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3D Printing of hydrogel composite systems: Recent advances in technology for tissue engineering

           materials for 3D printing are hydrogels because they can   understood and evaluated conventional manufacturing
           be easily functionalized or modified, without complex   processes, hydrogel composite 3D printing systems
           synthesis steps, to replicate the physicochemical properties   remain a relatively new area of research and much more
           of most biological tissues [8,9] . They possess a highly   can be studied with regards to their physicochemical
           hydrated polymeric structure, exhibiting up to 40-fold   properties such as viscosity, dispersion, reinforcement,
           change in volume as they swell or shrink in the presence   and its size and shape [16,17] . In recent years, significant
           or absence of water, respectively, and can be modified   progress has been made in the development of 3D
           to respond to various physical and biological stimuli   printing systems for hydrogel composites with improved
           such as temperature, light, pH, ions, and biochemical   mechanical performance and biofunctionality [1,16,17] .
           signals [9,10] . These unique features make hydrogels excellent   Herein, we first provide a brief introduction of hydrogel
           environments for cell attachment and proliferation within   composite 3D printing techniques and their application
           their hydrated hydrogel networks, which offer abundant   in the field of tissue engineering. We shall categorize 3D
           space for cell growth while facilitating the transportation   printing into (a) laser based-3D printing, (b) nozzle based-
           of essential metabolites and nutrients to the encapsulated   3D printing, and (c) inkjet printer based-3D printing
           cells [8,11] . However, most hydrogels suffer from a lack of   systems, and discuss their working principles and recent
           mechanical strength and unsuitable degradation behavior   trends. In particular, we will discuss four different hydrogel
           compared with native tissues such as ligament, tendon,   composite systems: i) polymer- or hydrogel-hydrogel
           muscle, or cartilage. Therefore, augmenting the mechanical   composite, ii) particle-reinforced hydrogel composite iii)
           properties and bioactivity of hydrogel have been a   fiber-reinforced hydrogel composite, and iv) anisotropic
                                         [8]
           challenging task for material scientists .          filler-reinforced hydrogel composite, and highlight tailored
            Hydrogel composite system is one of the most suitable   physical properties and their functionality. Additionally,
           strategy for incorporating and combining various hydrogel   several emerging potential applications of hydrogel
           functions and properties, not attainable by any single   composites in the field of tissue engineering and their
                       [11]
           hydrogel alone . Over the past few decades, a diverse   accompanying challenges are discussed in parallel.
           range of reinforcements have been proposed utilizing   2. 3D Printing Technology for Hydrogels
           various composite designs such as particle-, anisotropic   Composite
           filler-, and fiber-hydrogel composite systems in which
           reinforcements are stabilized and immobilized via physical   2.1 Laser-based Hydrogel 3D Printing Systems
           or chemical interactions in the hydrogel matrix [8,9,11,12] .
           In the case of hydrogel-hydrogel composite system, the   Most laser-based 3D printing systems are applicable for
           interpenetration between the two polymer networks forms   the hydrogel composite fabrications, which builds a 3D
           a mechanical anchoring behavior, and these complexes   structures in a vat of photocurable hydrogels under the
           strongly affect the hydrogel rheology, degradation rate,   deposition of laser energy, usually UV range, in specific
                                                                             [3]
                                            [13]
           permeability, and mechanical properties . Conventional   designed patterns . The exposure of UV laser on to the
           inorganic reinforcements are based on physical interactions   surface of photocurable liquid causes gel-formation of a
           with the hydrogel matrix in which secondary or van der   thin single layer, and it is sequentially moved upward or
           Waals forces including London dispersion forces, dipolar   downward with the sample stage to allow the next layer
                                                   [14]
           interactions and hydrogen bonding are involved . These   formation on top of preformed structure. During this
           physical interactions generate strong adhesion between the   process, designed 3D structures are directly materialized
           reinforcements and hydrogel matrix, and the enhancement   in the liquid vat that means the hydrogel composites
           of hydrogel properties are dependent on the amount   can be built within the photocurable organic-inorganic
                                                                     [3,18,19]
           of reinforcements and the volume ratio of physically   solution  .
           interacted- and non-interacted-polymer networks [15] . In   Since the development of laser-based 3D printing in
           the case of chemical modifications, the introduction of   1980s, several other commercially available techniques
           chemical groups and the covalent bonding formations at   have emerged, and they are widely used for biomedical
           the interface induce superior interfacial bonding strength   applications such as scaffolds, drug delivery, implants,
                                                                         [2,18]
           of which energy is generally in between the 40 to 400 kJ/  and devices  . Laser-based 3D printing system can be
           mol i.e. much higher than physical interaction (8–16 kJ/  divided into several categories based on the type of laser
              [14]
           mol) . Thus, it is possible to provide substantial increase of   source, beam delivering system, method of scanning or
           mechanical strength to the hydrogel composite system.  exposure, and type of stage movement system. However,
            While the hydrogel composite has attracted a lot of   most of these techniques require post-processing such
           attention due to its superior properties, most review   as support removal and other unwanted materials.
           articles report on conventional fabrication techniques   In addition, a post-curing procedure is necessary to
           such as molding or casting [5,7] . Compared with well-  completely cure the built structure for intact mechanical


           2                           International Journal of Bioprinting (2018)–Volume 4, Issue 1
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