems by means of diverse fabrication strategies such as multicomponent polymeric systems or by incorporation of other materials and/or nanomaterials such as graphene to create composites or nanocomposites with a wide range of properties and also develop extensive interconnected porous structures. Biomaterials are used to engineer functional restoration of different tissues towards the repair or restoration of damaged tissues via interacting with living systems and enabling normal function. Hence the design and development of novel biomaterials involve considering physical, mechanical and biological properties of the native tissue that is being replaced with a goal of mimicking it as closely as possible to enable repair or replace and function. One of the important aspects is designing the material with desired mechanical properties that enables survival in a complex biological milieu. Recent technological advances have seen the development of complex biomaterials, and newer manufacturing techniques allow for increased spatial control over material properties. Despite the current advances, the improvement of mechanical properties of acrylics still remains a challenge and needs further investigation [6, 7, 8, 9, 10, 11].
2. Mechanical performance
The enhancement of the mechanical performance of acrylics is one of the hot themes in the area of biomedical engineering, and numerous researchers have been working on this field for many years. Acrylics can be reinforced through different methods and techniques: by incorporating ceramic additives to form composites ; microphase-separated morphologies such as block copolymers, in which hydrophobic and hydrophilic domains alternate ; increasing the cross-linking density ; binary systems composed of two or more mixed polymers as interpenetrating polymer networks [15, 16]; reinforced acrylic-based composites with embedded fibres ; plasma-induced polymerisation of an acrylic hydrogel onto a hydrophobic acrylic support [7, 18]; and nanosilica reinforcement obtained through sol-gel reactions . Nevertheless, new procedures to enhance the mechanical behaviour of acrylics have been performed by incorporating advanced materials such as graphene (2010 Nobel Prize in Physics)  and other outstanding carbon-based materials such as carbon nanotubes (CNT) . Graphene derivatives such as graphene oxide (GO) [22, 23, 24] or reduced GO (rGO)  have also exhibited excellent reinforcement for acrylics, especially hydrated acrylic hydrogels, and enhancement of many other properties.
2.1 Interpenetrating polymer networks
Interpenetrating polymer networks (IPN) as reinforced polymer networks containing acrylic polymers have gained much attention in the biomedical field during the last few decades. An IPN consists of two separate but interwoven polymer networks, which can enhance and/or combine functional properties. In this advanced multicomponent polymeric system, there are not any covalent bonds between them, but at least one of them is cross-linked within the immediate presence of the other. In this field, there are six basic multicomponent polymeric structures: mechanical blends, block copolymers, graft copolymers, AB-cross-linked copolymer, semi-IPNs and full IPNs . A full IPN results is produced if a cross-linker is present in the polymeric system . However, a semi- or pseudo-IPN polymer network possessing linear polymers embedded within the first cross-linked network is formed in the absence of cross-linking [28, 29]. Simultaneous interpenetrating polymer networks (SINs) are produced when the precursors of both networks are mixed and the two networks are formed at the same time or in the form of sequential IPNs, by swelling of a single-polymer network into a solution containing the mixture of monomer, initiator, activator and cross-linker. Thus, for example, urethane acrylate resin networks have been reinforced with epoxy networks in the form of SINs . Full IPNs and semi-IPNs have been prepared with epoxy resin and poly(ethyl methacrylate) (PEMA) utilising the sequential mode of synthesis . Both types of networks showed a gradual decrease of modulus and tensile strength performance and an increase of elongation at break and toughness with increasing PEMA content. Simultaneous semi-interpenetrating polymer networks (semi-SINs) of epoxy resin-acrylate polyurethane with high compatibility have been synthesised by simultaneous photopolymerisation . More recently oxirane-acrylate IPN’s were reported to enhance the hydrophobic nature of dental composites and lower degradation and shrinkage stress than commonly used bis-GMA resins; however, the mechanical properties were not adequate . Pseudo-SIPNs have been prepared by melt blending of poly(methyl methacrylate) (PMMA) and double-C60-end-capped poly(ethylene oxide) (FPEOF) that exhibited a storage modulus 16 times higher than PMMA, which are as similar to nanocomposites of PMMA with carbon nanotubes .
Acrylic-based IPN hydrogels are also produced with the goal of improving the mechanical performance and swelling-deswelling action of acrylic hydrogels . In this way, for instance, hydrophilic interpenetrating polymer networks (IPN) with good mechanical properties even in the hydrated state were produced with chitosan and poly(acrylic acid) (PAA) .
