Page 64 - v11i4
P. 64

International Journal of Bioprinting                                3D bioprinting of nerve guidance conduits




            However, despite their innovative vision and current   a promising approach to achieve controlled regulation of
            implementation in clinical studies, these conduits are   the biodegradation rate, mechanical strength, and other
            still limited to small-diameter nerves and may not be   properties of the conduit. This customization allows the
            effective for bridging longer nerve gaps. Advancements   conduit to meet the specific requirements of different types
            in biomaterials and 3D bioprinting technologies  can   of injuries and injury gaps, thereby providing superior
                                                     115
            therefore offer the potential for developing novel nerve   performance in the repair and regeneration of PNIs.
            conduits that address such limitations by incorporating   Although 3D bioprinting has made significant
            bioactive factors to further enhance nerve regeneration,   progress in the fabrication of peripheral NGCs, and
            while offering more complex NGC geometrical structures.   the prospects are bright, many challenges remain. The
            The use of composite biomaterials functionalized with   biomaterials available for printing are limited, and the
            biomolecules or embedded with SCs or NSCs also     performance in terms of degradability, biocompatibility,
            inevitably complicates the certification process. The   and mechanical properties needs to be improved. Future
            regulatory approval typically focuses on certifying the   research on NGCs should focus more on enhancing their
            core biomaterial, such as the scaffold, while the integration   bio-hybridity by controlling the embedment of stem
            of patient-derived cells is subject to separate approval   cells with neurotrophic factors and targeted drugs. This
            processes. Consequently, one of the biggest obstacles at the   strategy aims to further expand the potential for nerve
            moment is regulatory approval. Furthermore, most of the   regeneration, addressing the various needs of nerve repair
            research to date has been based on small animal models,   effectively. In addition, future studies of nerve repair
            which do not fully capture the complexity of human   mechanisms will provide a better direction for the design
            peripheral nerve regeneration. Validation using large   of new 3D-printed NGCs. The integration of bioelectronic
            animal models is necessary to accurately mimic human   interfaces, smart biomaterials, and 4D printing is another
            anatomical and physiological conditions. Ultimately, the   emerging direction in the field of NGCs that has the
            scalability of such prototypes heavily depends on factors   potential to completely transform the next generation
            like batch-to-batch variation, long-term sterility, scalability,   of NGCs. The development of NGCs that adjust to the
            and rigorous quality control, all of which are crucial for   physiological conditions of the regenerating nerve is
            successful product commercialization. For customized or   achievable through 4D printing, which involves the
            multi-material structures, the scalability of bioprinting   generation of dynamic structures capable of responding
            platforms remains a significant challenge. Advancements   to  environmental  stimuli,  such  as  temperature,  pH,  or
            in process automation, closed-loop control systems, and   electrical signals. The regenerative capacity of NGCs
            real-time  quality  assurance  technologies  will  increase   could also be enhanced using smart biomaterials
            their technological availability and market awareness.   engineered to actively release bioactive molecules or
            Within this framework, stronger cooperation between all   exhibit a controlled degradation profile. In addition,
            stakeholders involved,  including  academic  researchers,   bioelectronic interfaces offer the possibility of integrating
            physicians, regulatory agencies, and business partners, is   electrical stimulation within NGCs to stimulate (and
            needed to move forward.
                                                               potentially accelerate)  in situ nerve regeneration.
            6. Conclusion                                      Through  regulating  neuronal  activity,  boosting  axonal
                                                               regeneration, and supporting neuroplasticity, electrical
            NGCs have a broad application prospect in the field of   stimulation has been demonstrated to stimulate nerve
            nerve repair for their ability to construct NTE conduits   growth. Electrical signals can promote cell proliferation,
            using a combination of designs and biomaterials chosen   release neurotrophic factors, and improve the conduit
            to mimic the natural structure of peripheral nerves   regenerating axon alignment. This controlled stimulation
            and provide a favorable microenvironment for nerve   can also support the formation of synaptic connections
            regeneration. Although there are various current solutions,   and improve  functional  recovery  in nerve  tissues.
            most of these conduits are still in the experimental stage   Bioelectronic interfaces could be incorporated into
            and have not reached clinical translation. None of them can   NGCs using biocompatible conductive  materials,
            currently fully substitute autologous nerve grafts to repair   such as poly(3,4-ethylenedioxythiophene) polystyrene
            peripheral nerve defects. Recently, AM has been exploited   sulfonate or graphene, enabling precise control over the
            for the fabrication of multi-material and multi-functional   electrical signals applied. Therefore, the integration of
            NGCs. An ideal 3D-bioprinted personalized NGC should   these technologies promotes the development of highly
            mimic the precise structural details of the nerve region to   customizable, multi-functional NGCs that not only
            be replaced by guiding tissue regeneration. In this concept,   provide structural support but also actively participate in
            biocomposites of natural and synthetic origins are seen as   the nerve regeneration process.

            Volume 11 Issue 4 (2025)                        56                            doi: 10.36922/IJB025140120
   59   60   61   62   63   64   65   66   67   68   69