Abstract
Acrylic-based polymers have many currently important biomedical applications such as contact lenses, corneal prosthesis, bone cements, tissue engineering, etc. due to their excellent biocompatibility and suitable performance in mechanical properties, among many other applications. Many of these biomaterials have been approved by the US Food and Drug Administration (FDA) for various applications. However, the potential uses of these polymeric materials in the biomedical industry could be increased exponentially if some of their acrylic properties (mechanical strength, electrical and/or thermal properties, water sorption and diffusion, biological interactions, antibacterial activity, porosity, etc.) are enhanced. Thus, acrylics have been fabricated as multicomponent polymeric systems in the form of interpenetrated polymer networks or combined with other advanced materials such as fibers, nanofibers, graphene and its derivatives and/or many other kinds of nanoparticles to form composite or nanocomposite materials, which are expected to exhibit superior properties. Besides, in regenerative medicine, acrylic scaffolds need to be designed with the required extent and morphology of pores by sophisticated techniques. Even though the great advances have been achieved so far, much research has to be carried out still in order to find new strategies to improve the above-mentioned properties.
Keywords
- biomedical applications
- hydrogels
- acrylic properties
- nanocomposites
- latest improvements
1. Introduction
Acrylics are currently used in many important fields of the biomedical industry such as corneal prosthesis, intraocular lenses and contact lenses in ophthalmology [1], bone cements for orthopedic applications [2], tissue engineering [3], etc. due to their excellent properties such as biocompatibility and suitable mechanical performance, among others [4]. Many of these acrylic products for various applications have been approved by the US Food and Drug Administration (FDA) and are expected to produce massively. However, many of their potential uses required for many biomedical applications are sometimes hindered by their low mechanical strength, biological interactions, electrical and/or thermal properties, water sorption and diffusion, antibacterial activity, porosity, etc. when they are synthesized as scaffolds for tissue engineering applications. Thus, new advanced acrylic-based materials have been developed and are currently under intensive research to solve all these problems by means of multicomponent polymeric systems or by combination with other materials and/or nanomaterials to form composites or nanocomposites with or without interconnected porous morphology.
2. Mechanical properties
The improvement of the mechanical properties of acrylics is one of the
2.1. IPNs
Acrylic-based interpenetrating polymer networks (IPN) have gained greater attention during last decades, mainly due to their biomedical applications as reinforced polymer networks. The use of an IPN, which consists of two separate but interwoven polymer networks, is a chemical procedure that is often used in polymer science to control, enhance and/or combine functional properties. These are advanced multicomponent polymeric systems of crosslinked polymer networks without any covalent bonds between them, where at least one of them is synthesized and/or crosslinked within the immediate presence of the other. It is important to differentiate between the six basic multicomponent polymeric structures (Figure 1).
If a crosslinker is present in the polymeric system, fully IPN [17] result, while in the absence of crosslinking, a network having linear polymers embedded within the first crosslinked network is formed (semi- or pseudo-IPN) [18, 19]. Acrylic-based IPNs are prepared usually in the form of simultaneous interpenetrating polymer networks (SINs), in which the precursors of both networks are mixed and the two networks are synthesized 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 and activator, usually with a crosslinker. Thus, urethane acrylate resin networks were greatly reinforced by epoxy networks in SINs composed of both resins [20]. Full IPNs and semi-IPNs of the epoxy resin and poly(ethyl methacrylate) (PEMA) were also prepared by the sequential mode of synthesis, and these showed a gradual decrease of modulus and tensile strength properties with consequent increase in elongation at break and toughness for both types of IPNs with increases in PEMA content [21]. Combinations of different kinds of IPNs have been synthesized using simultaneous photopolymerization, which gave rise to simultaneous semi-interpenetrating polymer networks (semi-SINs) of epoxy resin-acrylate polyurethane semi-interpenetrating networks having very high compatibility [22].
Pseudo-SIPNs were prepared by melt blending of poly(methyl methacrylate) (PMMA), and double-C60-end-capped poly(ethylene oxide) (FPEOF) exhibited a storage modulus of 16 times larger than that of PMMA, which are as good as those of PMMA/carbon nanotube nanocomposites [19].
