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International Journal of Bioprinting                                  3D printing technology in neurotrauma




               In terms of cellular composition,  the nervous system   Peripheral nerve injury (PNI) is one of the most
            is characterized by functionally specialized neurons and   common neuropathies, which is often caused by diseases,
            unique glial cell types.  Neurons act to conduct electrical   accidents,  and  natural disasters.  It  has been  reported
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            signals, and glial cells are mainly responsible for the   that there are more than 20 million patients diagnosed
            stability and development of the nervous system, which   with PNI every year in the United States and more
            are arranged alongside neurons. In addition, glial cells   than 300,000 patients diagnosed with PNI every year in
            can  provide  metabolic  support  to  neurons  and  promote   Europe. 21,22  PNI often affects neural signal transduction,
            the survival, differentiation, and outgrowth of neurons.    leading to the loss of sensory and motor function and
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            Furthermore, the extracellular matrix (ECM), synthesized   even causing disability in patients. Unlike the CNS, the
            and secreted by cells, is indispensable in the nervous   PNS has an intrinsic ability of regeneration. 23,24  After
            system. The ECM of the nervous system is made up of   an injury, Wallerian degeneration occurred at the distal
            three parts: the basement, a diffuse interstitial portion, and   end of the injured sites, and the debris was cleared by
            perineuronal net (PNN).  PNN is a special component of   Schwann cells and phagocytes. 25,26  Meanwhile, Schwann
                                6
            ECM in the nervous system, contributing to maintaining   cells would proliferate and migrate rapidly to form the
            the newly appointed neuronal connections and neuronal   Bungner band, and the growth cone could advance
            protection while concurrently inhibiting synaptic plasticity   toward the distal end. However, in severe cases of PNI,
            and neural regeneration with certain components like   especially long-segmental PNI, the self-regeneration
            CSPGs.  Besides, there are other crucial components,   of the peripheral nerves is unable to realize the re-
                  7,8
            such as chemotropic and neurotrophic factors, in the ECM   connection of the injured nerves. 27,28  At present, the
            of the nervous system.                             functional recovery of long-segmental PNI remains
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            1.2. Neurotrauma                                   challenging in regenerative medicine. Autografts have
            Neurotrauma is an emergency situation and refers to injuries   been considered the gold standard for the clinical
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            that involve the CNS and PNS. CNS injuries mainly include   treatment  of  PNI,   but  this  strategy  is  still  restricted
            traumatic brain injury (TBI) and spinal cord injury (SCI).   by inadequate nerve donors, donor site morbidity, and
            TBI is defined as an alteration in brain function, or other   secondary trauma. Recently, nerve guide conduits derived
            evidence of brain pathology, caused by an external force. It   from synthetic and/or natural materials have been
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            can be divided into mild, moderate, and severe injuries.    developed as promising alternatives for PNI treatment.
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            With 50 million new cases of mild TBI and 2 million new   With a tube-like structure, a conduit can provide physical
            cases  of  moderate and  severe  TBI being  reported every   support and directional guidance for nerve regeneration.
            year worldwide, TBI has emerged as a global public health   Currently, several conduits have been approved by the
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            problem.  The absence of effective treatments poses a   Food and Drug Administration (FDA) for PNI repair. 21,30
            challenge to the management of TBI. Despite advances in   However,  the  therapeutic  efficacy  of  these  conduits  for
            preoperative measures and intensive care, TBI still results   long-segmental PNI is still unsatisfactory and needs to
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            in high mortality and long-term neurological deficits.  In   be improved.
            addition to the primary injury, secondary injuries such as   Recently, some new treatment approaches, including
            inflammatory reaction, reduction of neural cells, and glial   gene therapy, electrical stimulation, electrochemical
            scar formation may occur after TBI.  In recent years, the   neuromodulation  therapy,  and  stem cell  therapy,  have
                                         13
            emergence of stem cell therapy and tissue engineering has   been used for neurotrauma treatment.  However, these
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            provided new strategies for neural network reconstruction   strategies can still not provide an ideal microenvironment
            after TBI. 14,15  However, the delivery and survival of stem   for repairing nervous system injuries, which can resemble
            cells to the injured sites still face significant challenges.   the physical and biological characteristics of natural
            SCI is characterized by damage to the spinal cord, which   tissues, such as the anatomical structure, the diversities of
            breaks nerve  contact between  the brain and the rest of   cells and bioactive substances, and the spatial distribution
            the body, leading to temporary or permanent functional   of the bioactive components.
            impairment.  Approximately 500,000 individuals suffer
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            from SCI worldwide every year, resulting in a huge   1.3. 3D printing and 3D bioprinting technology
            socioeconomic burden.  Currently, treatment options for   3D printing is an additive manufacturing process that
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            SCI encompass surgical interventions, pharmaceutical   creates unique 3D constructs by building 3D structures
            approaches, hypothermia, and rehabilitative medical care.    layer by layer from computer-aided design (CAD)
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            Nevertheless, the effectiveness of these treatments is limited,   models. 3D printing combined with 3D imaging
            and the prognosis for individuals with SCI is poor.    technology  and robot-based  precision biofabrication
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            Volume 10 Issue 3 (2024)                        62                                doi: 10.36922/ijb.2311
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