Page 237 - IJB-10-2
P. 237

International Journal of Bioprinting                       G40T60@WNT5A promotes osteoblast differentiation




            1. Introduction                                    a platform for improving the compatibility of prostheses
                                                               with bone defects and enabling the  restoration of
            Chronic osteomyelitis is a serious complication of   bone stability. 19-21  Varying degrees of bone defects are
            orthopedic surgery.  After the surgery, the severe damage   the  frequently  encountered challenges  in bone  joint
                           1
            to the periosteum at the lesion caused by inflammation   remodeling surgeries.  Nevertheless, 3D-printed models
            weakens the ability to form bone, leading to bone necrosis   could help restore the anatomical structure of bone
                                       2
            and long-segment bone defects.  Chronic osteomyelitis   joints and assist surgeons to better understand the 3D
            presents with extensive scarring, sinuses, necrotic bone,   morphology of bone joints, in addition to other apparent
            and dead spaces. Adding to the severity of the condition   advantages such as increased efficiency and stability of
            is the poor local blood circulation, which restricts   prosthetic matching and reduced surgical difficulty.
                                                                                                            22
            antimicrobial drugs to reach the affected area, thereby   Besides, surgeons may formulate treatment plans, perform
            promoting bacterial growth and subsequently leading to   surgical rehearsal, and conduct evaluation using these
            recurrent infections. Thus, these issues pose a challenge in   models. Therefore, 3D printing stands as an obvious
            clinical practice.  Chronic osteomyelitis usually occurs in   solution in the creation of customized prosthetics in the
                         3-5
            adults and is typically secondary to open bone injuries or   case of significant bone defects.  Recently, owing to their
                                                                                        23
            bone reconstruction surgery. 6,7
                                                               favorable biocompatibility and bioactivity, there has been
               In 1965, Gavriil Ilizarov proposed a theory known   growing interest in biodegradable materials, which are
            as “tension-stress principle,” based on which the Ilizarov   used to promote bone tissue regeneration and repair.
            technique for bone sliding was conceptualized, which has   Biodegradable  polymers  have  been  widely applied  in
            been the preferred method for treating tibial bone defects   various functions, such as drug delivery,  biomedicine,  3D
                                                                                              24
                                                                                                         25
            and  nonunion  since  then. 8-11   Surgical  debridement  and   printing,  food packaging,  enzyme immobilization, tissue
                                                                      26
                                                                                    27
            bone grafting are conventional approaches for treating   engineering scaffolds, nanotechnology, and technological
            chronic osteomyelitis with bone defects. However, for   applications.  Biodegradable polymers can be generally
                                                                         28
            patients with longer defect lengths, the difficulty in bone   classified into  two  categories:  synthetic polymers  and
            reconstruction is increased due to significant bone loss,   natural polymers.  Synthetic polymers are compatible
                                                                              29
            resulting  in  often  unsatisfactory  patient  outcomes.   The   with the human body, can undergo biodegradation, and
                                                     12
            Masquelet technique could produce a satisfactory induced   can be easily transformed into different 3D structures. On
            membrane when bone cement is placed on the infection-  the other hand, natural polymers can be metabolized into
            free surgical area, targeting bone defects caused by   utilizable metabolites or easily cleared by the kidneys. A
            thorough debridement and various factors. 13,14  Moreover,   few noteworthy advantages of biodegradable polymers
            the implantation of autologous bone has relatively fewer   include reduced inflammatory reactions, non-toxicity,
            limitations in terms of length, which gives it a significant   and the ability to degrade enzymatically in the body.  He
                                                                                                         30
            advantage over other techniques when dealing with large   et al. discovered that 3D-printed biodegradable PU/
            segmental bone defects. The implantation of autologous   PAAM/Gel hydrogel scaffolds exhibit high flexibility
            bone also enhances patients’ medical experience and   and adaptive capacity for irregular defects, making them
            facilitates nursing care and rehabilitation. 14-16  However,   suitable for non-load-bearing bone regeneration.  Chen et
                                                                                                      31
            several limitations of using traditional Masquelet technique   al. found that 3D-printed scaffolds can direct extracellular
            in bone cement filling should be acknowledged. In the   matrix/stromal stem cells for bone and cartilage
            traditional in vivo shaping method, the bone defect is filled   defect regeneration. 32
            with bone cement before it solidifies and wraps around the   According to previous research, WNT5A is closely
            fracture ends for natural solidification. The solidification   related to  osteogenic  differentiation.  Some studies  have
            process is started during the second stage surgery once   reported that microvesicles derived from adipocytes could
            the bone cement becomes firmly connected to the bone   inhibit osteogenic differentiation by secreting miR-148a,
            ends;  however,  given  its  relatively  large size, removal  of   which targets and regulates the Wnt5a/Ror2 pathway. 33-36
            the bone cement would introduce damages to the induced   In addition, it was found that activation of Wnt5a could
            membrane and the interface between the bone cement and   mediate the mechanical stretch-induced osteogenic
            bone tissue, thus affecting fracture healing in the second-  differentiation of mesenchymal stem cells.  WNT5A is
                                                                                                  37
            stage bone grafting. Additionally, the heat released during   also associated with angiogenesis. Research has found that
            the solidification process of the bone cement can also   antagonizing the Wnt/β-catenin signaling pathway could
            damage adjacent bone and tissues. 17,18
                                                               inhibit endothelial cell proliferation, tube formation, and
               With the increasing application of three-dimensional   migration as well as induce endothelial cell apoptosis,
            (3D) printing in orthopedics, this technology provides   thereby suppressing endothelial cell angiogenesis. 38


            Volume 10 Issue 2 (2024)                       229                                doi: 10.36922/ijb.1461
   232   233   234   235   236   237   238   239   240   241   242