Acrylic-based IPN hydrogels are also developed with the aim of enhancing the mechanical strength and swelling/deswelling response of these acrylic hydrogels [23]. For example, interpenetrating polymer network (IPN) hydrogels composed of chitosan and poly(acrylic acid) (PAA) are synthesized by employing the UV irradiation method and showed that even in the swollen state, the present chitosan/PAA IPNs possessed good mechanical properties [24].
‘Smart’ hydrogels are able to significantly change their volume/shape in response to small alterations of certain parameters of the environment. These responsive hydrogels have numerous applications, most of them focussing on biological and therapeutic demands [25, 26] and sensing applications [27].
Although IPNs based on hydrogels have been extensively reported, the combination of liquid crystalline (LC) property-based hydrogels has been rarely explored. In this case, the anisotropic and molecular order of liquid crystals can be combined with the responsive isotropic properties of hydrogels. Thus, advanced stimuli-responsive materials based on interpenetrating liquid crystal-hydrogel polymer networks have been recently fabricated consisting of a cholesteric liquid crystalline network that reflects color and an interwoven poly(acrylic acid) network that provides a humidity and pH response [28].
2.2. Composites
Several kinds of chemical modifications of acrylic hydrogels do not have a significant change of the overall mechanical strength because the main structural skeletons of these polymers or copolymers are still weak. On the contrary, the method of fiber reinforcement to produce composites is different because the added fabrics impart high strength to the networks which not only just embed inside the membranes but also form the main skeleton of the composites. A fiber-reinforced polymer is a composite material consisting of a polymer matrix imbedded with high-strength fibers such as glass, aramid and carbon [29]. In such kind of materials, the mechanical properties are presumed to be improved and the biocompatible characteristics of the acrylic polymer should remain the same. Thus, acrylic resin polymers have been reinforced with glass fibers for dental applications [30], and acrylic hydrogels such as poly(2-hydroxyethyl methacrylate), which is one of the most popular biomaterials, have been manufactured by adding various kinds of weaved and knitted fabrics and fibers, in order to improve overall qualities of the poly(2-hydroxethyl methacrylate) (PHEMA)-based artificial skin for advanced wound dressing usage [31]. However, in the recent decades, natural fibers as an alternative reinforcement in polymer composites have attracted the attention of many research groups due to their advantages over conventional glass and carbon fibers [32]. These natural fibers include flax, hemp, jute, sisal, kenaf, coir, kapok, banana, henequen and many others, which offer various advantages over man-made glass and carbon fibers such as low-cost, low-density, comparable specific tensile properties, non-abrasive to the equipment, non-irritation to the skin, reduced energy consumption, less health risk, renewability, recyclability and bio-degradability [33]. Thus, ultra-long chitin natural fibers were incorporated into PMMA resin to prepare PMMA/chitin nanocomposites with improved properties [34]. This achievement is a significantly environmental move toward the sustainable utilization of marine-river crab shell wastes for biomedical applications.
2.3. Nanocomposites
Another alternative and very promising way of reinforcing acrylic polymers consists of the incorporation of nanomaterials such as silica, graphene and its derivatives, nanofibers or many other nanoparticles. Silica is a biocompatible material and has been reported to possess bioactive properties [35]. Silica can improve the mechanical properties of acrylics through nanosilica filling or the well-known sol-gel process, which offers a new approach to the synthesis of nanocomposite materials with domain sizes approaching the molecular level [36]. Thus, a biphasic matrix of a hybrid (inorganic-organic) nanocomposite materials of poly(2-hydroxyethyl acrylate) with a silica network obtained by an acid-catalyzed sol-gel process of tetraethoxysilane (TEOS) showed a very significant improvement of the mechanical properties of the pure hydrogel [37].
The combination of the reinforcement through interpenetrated polymer networks and nanosilica filling is another strategy that has also been used in the past. For example, simultaneous polyurethane/poly(ethyl methacrylate) interpenetrating polymer network with silica filler consisting of very fine powders with an approximate diameter of 5 nm also showed an important improvement of material strength [38].
