Recent advances in enhances peripheral nerve orientation: the synergy of micro or nano patterns with therapeutic tactics

Abstract

Several studies suggest that topographical patterns influence nerve cell fate. Efforts have been made to improve nerve cell functionality through this approach, focusing on therapeutic strategies that enhance nerve cell function and support structures. However, inadequate nerve cell orientation can impede long-term efficiency, affecting nerve tissue repair. Therefore, enhancing neurites/axons directional growth and cell orientation is crucial for better therapeutic outcomes, reducing nerve coiling, and ensuring accurate nerve fiber connections. Conflicting results exist regarding the effects of micro- or nano-patterns on nerve cell migration, directional growth, immunogenic response, and angiogenesis, complicating their clinical use. Nevertheless, advances in lithography, electrospinning, casting, and molding techniques to intentionally control the fate and neuronal cells orientation are being explored to rapidly and sustainably improve nerve tissue efficiency. It appears that this can be accomplished by combining micro- and nano-patterns with nanomaterials, biological gradients, and electrical stimulation. Despite promising outcomes, the unclear mechanism of action, the presence of growth cones in various directions, and the restriction of outcomes to morphological and functional nerve cell markers have presented challenges in utilizing this method. This review seeks to clarify how micro- or nano-patterns affect nerve cell morphology and function, highlighting the potential benefits of cell orientation, especially in combined approaches. Graphical Abstract

Recent perspectives on the synergy of mesenchymal stem cells with micro/nano strategies in peripheral nerve regeneration-a review

“…In essence, M1 macrophages kickstart the healing process in the initial three to 5 days by clearing debris and pathogenic contamination through phagocytosis and secreting TNFα, IL-1α and IL-1β and metalloproteinase ( Liu et al, 2019 ). Subsequently, the transition of M1 macrophages to M2 macrophages and the release of anti-inflammatory cytokines like IL-4/IL-13 and IL-10 promote activities such as proliferation, maturation, migration, resolution of inflammation, and angiogenesis ( Boukelmoune et al, 2021 ; Sharifi et al, 2024 ).…”

“…Studies have shown promising results using MSCs to regenerate peripheral nerves in synergy with therapeutic techniques such as drug therapy, cell therapy, and electrical stimulation ( Zuo et al, 2020 ; Supra et al, 2023 ; Sharifi et al, 2024 ). However, technical challenges make it difficult to implement synergistic approaches.…”

Engineering cell-derived extracellular matrix for peripheral nerve regeneration

“…It is imperative to develop new feasible nerve grafts as alternatives for the treatment of PNI. With the development of material science and tissue engineering, numerous artificial nerve grafts made by various synthetic and natural biomaterials have been devised [ [8] , [9] , [10] ]. Because of their low cell affinity and poor hydrophilicity, synthetic biomaterials are difficult to obtain neurotherapeutic functions comparable to natural biomaterials, and have therefore been gradually replaced by the latter [ 11 , 12 ].…”