2.2 Composite biomaterials
Most chemical modifications of acrylic hydrogels do not result in a significant change of the overall mechanical properties since the main structural skeletons of these polymers or copolymers remain weak. On the contrary, the reinforcement achieved by the incorporation of fibre into acrylic polymer matrices is different because the added fibres impart high strength to the networks with the main skeleton of the composites. Materials reinforced with fibre are composite materials consisting of a polymer phase embedded with high-strength fibres, such as glass, aramid and carbon . In this type of materials, the mechanical performance is significantly enhanced, and the biocompatible properties of the acrylic polymer phase should remain unmodified. Thus, acrylic resin polymers have been reinforced with glass fibres for dental applications , and acrylic hydrogels such as poly(2-hydroxyethyl methacrylate), which is one of the most popular biomaterials, have been used to manufacture fibre-reinforced composites by inclusion of various kinds of woven and knitted fabrics and fibres, in order to improve overall qualities of the PHEMA-based artificial skin for wound dressing applications . Nevertheless, in the last recent decades, natural fibres have attracted much attention as reinforcement agents for polymer-based composites due to their advantages over other types of conventional fibres made with glass or carbon . Thus, natural fibres, such as flax, hemp, sisal, jute, kenaf, coir, kapok and banana, among many others, have shown many advantages over man-made glass and carbon fibres: lower cost, lower density, comparable specific tensile performance, less energy consumption, nonabrasive, not irritating, lower health risk, renewable, biodegradable and recyclable . Thus, in the field of acrylic polymers, ultra-long chitin natural fibres obtained in a sustainable way, that is, from marine-river crab shell wastes, have been incorporated into PMMA resins to produce nanocomposites with outstanding properties for biomedical and bioengineering applications .
2.3 Nanocomposite biomaterials
Nanocomposites are of particularly interest due to the fact that they exhibit both individual properties of the polymer and properties due to the presence of nanoparticles, and this additive effect has led to several therapeutic and diagnostic applications . Another reinforcing alternative for acrylic polymers consists of adding nanomaterials such as silica, carbon nanomaterials, nanofibres or other nanoparticles. Silica is biocompatible, possesses bioactive properties  and can improve the mechanical behaviour of acrylics through filling or by the sol–gel process . Thus, for example, biphasic matrices of hybrid nanocomposite materials consisting of an organic phase of poly(2-hydroxyethyl acrylate) and an inorganic phase of silica network obtained by the sol–gel process of tetraethoxysilane (TEOS) exhibited a very significant enhancement of the mechanical properties . The combination of interpenetrated polymer networks and nanosilica filling has been explored, and simultaneous polyurethane/PEMA interpenetrating polymer networks with silica filler consisting of very fine powders with an approximate diameter of 5 nm were reported to significantly improve material strength . Polymer nanocomposites have significantly influenced the field of biomedicine. In this regard, graphene-based nanocomposites have been reported to enhance the physical and biological properties of a wide range of polymers of different chemical natures [24, 45, 46, 47, 48, 49, 50, 51, 52, 53]. Graphene (GN) is a 2D monolayer of sp2-bonded carbon atoms  very promising in a wide range of industrial fields due to its outstanding electrical and thermal properties [55, 56] and high mechanical performance . In addition, it has been demonstrated that graphene, in the biomedical field, promotes adherence of human osteoblasts and mesenchymal stromal cells . Graphene has exhibit potential application in the development of new reinforced nanocomposites such as magnetite-GNs/poly(arylene-ether-nitrile) . Furthermore, GN is able to enhance the shape memory of acrylic polymers such as poly(acrylamide-co-acrylic acid), and it possesses self-healing ability when its content is between 10 and 30% . The oxidised form of GN, graphene oxide (GO), can also improve the mechanical strength and modulus of acrylic polymer networks such as poly(acrylamide) (PAM) hydrogels . GO is also a two-dimensional nanomaterial usually produced from natural graphite by exfoliation into monolayer sheets. GO possesses oxygenated functional groups at the basal plane and at the edges, hydroxyl (▬OH), epoxy (▬C▬O▬C▬), carboxyl (▬COOH) and carbonyl (▬C═O), which render its dispersion in aqueous solution easier . The outstanding unique properties of GO, such as high tensile modulus (1.0 TPa), ultimate strength (130 GPa) and electrical and thermal properties , render this carbon nanomaterial an ideal candidate for a broad range of applications in the field of new advanced materials. Thus, for instance, when GO nanosheets are introduced into weak and brittle PAM hydrogels, their mechanical properties improve significantly . The incorporation of GO nanosheets into poly (acrylic acid)/gelatin composite hydrogels increased significantly their Young’s modulus and maximum stress. In this study, the hydrogel with GO (0.2%