Graphene (GN) is a two-dimensional (2D) monolayer of sp2-bonded carbon atoms, which has attracted increasing attention [39] owing to its excellent electrical and thermal conductivities [40, 41] and great mechanical strength [42]. Besides, graphene promotes adherence of human osteoblasts and mesenchymal stromal cells [43], which render this nanomaterial also very promising material in the biomedical field. Thus, it has shown potential applications in nanocomposites such as magnetite-GNs/poly(arylene-ether-nitrile) nanocomposites because their mechanical properties were significantly enhanced by the incorporation of magnetite-GNs hybrids [44]. Besides, GN enhances the shape memory of poly(acrylamide-co-acrylic acid) and self-healing ability when the content of graphene is in the range of 10–30%, even though this copolymer itself has poor shape memory ability [45]. There are some reports that graphene oxide (GO) nanosheets can also enhance the mechanical strength of polymer substrates such as poly(acrylamide) (PAM) hydrogels [46]. GO is also a 2D nanomaterial prepared from natural graphite that can be easily exfoliated into monolayer sheets. GO has many hydrophilic oxygenated functional groups, including hydroxyl (-OH), epoxy (-C-O-C-), carbonyl (-C=O) and carboxyl (-COOH), which enable its dispersion in water solution [47]. The diversity of unique properties of GO, including great tensile modulus (1.0 TPa), ultimate strength (130 GPa) and electrical and thermal properties [48], renders graphene oxide an ideal carbon nanomaterial for variety of applications toward the development of new advanced materials. Thus, GO added into PAM hydrogels improved very much the mechanical performance of the original PAM hydrogels, which generally exhibit pronounced weakness and brittleness [46]. In the same way, the addition of GO nanosheets increased the Young’s modulus and maximum stress of poly (acrylic acid)/gelatin composite hydrogels significantly as compared with control (0.0 wt.% GO). The highest Young’s modulus was observed for hydrogel with GO (0.2 wt.%)/PAA (20 wt.%), whereas the highest maximum stress was detected for GO (0.2 wt.%)/PAA (40 wt.%) specimen. These results suggested that the application of GO nanosheets could be used to improve mechanical properties of hydrogel materials, which is very beneficial for tissue engineering applications [14]. The other derivatives of graphene such as chemically modified graphene (CMG) fillers have been used in nanocomposites of PMMA and were compared with the GO filling. These results showed an elastic modulus of GO/PMMA and RG-O/PMMA composites improved by 28% by just loading 1 wt.%. Fracture strength increased for GO/PMMA composites but decreased for RG-O/PMMA composites [49].
Single-wall carbon nanotubes (SWCNTs), multi-wall carbon nanotubes (MWCNTs) as well as carbon nanofibers (CNFs) are being used for reinforcing polymer matrices such as poly(methyl methacrylate) by melt blending. Thus, for example, using an amount of carbon nanofibers of 5 wt.%, the nanocomposites improved over 50% of their axial tensile modulus as compared to the control PMMA. The PMMA/CNFs nanocomposite fibers also show enhanced thermal stability, significantly reduced shrinkage and enhanced modulus retention with temperature, as well as improved compressive strength [50]. The electrical properties and electromechanical responses of acrylic materials such as acrylic elastomers and styrene copolymers can be improved toward electroactive applications such as artificial muscle and/or micro-electro-mechanical systems (MEMS) devices [51].
The other novel nanocomposite hydrogels such as those prepared with polyacrylamide (PAM) as a matrix material reinforced with natural chitosan nanofibers via
Reinforcement can be also performed with plant fiber-based nanofibers by a successful fibrillation of wood pulp fibers into nanofiber bundles, which are thin enough to work, as well as bacterial cellulose in maintaining the transparency of resin [53].
