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International Journal of Bioprinting                             3D-printed PCL-MNP multifunctional scaffolds




            incorporating growth factors, which enhance cell viability   Other  than  their  use  in  non-invasive  cancer
            but come at the cost of limited shelf-life.  In addition to   management, they are increasingly being employed for
                                             2,3
            tissue regeneration, these scaffolds also serve as delivery   enhancing bone tissue regrowth. There is evidence to
            platforms for drugs and other therapeutic agents to treat   suggest that a magnetic field stimulus aids the bone tissue
                                                      4
            diseases such as cancer via hypothermia treatment.  The   regeneration process as a result of its osteoinductive
            3D microenvironment provided by these scaffolds seeks   properties. 18,19  This works by using the magnetic field to
            to mimic the native tissue microenvironment, which   activate specific cell receptors and corresponding signaling
            subsequently facilitates  cell  proliferation  and tissue  in-  pathways, which increases overall cell activity and serves
            growth and is ideal for localized delivery of drugs at the   as a modulator for tissue  regeneration in the body. 20–23
            target site.                                       Magnetic field stimulation for tissue engineering can be
                    5
                                                               utilized for both soft and hard tissues, including cartilage,
               One particular class of bioactive agents that has   muscle tissues, and bone tissues.  Paun et al.  observed
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            caught the attention of researchers and is increasingly   that upon the application of a static magnetic field,
            being investigated is magnetic nanoparticles (MNPs).   mesenchymal stem cells (MSCs) proliferated and were
            These particles can be placed in an alternating magnetic   influenced to differentiate into osteogenic-type cells. Jia
            field (AMF) to promote hyperthermia treatment and aid   et al.  demonstrated that mesoporous silica-coated MNPs
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            bone regeneration.  Hence, MNPs provide an excellent   (M-MSNs) enhance bone tissue regrowth in a rat model,
                           6,7
            basis for the creation of multi-functional scaffolds. While   suggesting their use for clinical purposes. They validated
            several different kinds of MNPs exist, such as iron oxide   their findings through a series of tests, including imaging,
            nanoparticles (IONPs), magnesioferrite nanoparticles,   histological, and immunohistochemical examination.
            copper  IONPs,  manganese-based nanoparticles, and   Wu et al.  found that low doses of Fe O  nanoparticles,
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                                                                                               3
                                                                                                 4
            cobalt-based nanoparticles,  the vast majority of the   in conjunction with a magnetic field, led to osteogenesis
                                  8,9
            research  deals  specifically  with  magnetic  IONPs.  This  is   enhancement induced by stem cell exosomes. Jasemi et al.
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            due to the beneficial biological properties of iron oxide,   fabricated  composite  calcium  and  zirconium  scaffolds
            such as its biocompatibility and low toxicity, in addition to   with 5–15 wt% MNPs; they observed a positive correlation
            the fact that it is the only metal-based nanoparticle cleared   with respect to the scaffold modulus and the growth of an
            for clinical use by the United States (US) Food and Drug   apatite layer on the scaffold. Zhao et al.  produced chitosan
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            Administration (FDA).  While several researchers have   and collagen composite scaffolds, incorporated with nano-
                               10
            utilized modified magnetic IONPs to achieve their goals,   hydroxyapatite  and  Fe O   nanoparticles,  and  implanted
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                                                                                 3
            the base material remains iron oxide. Diaz et al.  doped   them in vivo using a rat skull model. They found that these
                                                   11
            their MNPs with nanohydroxyapatite to enhance osteoblast   composite scaffolds displayed greater tissue compatibility
            adhesion, proliferation, and differentiation. Cojocaru   and bone regrowth compared to the control set.
            et al.  fabricated a novel magnetic scaffold by combining   Despite the growing interest in MNPs, targeting them
                12
            biopolymers, like chitosan and gelatin, with MNPs to   at the critically sized defect in the bone and/or using
            enhance cell adhesion, migration, and osteoconductivity in   them as agents of drug delivery remains a challenge.
            vivo. Li et al.  used magnetic graphene oxide in composite   Hence, 3D-printed platforms are utilized to better achieve
                      13
            polymeric scaffolds to exploit their thermal attributes for   these objectives. Zhang et  al.  fabricated an additively
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            effective tumor treatment.  Despite their advantageous   manufactured composite scaffold made from bioactive
                                  14
            biological and mechanical properties, it is their magnetic   glass,  polycaprolactone  (PCL),  and  MNPs.  The  PCL
            attributes that have attracted the attention of researchers   provided a biocompatible matrix and was also responsible
            for  use  in  drug  delivery  systems  and  non-invasive   for providing an adequate surface for cell adhesion and
            tumor management.  MNPs can possess diamagnetic,   growth.  The  3D-printed  scaffold  was  found  to  satisfy
                             15
            paramagnetic, and ferromagnetic properties depending   the dual goal of sustained drug release and exhibiting
            on their susceptibility to the application of an AMF. When   greater osteogenic activity. Dankova et  al.  used the
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            these  nanoparticles  are  placed  in  an  AMF,  it  creates  a   electrospinning technique to create PCL and MNP
            dipole moment, which is aligned in the direction of the   nanofibrous scaffolds. These composite scaffolds were
            field for paramagnetic particles and opposite to the field   biocompatible and also supported MSC proliferation and
            in the case of diamagnetic particles.  When the particle   osteogenic differentiation. De Santis et al.  3D printed a
                                         16
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            size of these nanoparticles is below 30 nm, they exhibit a   PCL and iron-doped hydroxyapatite nanoparticle scaffold
            superparamagnetic effect, which essentially allows each   and tested them  in vitro and  in vivo. While the  in vitro
            particle to possess its respective local magnetic field,   analysis reported enhanced cell growth, the in vivo rabbit
                                                  17
            driving interaction at the cell-scaffold interface.    model displayed excellent bone growth within just 4 weeks.
            Volume 10 Issue 6 (2024)                       392                                doi: 10.36922/ijb.4538
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