3. Electrical properties
The electrical properties of acrylics are important in some biomedical and bioengineering fields because various types of electrical stimulation can regulate cell physiological activities such as division , migration , differentiation and cell death . Promotion of spinal cord repair and successful cancer therapy has been also achieved by a combination of electrical stimulation and the non-invasive nature of these polymers [78, 79, 80]. For that reason, the development of new conductive acrylic-based materials for biomedical applications is gaining much attention during the last decades. Graphene, a nanocarbon material, has been recently very effective as an electrode material with very high conductivity . Although graphene exhibits high transmittance and excellent conductivity , its fabrication is still expensive. However, GO, which is more cost-effective, possesses low conductivity due to its oxygen-containing functional groups, and it must be modified to obtain reduced graphene oxide (rGO) in order to develop electrically conductive acrylic-based resins. Thus, for instance, single-step procedures can be performed starting from a homogeneous water dispersion of GO in order to effect a reduction induced by the UV radiation during the photopolymerisation of an acrylic resin . Transparent conductive films can be also fabricated by grafting of poly(acryl amide)/poly(acrylic acid) onto the GO surface followed by a reduction to rGO nanosheets by a two-step chemical reduction . Flexible and conductive double networks (DN) of rGO and poly(acrylic acid) hydrogels have also been synthesised by a two-step preparation with a reduction-induced in situ self-assembly . Nacre-inspired acrylic-based nanocomposites of rGO and PAA have also been prepared via a vacuum-assisted filtration self-assembly process. Higher strength and toughness (2 and 3.3 times higher) were achieved with these bioinspired nanocomposites in comparison with those of the pure reduced GO film due to the high amount of hydrogen bonds between the GO nanosheets and PAA polymer chains. Furthermore, this nanocomposite also displayed high electrical conductivity (108.9 S·cm−1), which renders it a promising biomaterial for many advanced applications in biomedicine and bioengineering, such as flexible electrodes and artificial muscles. The one-dimensional carbon nanomaterials discovered by Iijima , named as carbon nanotubes (CNTs), have caused increasing interest due to their excellent electrical conductivity and remarkable mechanical properties with numerous potential nanotechnological applications . Ultrasensitive electrochemical biosensors can be developed with CNTs due to their unique electrical properties. Thus, glucose biosensor for diabetics has been developed with nanofibrous membranes of poly(acrylonitrile-co-acrylic acid) (PANCAA) filled with multiwalled carbon nanotubes (MWCNT) . Other acrylic polymers such as poly(methyl methacrylate) have been developed as nanocomposites containing various multiwalled carbon nanotube (MWCNT) contents by melt mixing to achieve high conductivity levels .
4. Thermal properties
The enhancement of the thermal properties of acrylics can increase its long-term operation at the human body temperature. Thus, for instance, semi-IPNs based on polyurethane and poly(acrylamide) exhibited enhanced thermal properties due to higher cross-link density produced by the hard segment content . Differential scanning calorimetry PHEMA/SiO2 hybrids are complicated showing complex results with two glass transition temperatures (
5. Water sorption and diffusion
Water sorption and diffusion are also very important in biomedicine because these properties play a very important role in cell survival, dimensional changes and release of small molecules which are all factors that need to be considered especially in tissue engineering applications . Thus, acrylic hydrogels such as poly(2-hydroxyethyl methacrylate) or poly(2-hydroxyethyl acrylate) are important due to their hydrophilicity, swelling and deswelling capacity [95, 96, 97]. Their outstanding water sorption properties have made this kind of hydrophilic materials very promising for a broad range of biomedical and bioengineering applications such as wound healing, controlled drug delivery, tissue engineering, etc. [5, 98]. The hydrophilic functional groups attached to the polymeric backbone of these polymers provide the ability to absorb water, whilst their resistance to dissolution arises from cross-linking of polymer chains . Nevertheless, these single-network hydrogels possess very weak mechanical performance and slow swelling response. Therefore, reinforcement strategies, such as the combination of hydrophilic and hydrophobic functional groups as multicomponent polymeric systems, are usually required for these types of polymer, which can also decrease their water sorption. The reinforcement of acrylics through the incorporation of GO nanosheets can also modify their water sorption behaviour. Thus, for example, the swelling rates of GO/poly(acrylic acid-co-acrylamide) nanocomposite hydrogels increased with increasing GO content to about 0.30%