The other nanoparticles such as clay have been employed to reinforce acrylic polymers. These polymer-clay nanocomposites such as PMMA/clay constitute a class of materials in which the polymer matrix is reinforced by uniformly dispersed inorganic particles (usually 10 wt.% or less) having at least one dimension in the nanometre scale and exhibiting enhanced mechanical and thermal properties when compared to pure polymer or conventional composites [54].
3. Electrical properties
The electrical properties are very important in some biomedical fields because various types of electrical stimulation can regulate cell physiological activities such as division [55], migration [56], differentiation and cell death [57]. The electrical stimulation also has been employed in promoting healing for spinal cord repair and cancer therapy due to its non-invasiveness of these polymers [58–60]. For these reasons, much emphasis was given in developing these new acrylic-based materials in biomedical application where the conductivity of the biomaterials is essential. Recently, nanocarbon materials such as graphene had been considered to be very effective electrode material with very high conductivity. The graphene has high transmittance and excellent conductivity [40] as was mentioned earlier. But, its production is still very expensive, and more studies are expected to carry out with its derivative, graphene oxide. However, in order to develop electrically conductive acrylic-based resins, GO, which has a very low conductivity due to their oxygen-containing functional groups, must be modified to obtain reduced graphene oxide (rGO). Thus, for example, following a single-step procedure starting from a homogeneous water dispersion of GO, it is possible to undergo reduction induced by the UV radiation during the photopolymerization of an acrylic resin [61]. The transparent conductive films were also produced by grafting poly(acryl amide)/poly(acrylic acid) on the GO surface followed by a reduction to rGO nanosheets by a two-step chemical reduction with increased conductivity [62]. The inorganic-organic double network (DN) flexible and conductive hydrogel of rGO and poly(acrylic acid) has also been prepared by a two-step synthesis with a reduction-induced
Carbon nanotubes (CNTs), discovered by Iijima [65], have also been attracting intensive attention because of their excellent electrical properties with a superb conductivity, remarkable mechanical strength and modulus with many potential technological applications [66]. CNTs offer the possibility of developing ultrasensitive electrochemical biosensors due to unique electrical properties. Thus, nanofibrous membranes filled with multi-walled carbon nanotubes (MWCNT) were electrospun from the mixture of poly(acrylonitrile-co-acrylic acid) (PANCAA) and MWCNT to develop a glucose biosensor for diabetics [67].
The other nanocomposites of poly(methyl methacrylate) containing various multi-walled carbon nanotube (MWCNT) contents have been prepared using melt mixing to achieve high conductivity levels in the nanocomposites [68].
4. Thermal properties
Even though biomaterials do not need to endure temperatures higher than that of the human body, the improvement of thermal properties can increase its long-term operation. Thus, for example, the incorporation of polyurethane into polyacrylamide network in the form of an interpenetrating polymer networks enhanced the thermal properties of these semi-IPNs due to higher crosslink density imparted by the hard segment content [18]. Though silica can improve the mechanical properties of acrylic polymers, the differential scanning calorimetry results of PHEMA/SiO2 hybrids are complicated, showing two glass transition temperatures, and it was shown that the SiO2 content is an important factor in influencing the shift of the Tg transition [69]. However, polymer nanocomposites with functionalized graphene sheets (FGNS) showed an unprecedented shift in glass transition temperature of up to 40 and 30°C in poly(acrylonitrile) with 1 wt.% of FGNS and in poly(methyl methacrylate) with only 0.05 wt.%, respectively [70]. Besides, the thermal stability of magnetite-graphene/poly(arylene-ether-nitrile) nanocomposites were significantly enhanced by the incorporation of magnetite-graphene hybrids [44]. The nanocomposites of PMMA with chemically modified graphene (CMG) and GO fillers made by
Another strategy to improve the thermal properties of acrylic polymers is by nanoparticle filling. Thus, the thermal performance of well-known acrylic polymers such as PMMA can be significantly improved by filling of nanometric particles (5, 10 15 and 20%) of titanium oxide (TiO2) and ferric oxide (Fe2O3) by the solvent casting method [71, 72].
