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International Journal of Bioprinting                            3D printing of PCL-ceramic composite scaffolds


            defect, trauma, or aging. TE aims to create functional   The  fundamental  concepts  that  lead  to the
            organs from patients’ cells. The process of TE starts with   establishment of bone tissue-engineered scaffolds are
            biomaterials, followed by the fabrication of scaffolds,   typically based on the selected biomaterial and production
            combining them with cells and biochemical signals, such   technique. Generally, for bone TE, pore sizes between
            as growth factors, cytokines, mechanical stimulants,   100 and 350 micrometers and porosities more than 90%
            to generate new tissue structures [1,2] . Microfabrication   are preferred. PCL is a biodegradable polymer like other
            techniques used in TE include photolithography, rapid   degradable  hydroxy polyesters such as PGA, poly-l-
            prototyping (stereolithography, extrusion deposition   lactic acid (PLLA), and their copolymers. PCL is one
            printing), and soft lithography (microcontact printing,   of the widely studied synthetic polymers in different
            micro-molding, and microfluidics) . “A biomaterial is a   formulations for TE due to its elastomeric mechanical
                                        [2]
            substance that has been engineered to take a form which,   properties and biological properties. PCL is a rigid,
            alone or as part of a complex system, is used to direct, by   flexible polymer with a semi-crystalline structure having
            control of interactions with components of living systems,   high thermal stability, low glass transition (−60°C), and
            the course of any therapeutic or diagnostic procedure, in   melting temperatures (56–65°C). The slower degradation
            human or veterinary medicine” [3-6] . Biomaterials are derived   rate and  mechanical  properties  limit the use of PCL
            from several sources such as natural materials, synthetic   compared to other polyester family members. However,
            polymers, metals, ceramics, and composites [7,8] . Naturally   the degradation kinetics and mechanical strength of the
            derived biomaterials include protein-based biomaterials   PCL can be tailored by copolymerization or blending with
            (silk fibroin, keratin, collagen, gelatin, fibrin, and eggshell   other polyesters or ceramic materials. PCL can be used
            membrane) and polysaccharide-based biomaterials    for scaffold fabrication for bone, liver, cartilage, skin, and
            (chondroitin, glucose, cellulose, alginate, hyaluronan,   protein delivery vehicles [24-28] .
            and chitin and its derivative chitosan), and decellularized   Numerous studies have been done on the blending of
            tissue biomaterials. Synthetic polymers for tissue   PCL with several bioceramics (e.g., calcium phosphate,
            regeneration include polylactic acid (PLA), polyglycolic   magnesium phosphate, biphasic calcium phosphate,
            acid (PGA), poly (lactic-co-glycolic acid) (PLGA), and   hydroxyapatite,  and  bioactive  glass),  natural  polymers
            polyurethanes. Metals include titanium alloys, nitinol,   (chitosan, elastin, collagen, gelatin, and silk), and synthetic
            magnesium alloys, stainless steel, and cobalt-chromium   polymers (PLGA, PGA, PLLA, and carbon nanotubes) to
            alloys. Composites include metal-ceramic, metal-polymer,   enhance the mechanical endurance and biocompatibility
            and polymer-ceramic [9-11] . Each of the above-mentioned   of the scaffolds . Magnesium phosphate/PCL (MP/PCL)
                                                                           [29]
            individual biomaterial groups has specific advantages and   composite  scaffold  enhances  the  polymer’s  degradation
            disadvantages. Biomaterials have played a crucial role   rate by improving the PCL hydrophilicity [30,31] . Moreover,
            in supporting and fostering regenerative cell growth in   the surface wettability of the MP/PCL can be tailored by
            the tissue engineering design paradigm and biomedical   adjusting the amount of MP particles incorporated .
                                                                                                           [32]
            devices for numerous clinical regenerative therapies [12-18] .  Blending nano-hydroxyapatite (nHA) with PCL improves
              Scaffolds are temporary structures that mimic physical   composite polymer scaffold strength (mechanical
                                                                                   [33]
            microstructures of a natural extracellular matrix (ECM)   property) and bioactivity . Biocomposite scaffolds made
            to provide desired cellular interactions and guide cells to   from polycaprolactone (PCL) and forsterite bioceramics
            grow, synthesize, and other biological molecules to form   can enhance and modulate mechanical and physical
            new functional tissues . To engineer functional tissues and   properties [34,35] . Incorporating aluminum oxide whiskers
                             [2]
            organs successfully, scaffolds should possess the minimum   within PCL significantly improves the composite scaffold’s
            requirements, such as high porosity, proper  degradation   mechanical and hydrophilic surface properties with
                                                                                                           [36]
            rate, biocompatible, high surface area, mechanical   good biocompatibility for TE and dental applications .
            integrity, enhanced cell adhesion, growth, differentiated   Composite scaffolds prepared with calcium alginate
            function, and migration . Cell proliferation, attachment,   threads and PCL demonstrate ideal porosity grade with
                               [19]
            and differentiation are affected strongly by the scaffold   suitable microstructure for enhanced bone cell growth
                                                                               [25]
            microenvironment, including the size, density of the pores,   and  differentiation .  The  presence  of  β-tricalcium
            geometry, surface properties, and windows connecting   phosphate (TCP) in PCL improves the cell proliferation
            the pores . Techniques include porogen leaching,   and compressive mechanical properties of the composite
                    [20]
                                                                                       [31,37-41]
            phase  separation,  uniaxial  freezing,  micro-molding,  gas   scaffold for bone regeneration  .
            foaming, fiber meshes/fiber bonding, electrospinning, and   Magnesium phosphate and calcium phosphate-based
            additive manufacturing (laser-based, nozzle-based, and   bioceramics are well-known in the biomaterials field and
            printer-based) are used for the fabrication of scaffolds [21-23] .  have been used separately with PCL scaffolds. However,


            Volume 9 Issue 6 (2023)                        540                         https://doi.org/10.36922/ijb.0196
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