6. Antimicrobial capacity
Microbial infections are of serious concern and often lead to implant failure, which may cause major economic losses and suffering among patients despite the use of antibiotics and the aseptic processing conditions. Therefore, novel antimicrobial materials and strategies are urgently needed in biomedicine and bioengineering . Nevertheless, acrylics itself do not possess antimicrobial activity intrinsically, and therefore some fillers and antimicrobial agents need to be incorporated usually by physical blending in order to produce an acrylic-based material able to treat and/or impede microbial infections . Thus, graphene has emerged as a novel green broad-spectrum antimicrobial material with tolerable cytotoxicity in mammalian cells. Its antimicrobial action has been reported to be produced via physical damages through direct contact of its sharp edges with microbial membranes and destructive extraction of lipid molecules. Thus, graphene-based nanocomposites can be used in a broad range of biomedical applications due to its superior antimicrobial properties and good biocompatibility . Methyl methacrylate was firstly used in tooth restoration in 1937, thereby indicating methacrylate monomers on polymerisation were biocompatible and have been extensively used as dental materials such as denture bases, adhesives, tissue conditioners, etc. . The most popular methacrylate monomers employed in commercial dental resin-based materials are methyl methacrylate (MMA), 2,2-bis[4-(2-hydroxy-3-methacryloyloxypropyl)-phenyl]propane (Bis-GMA), 1,6-bis-[2-methacryloyloxyethoxycarbonylamino]-2,4,4-trimethylhexane (UDMA) and tri-ethylene glycol dimethacrylate (TEGDMA) . Nevertheless, these polymers are not inherently antimicrobial in nature; thus, the strategy of designing acrylic hydrogels with desired antimicrobial performance is important. Silver nanoparticles (Ag NPs) exhibit strong antibacterial activity against
7. Acrylic-based scaffolds for tissue engineering
In regenerative medicine, regeneration and repair of diseased tissues can be addressed by tissue engineering approaches. A significant amount of research has focussed on the development of porous scaffolds that can interact directly with the seeded or laden cells. The porous 3D scaffolds provide the pathway for cell growth, proliferation and differentiation. The properties of the scaffolds are not only dependent on the base composition, but the structural and morphological features influence cell-material interaction. Hydrogels have emerged as leading candidates for engineered tissue scaffolds due to their biocompatibility and similarities to the native extracellular matrix. However, precise control of hydrogel properties, such as high porosity and tuning of mechanical properties, remains a challenge. Bulk porosities in polymers have been created by traditional techniques and have demonstrated success in hydrogels for tissue engineering applications. However, some problems related to direct cell encapsulation often occur. Nonetheless, a broad range of emerging technologies have demonstrated the ability to control porosity and its morphology in hydrogels, producing engineered tissues with structure and function similar to native tissues . Ideal scaffolds should mimic the natural extracellular matrix (ECM), and a balance between temporary mechanical function with mass transport to aid biological delivery and tissue regeneration is of paramount importance. The interconnection and geometry of pores depend primarily on the tissue to be regenerated which then provide information on the desired physicochemical properties and mechanical resistance of the material. Several methods and techniques have been reported to produce
Acrylic-based polymers possess versatile properties suitable for biomedical and bioengineering applications such as ophthalmology, orthopaedics, dentistry and tissue engineering. Nevertheless, the potential applications of this kind of polymers could be expanded exponentially if their chemical, physical and biological properties could be enhanced. In this regard, in the last few decades, acrylic-based materials have been produced in the form of interpenetrating polymer networks, composites with added particles such as fibres and nanocomposites with incorporated nanomaterials such as graphenes, in order to improve their mechanical, electrical, thermal, water sorption/diffusion, biological, antimicrobial and porosity properties, required for certain advanced applications. In addition, acrylic scaffolds have been fabricated with the suitable morphology for tissue regeneration by advanced fabrication methods. Nevertheless, in spite of the fabulous advancements presented in this chapter, many challenges still remain to tailor the properties of acrylate polymers for specific applications in the fields of biomedicine and bioengineering.
This work was supported by the 2019-231-003UCV grant from the Universidad Católica de Valencia