Thermal degradation can also be improved in acrylic-based materials by nanoparticle filling. For example, the experimental results obtained by thermogravimetric analysis (TGA) of PMMA with TiO2 and Fe2O3 showed that these nanoparticles can improve the thermal stability of PMMA by about 50°C by loading 5 wt.% of fillers [72]. The TGA also showed that the presence of small amounts of Pd nanoparticles (0.0005–0.005 vol%) in PMMA/Pd nanocomposites significantly improved the thermal stability of PMMA, as shown by a degradation initiation retarded by 75°C and a gain of 32°C at the maximum decomposition rate [73].
Acrylic hydrogels are hydrophilic polymers and are able to absorb large amounts of water in their biomedical applications due to contact with cells or tissue in the human body. Therefore, the thermal analysis of water and its influence on the swollen hydrogel properties becomes essential. Thus, many studies have been done in this way with acrylic hydrogels such as PHEMA [74], bulk and plasma-polymerized poly(2-hydroxyethyl acrylate) (PHEA) [75], Poly(ethyl acrylate) [76], etc.
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, especially in tissue engineering applications [3]. Thus, acrylic hydrogels such as poly(2-hydroxyethyl methacrylate) or poly(2-hydroxyethyl acrylate), are very important hydrophilic materials as these polymers were able to absorb and swell retaining large amounts of water within their structure[77–80]. The excellent water sorption property has made these types of materials very promising in a wide range of biomedical applications such as controlled drug delivery, tissue engineering, wound healing, etc. [4, 81]. The ability of hydrogels to absorb water arises from hydrophilic functional groups attached to the polymeric backbone, while their resistance to dissolution arises from crosslinks between network chains [82]. However, these single-network hydrogels have weak mechanical properties and slow response at swelling. Therefore, they are in need of reinforcement, as already mentioned, which can also modify their water sorption properties. For example, the combination of hydrophilic and hydrophobic functional groups of acrylic polymers as multicomponent polymeric systems is shown in Figure 1.
The reinforcement of acrylics through GO loading can modify the water sorption behavior of the polymers. Thus, the swelling rates of graphene oxide/poly(acrylic acid-co-acrylamide) nanocomposite hydrogels increased with increase in the GO loadings to 0.30 wt.% and then decreased with further increasing GO loadings. It is worth noting that the hydrogel with only 0.10 wt.% GO exhibited significant improvement of swelling capacity in neutral medium and could also retain relatively higher swelling rates to a certain degree in acidic and basic solutions. Therefore, these GO-based superabsorbent acrylic hydrogels have very potential applications in many fields such as biomedical engineering and hygienic products [47].
The mechanism of water diffusion [83] can also be altered by the reinforcement of acrylics through any of the methods shown in Section 1. Thus, poly(acrylic acid)-GO nanocomposite hydrogels shows non-Fickian anomalous diffusion and the deswelling ratio decreases with increasing GO content [48].
A new method (ultrasound synthesis) has been developed to prepare superabsorbent polymers of sodium lignosulfonate-grafted poly(acrylic acid-co-acryl amide). This superabsorbent acrylic-based polymer exhibited also a non-Fickian water diffusion transport and a maximum water absorbency of 1350 g⋅g−1 [84].
There are many acrylic hydrogels, which exhibit a non-Fickian diffusion behavior such as poly(2-hydroxyethyl acrylate) [79, 80]. Even though water sorption is not classically Fickian, it has been observed in a variety of polymers such as PHEMA, that an important water-swellable biomedical polymer is controlled by Fickian diffusion [85]. Thus, copolymeric hydrogels based on 2-hydroxyethyl methacrylate (HEMA) and epoxy methacrylate (EMA) synthesized by bulk polymerizations showed that the swelling process of these polymers also follows Fickian behavior and the equilibrium water content (EWC) decreased with increase in EMA content due to its hydrophobicity [86].
It is remarkable that the pH has a big influence in the swelling properties and diffusion mechanism of acrylic-based materials. Thus, the swelling properties of semi-interpenetrating polymer networks of acrylamide-based polyurethanes decreased in acidic pH, while a reverse trend was seen in basic pH. However, these semi-IPNs were found to be hydrolytically stable in phosphate buffer solution, which makes them to be a potential material for biomedical applications [18].
