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International Journal of Bioprinting                                     Applications of 3D printing in aging



            bone regeneration ability. CS is commonly used in bone   from the 3D-printed composite scaffolds sustained for
            tissue engineering, and the mechanical characteristics   more than 20 days, demonstrating good biocompatibility
            and biocompatibility of scaffolds can be considerably   and encouraging osteogenic differentiation while reducing
            enhanced by doping CS with ceramic and metal particles.   osteoclast activation. The repair of osteoporotic defects
            Using FDM technology, Ye et al. [109]  3D-printed chitosan   and osseointegration were greatly improved by sustained
            acetic acid solution-coated poly(3-hydroxybutyrate-co-  release of BMP-2 and OPG from the composite scaffolds.
            3-hydroxyvalerate)/calcium  sulfate  hemihydrate  (PHBV/  Cui et al. [113]  created an inorganic-organic bioactive system
            CaSH) scaffolds. Rat bone marrow stromal cells (rBMSCs)   for drug delivery. The system consisted of an electron beam
            underwent osteogenic gene expression level upregulation   melting (EBM) 3D-printed inorganic porous titanium alloy
            by the PHBV/CaSH/CS scaffold, considerably increasing   surface  and  an  organic  pozzolanic  407  thermosensitive
            their osteogenic potential. Further proof that the PHBV/  hydrogel loaded with a new antiosteoporosis drug
            CaSH/CS  scaffold  might  successfully  encourage  the   (technetium methylene diphosphate, 99Tc-MDP). It
            development of new bone came from in vivo investigations.   displayed a sustained drug release profile, improved
            Ratheesh  et al. [110]  prepared a double pore size layered   osteogenic differentiation, decreased osteoclast-associated
            scaffold using polycaprolactone (PCL) in combination   gene expression, and suppressed osteoclastogenesis. It also
            with melt electrowriting (MEW) and FDM, and the layered   demonstrated  superior  biocompatibility [113] .  Li  et al. [114]
            scaffold showed improved performance with significantly   used EBM to fabricate a 3D porous titanium prosthetic
            larger specific surface area and enhanced cell proliferation,   interface  with  biomimetic  pore  size  and  porosity,  after
            which  promote  cell  adhesion  and  in vitro  osteogenesis   which it was implanted into the distal femur of osteoporotic
            compared to the FDM control scaffold.              rabbits, and rapamycin was administered via a transdermal
                                                               drug delivery system to the implantation site. Ultrasound-
               Poor osseointegration at the interface following
            arthroplasty in patients with osteoporosis caused by limited   mediated rapamycin  administration restored cellular
                                                               activity and prevented potential osteoclast induction and
            bone regeneration ability typically results in catastrophic   adipose differentiation.
            consequences such as prosthesis displacement, loosening,
            and periprosthetic fractures. To improve osseointegration   (B) The role of 3D printing in the treatment and
            under osteoporosis, Wang  et al. [111]  3D-printed a   research of cartilage diseases
            hierarchically functionalized porous Ti6Al4V scaffold   Arthroplasty is one of the best treatments for severe OA. The
            using SLM. The macroporous structure in this innovative   current gold-standard therapy for OA is total arthroplasty,
            scaffold provided mechanical support, the microporous   in which the damaged cartilage and underlying bone
            structure boosted biocompatibility and encouraged cell   are replaced with polymer and metal prostheses. This
            attachment, and the nanostructure showed biological   treatment is now approaching maturity, but still carries
            impacts. Animal studies showed that a significant amount   the risk  of failure and postoperative complications. The
            of new bone was produced around and within the distal   advent of cartilage tissue engineering promises a new
            femur of osteoporotic rats after the biofunctionalized porous   treatment  option.  New  cartilage  tissue  engineering
            Ti6Al4V scaffold was implanted. By inhibiting the Notch1   methods, such as 3D printing of bioinks that contain cells
            signaling pathway and increasing the production of anti-  and bioactive materials, have the potential to produce
            inflammatory cytokines, controlled release of epimedium   prostheses with bionic structures and functions, and show
            and Mg  from biologically functionalized porous titanium   great advantages for the development of personalized
                  2+
            (PT) significantly improved the polarization of M0   cartilage implant. It is particularly important to identify
            macrophages to M2 type and significantly improved bone   bioactive materials and printing strategies that are suitable
            metabolism, which improved bone regeneration among   for cartilage tissue engineering [115] . With the use of DIW,
            PT and osteoporotic bone [111] .
                                                               You  et al. [116]  effectively 3D-printed porous cell-loaded
               The  fabrication  of  targeted  drug  delivery  and  release   hydrogel scaffolds utilizing ATDC5 chondrocyte cells
            systems for patients with osteoporosis and OA through   that were encapsulated with sodium alginate. The scaffold
            3D printing facilitates better recovery and maximizes the   promoted chondrocyte proliferation, extracellular matrix
            efficacy of drugs. Wang et al. [112]  designed a thermosensitive   (ECM) deposition, and cell survival (85% cell survival)
            hydrogel  filled with osteoprotegerin  (OPG)  to suppress   in vitro, although it had a significantly lower compressive
            excessive  osteoclast  activity  and  bone  morphogenetic   modulus (20–70 kPa) than human cartilage (700–800 kPa).
            protein-2 (BMP-2) to stimulate osteogenesis. To create   Rathan et al. [117]  developed a cartilage extracellular matrix
            a composite scaffold for implantation, the drug-loaded   (cECM)-functionalized alginate, which was infused into
            hydrogel was injected into a porous Ti6Al4V scaffold   an FDM-printed PCL network to form a scaffold. The
            created by 3D printing. The BMP-2 and OPG released   scaffold significantly enhanced chondrogenic potential

            Volume 9 Issue 4 (2023)                        242                         https://doi.org/10.18063/ijb.732
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