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International Journal of Bioprinting                                     Applications of 3D printing in aging



            group of people, and its incidence is closely related to aging   properties and biocompatibility are the best alternatives,
            and obesity, with the WHO reporting that about 1 in 10   but often do not integrate well into the recipient site due to
            middle-aged and elderly people over the age of 60 suffer   the lack of a natural tissue-mimicking structure. Therefore,
            from OA. One of the most significant risk factors for OA is   3D printing technology is used to produce bones that
            aging . Studies have shown that the incidence of OA with   can more closely resemble their natural counterpart. The
                [92]
            imaging changes and painful symptoms increases with age.   high degree of personalization and design freedom make
            The lesions involve structural changes in articular cartilage,   3D printing well-suited for the manufacturing of bone
            subchondral bone, synovial membrane, and periarticular   grafts. The personalized and customized bioprostheses for
            muscles, mainly manifesting as bone friction, morning   transplantation becomes a better option to suit the needs
            stiffness, joint motion disorders, and deformities in   of different patients.
            appearance, which all bring great pain and inconvenience
            to patients [93,94] . At the same time, OA also causes social   The main materials used for bone tissue engineering
            burdens . On the one hand, the disability caused by OA   include metals, ceramics, and biopolymers. Titanium-
                  [95]
            and its consequences lead to a reduction in the workforce;   based scaffolds are frequently utilized as implant materials
            on the  other hand, the  treatment  for OA is  long-lasting   for treating bone defects. However, the inefficient
            and expensive, which imposes heavy financial burden to   osseointegration of typical titanium-based implants is
            the healthcare system . The main treatment principle for   frequently observed, which is caused by the misaligned
                             [96]
            OA is to reduce symptoms and slow the progression of the   biomechanics and poor bioactivity of these implants. To
            disease, but eventually, more severe OA can only be treated   address  this  issue, Ma  et al. [104]   used  SLM  to  3D-print  a
            with joint replacement [97,98] .                   hybrid scaffold made of Ti-6Al-4V alloy and GelMA with
               At present, studies on the pathogenesis of OA suggest   dual  bionic  properties  (GMPT)  for  bone  defect  repair.
            that it is mainly related to the imbalance in the metabolic   Because of the special dual bionic design, the synthetic
            homeostasis of cartilage, subchondral osteosclerosis,   GMPT scaffold replicated the microstructure and
            and synovial inflammation. Synovial is a special type of   mechanical characteristics of natural cancellous bone and
            transparent tissue at the skeletal surface of the joint which   had superior osteogenic and angiogenic qualities compared
            facilitates the sliding of the joint surface and reduces   to the porous TC4 metal scaffold. Ceramic materials have
            friction during movement. One distinctive feature of   similar mechanical properties to bones and are used
                                                                                                  [105]
            OA is the loss of articular cartilage, which generally   widely in bone tissue engineering. Wu et al.   developed
            attribute to the imbalance between the anabolism and   a novel two-layer scaffold for bone repair using calcium-
            catabolism of chondrocytes. Aging, obesity, and changes in   deficient hydroxyapatite (CDHA) and poly(lactic-glycolic
            biological rhythms cause the hypertrophy or apoptosis of   acid copolymer) (PLGA). An optimized mix of CDHA
            chondrocytes, metabolic disorders, and cellular senescence   and  PLGA with  good  biocompatibility  and negligible
            that disrupt cartilage homeostasis, thus triggering OA.   cytotoxicity was 3D-printed by DIW to create a bilayer
            Subchondral bone remodeling and bone redundancy    scaffold. Studies in animal models showed successful
            formation are  important features  of  OA.  Meanwhile,   implantation of the scaffold and significant osteogenic
                                                                                                           [106]
            increased subchondral bone angiogenesis and vascular   ability within 6 months (Figure 3A and B). Van hede et al.
            invasion of avascular cartilage are early diagnostic features   used SLA to 3D-print bioceramic-resin composite to
            of OA . Aging plays crucial roles in the development of   fabricate a gyratory scaffold. The scaffold was implanted into
                 [99]
            OA.  Chondrocyte  loss  and  cartilage  and  joint  damages   rats, and a significant increase in bone volume within the
            occur during aging process, during which senescent   scaffold was observed after 8 weeks, showing excellent bone
                                                                                                           [107]
            cells accumulate in cartilage tissue and form senescence-  regeneration  properties  (Figure  3C).  Guillaume  et al.
            associated secretory phenotypes through the secretion of   3D-printed  polytrimethylene  carbonate  (PTMC)/
            cytokines, and eventually lead to pathological changes in   hydroxyapatite (HA) scaffolds by photo-crosslinking
            articular cartilage aging [100-103] .              20 wt% HA nanoparticles with PTMC resin using SLA.
                                                               In PTMC/HA scaffolds, the SLA process promoted the
            (A) The role of 3D printing in the treatment and   superficial enriching of HA, which significantly improved
            research of bone diseases                          bone regeneration and promoted osteogenesis (Figure 3D).
            Fractures and bone defects due to osteoporosis and tubular   Zhang  et al. [108]  used digital light processing (DLP) to
            arthritis are usually treated with bone grafting, where the   prepare large-sized (length >150 mm) HA bioceramics
            structures and functions of bones are reconstructed by   with highly microporous surface structure using urethane
            customized grafts. Existing autograft and allograft methods   acrylate (UA) mixed with poly(ethylene glycol) diacrylate
            have many problems, such as limited supply and dangerous   (PEGDA) and HA as a photosensitive composite.
            complications. Bioactive materials with strong mechanical   Experiments showed that the bioceramics have good

            Volume 9 Issue 4 (2023)                        240                         https://doi.org/10.18063/ijb.732
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