Polyacrylic acid is a pH-sensitive and biocompatible polymer that is being used in many biomedical fields [26]. It has attracted considerable interest because of its therapeutic use, due to its ability to swell reversibly with changes in pH. Thus, GO functionalized with PAA (GO-PAA) by
The effect of temperature on swelling properties of acrylic hydrogels is also very important [86], and they can be modified to exhibit fast temperature sensitivity, and improved oscillating swelling-deswelling properties as, for example, in thermosensitive poly(N-isopropyl acrylamide-co-acrylic acid) hydrogels [89].
6. Antibacterial activity
In biomedicine, bacterial infections can lead to implant failure, which may cause major economic losses and suffering among patients despite the use of preoperative antibiotic prophylaxis and the aseptic processing of materials. Therefore, novel antibacterial materials are urgently needed for medical uses [90]. However, acrylics itself do not have antibacterial activity intrinsically, and therefore some fillers and antibacterial agents need to be incorporated by physical blending in order to produce an acrylic-based antibacterial material [91]. Thus, graphene has emerged as a novel green broad-spectrum antibacterial material, with little bacterial resistance and tolerable cytotoxic effect on mammalian cells. It exerts its antibacterial action via physical damages through direct contact of its sharp edges with bacterial membranes and destructive extraction of lipid molecules. The graphene-based nanocomposites have a wide range of biomedical applications such as wound dressing due to its superior antibacterial properties and good biocompatibility [92].
In the field of dental materials, since methyl methacrylate was firstly used in tooth restoration in 1937, methacrylate monomers having good biocompatibility and adhesive property have been extensively used as dental materials [91]. The most commonly used methacrylate monomers 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) [93]. However, the dental materials produced with these monomers are not of antibacterial nature, which is very important in this biomedical field. Thus, another strategy to design acrylic hydrogels with desired antibacterial performance consists of adding silver nanoparticles (Ag NPs). This modification produced a strong antibacterial activity against
Infections are also frequent and highly undesired occurrences after orthopedic procedures. Besides, the growing concern caused by the rise in antibiotic resistance progressively decreased the efficacy of such drugs. Thus, in this area, the integration of silver nanoparticles in the polymeric mineralized acrylic-based nanocomposites also provides antibacterial activity against bacteria [96].
The combination of both previous strategies (graphene and Ag NPs) to design antibacterial hydrogels with good water-maintaining ability is of particular significance to promote the development of wound dressing. Thus, a series of hydrogels were synthesized by crosslinking of Ag/graphene composites with acrylic acid and N,N′-methylene bisacrylamide at different mass ratios. In this study, prepared hydrogel with an optimal Ag to graphene mass ratio of 5:1 exhibited much stronger antibacterial abilities than other hydrogels and showed excellent biocompatibility, high swelling ratio and good extensibility at the same time. Besides,
7. Porosity in scaffolds for tissue engineering
Tissue engineering holds great promise for regeneration and repair of diseased tissues, making the development of new porous supports as scaffolds for tissue regeneration a topic of great interest in biomedical research. Hydrogels have emerged as leading candidates for engineered tissue scaffolds due to of their biocompatibility and similarities to native extracellular matrix. However, precise control of hydrogel properties such as high porosity, remains a challenge. Traditional techniques for creating bulk porosity in polymers have demonstrated success in hydrogels for tissue engineering. However, some problems related to direct cell encapsulation often occur. Emerging technologies have demonstrated the ability to control porosity and morphology in hydrogels, creating engineered tissues with structure and function similar to native tissues [99].
The applications of porous materials are nowadays widespread. The interconnection and geometry of pores, which depend on the tissue to regenerate, physicochemical properties and mechanical resistance of the material, play in these biomedical applications a major role. Thus, there are several methods to produce
Another example is the novel preparation of gelatin-PHEMA porous scaffolds by freeze-drying technique, in which morphology was assessed by SEM and μ-CT (Figure 4). Four types of novel hydrogels using different methacrylamide-modified gelatin/2-hydroxyethyl methacrylate ratios between 1/0 and 1/2 (w/w) (samples from C0 to C3) were prepared in this study, and the results indicated that the HEMA content in the initial polymerization mixtures modulates the architecture of the porous scaffolds from straightforward, top-to-bottom oriented channels for hydrogels possessing the lowest HEMA content to a complex and dense internal porosity of the channels in the case of higher HEMA loaded materials. It is important to notice that the covalently bound gelatin sequences significantly improve the biocompatibility of PHEMA-based hydrogels, which is very convenient for tissue engineering purposes.
Superporous acrylic scaffolds can also be prepared by the salt-leaching technique using NaCl or (NH4)2SO4 as a porogen [111] or with many other porogenic agents such as ammonium oxalate crystals [112].
By submitting carbon dioxide (CO2) to supercritical conditions (
Probably the most sophisticated techniques to produce scaffolds are electrospinning, 3D printing and bioprinting. Electrospinning is composed of a high-voltage DC power supply, an infusion pumps and a syringe with a needle tip usually with a diameter of 0.5 mm, and for example, biodegradable nanofibrous poly(l-lactic acid) (PLLA) scaffolds have been prepared by this process for use in tissue regeneration [115]. 3D printing promises to produce complex biomedical devices according to computer design using patient-specific anatomical data. This 3D printing technique has slowly evolved to create one-of-a-kind devices, implants, scaffolds for tissue engineering and drug delivery systems among other important applications. However, several technological limitations, related to the kind of commercially printable materials available and other technical printing aspects, must still be overcome. The common 3D printing technologies such as three-dimensional printing, fused deposition modeling, selective laser sintering, stereolithography and 3D Plotting/Direct-Write/Bioprinting, are still under deep research for the progress of each technology in tissue engineering. Bioprinting is the more advanced 3D printing technology because it consists of printing cells combined with custom 3D scaffolds for personalized regenerative medicine [109].
Mechanical resistance depends both on the material properties and on the interconnected pore structure of the scaffold. This problem is more serious in the case of porous acrylic hydrogels, which exhibit very poor mechanical properties in their swollen state [80]. Therefore, it is usually necessary to enhance the mechanical properties of these porous structures by means of the methods, shown in Chapter 2, with nanomaterials or other techniques. For example, the use of a hybrid hydrogel nanocomposite of silica/poly(2-hydroxyethyl acrylate) as scaffold material matrix greatly improves the mechanical properties, and the silica phase of the scaffold was effectively interconnected and continuous, able to withstand pyrolysis without losing the pore architecture of the scaffold [37].
Other modifications of acrylics such as those of PHEMA with cholesterol methacrylate (CHLMA) and laminin have been developed in the presence of ammonium oxalate crystals to introduce interconnected superpores in the matrix in order to design superporous scaffolds that promote cell-surface interaction [116]. PHEMA has also been modified with laminin-derived Ac-CGGASIKVAVS-OH peptide sequences to construct scaffolds that promote cell adhesion and neural differentiation. With the same goal, nanofiber scaffolds prepared by electrospinning were treated with oxygen plasma and then simultaneously
Recent studies of 3D microenvironment comprising fibronectin-coated PMMA/PC-based multicomponent polymeric systems promoted differentiation of primary human osteoblasts, which hereby renders a promising tool for tissue-specific
Polysaccharide hydrogels have become increasingly studied as matrices in soft-tissue engineering due to their known cytocompatibility. Thus, for example, crosslinkable dextran methacrylates and hyaluronan methacrylate hydrogels, which are candidates as matrices for soft-tissue reconstruction, were synthesized, showing that the
Even though the great advances have been achieved in scaffold design of acrylic-based materials, much research has to be conducted still in order to find new ways and methods capable of providing suitable advanced porous materials for tissue engineering applications.
Acknowledgments
This work was supported by the 2015-162-001UCV grant from the Universidad Católica de Valencia
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