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1. Advances in Biomimetic Nerve Guidance Conduits for Peripheral Nerve Regeneration

   https://doi.org/10.3390/nano13182528  

   Mankavi, Faranak; Ibrahim, Rana; Wang, Hongjun (September 2023, Nanomaterials)

   Injuries to the peripheral nervous system are a common clinical issue, causing dysfunctions of the motor and sensory systems. Surgical interventions such as nerve autografting are necessary to repair damaged nerves. Even with autografting, i.e., the gold standard, malfunctioning and mismatches between the injured and donor nerves often lead to unwanted failure. Thus, there is an urgent need for a new intervention in clinical practice to achieve full functional recovery. Nerve guidance conduits (NGCs), providing physicochemical cues to guide neural regeneration, have great potential for the clinical regeneration of peripheral nerves. Typically, NGCs are tubular structures with various configurations to create a microenvironment that induces the oriented and accelerated growth of axons and promotes neuron cell migration and tissue maturation within the injured tissue. Once the native neural environment is better understood, ideal NGCs should maximally recapitulate those key physiological attributes for better neural regeneration. Indeed, NGC design has evolved from solely physical guidance to biochemical stimulation. NGC fabrication requires fundamental considerations of distinct nerve structures, the associated extracellular compositions (extracellular matrices, growth factors, and cytokines), cellular components, and advanced fabrication technologies that can mimic the structure and morphology of native extracellular matrices. Thus, this review mainly summarizes the recent advances in the state-of-the-art NGCs in terms of biomaterial innovations, structural design, and advanced fabrication technologies and provides an in-depth discussion of cellular responses (adhesion, spreading, and alignment) to such biomimetic cues for neural regeneration and repair. 

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2. Symmetries of the cyclic nerve

   https://doi.org/10.1016/j.aim.2025.110170  

   Ayala, David; Mazel-Gee, Aaron; Rozenblyum, Nick (April 2025, Advances in Mathematics)

   We undertake a systematic study of the Hochschild homology, i.e. (the geometric realization of) the cyclic nerve, of -categories (and more generally of category-objects in an ∞-category), as a version of factorization homology. In order to do this, we codify -categories in terms of quiver representations in them. By examining a universal instance of such Hochschild homology, we explicitly identify its natural symmetries, and construct a non-stable version of the cyclotomic trace map. Along the way we give a unified account of the cyclic, paracyclic, and epicyclic categories. We also prove that this gives a combinatorial description of the case of factorization homology as presented in [4], which parametrizes -categories by solidly 1-framed stratified spaces. 

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3. Aging Effects on Optic Nerve Neurodegeneration

   https://doi.org/10.3390/ijms24032573  

   Coleman-Belin, Janet; Harris, Alon; Chen, Bo; Zhou, Jing; Ciulla, Thomas; Verticchio, Alice; Antman, Gal; Chang, Michael; Siesky, Brent (February 2023, International Journal of Molecular Sciences)

   Common risk factors for many ocular pathologies involve non-pathologic, age-related damage to the optic nerve. Understanding the mechanisms of age-related changes can facilitate targeted treatments for ocular pathologies that arise at any point in life. In this review, we examine these age-related, neurodegenerative changes in the optic nerve, contextualize these changes from the anatomic to the molecular level, and appreciate their relationship with ocular pathophysiology. From simple structural and mechanical changes at the optic nerve head (ONH), to epigenetic and biochemical alterations of tissue and the environment, multiple age-dependent mechanisms drive extracellular matrix (ECM) remodeling, retinal ganglion cell (RGC) loss, and lowered regenerative ability of respective axons. In conjunction, aging decreases the ability of myelin to preserve maximal conductivity, even with “successfully” regenerated axons. Glial cells, however, regeneratively overcompensate and result in a microenvironment that promotes RGC axonal death. Better elucidating optic nerve neurodegeneration remains of interest, specifically investigating human ECM, RGCs, axons, oligodendrocytes, and astrocytes; clarifying the exact processes of aged ocular connective tissue alterations and their ultrastructural impacts; and developing novel technologies and pharmacotherapies that target known genetic, biochemical, matrisome, and neuroinflammatory markers. Management models should account for age-related changes when addressing glaucoma, diabetic retinopathy, and other blinding diseases. 

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4. A 3D Nerve Guidance Conduit Surface With a Wrinkled Protein Coating Toward Peripheral Nerve Injury Repair

   https://doi.org/10.1002/pat.70003  

   Oguntade, Elizabeth; Agyapong, Johnson_N; O'Grady, Kerrin; Henderson, James_H (November 2024, Polymers for Advanced Technologies)

   ABSTRACT Peripheral nerve injuries (PNIs) resulting in myelin breakdown and axonal degeneration at both the proximal and distal nerve stumps are major clinical concerns that can induce functional loss and diminished quality of life. In biomaterials science, considerable attention has been given to artificial nerve guidance conduits (NGCs), since the engineered tubular structures have the potential to supply a supportive nerve microenvironment to longitudinally align the regenerating axons for bridging the injured nerve sites. Although NGCs may become promising alternatives to nerve autografts, the fabrication approaches available to incorporate directional cues for dictating neuronal behavior and nerve reconnection have been limited to conventional micro/nano‐fabrication techniques that are complex and time‐consuming due to manual processing steps. Thus, our goal here was to develop a simple manufacturing approach for introducing topographical cues onto NGCs. To achieve this goal, we used an established mechanically actuated silk wrinkling approach to create topographically functionalized surfaces as a potential NGC material platform for guided directional alignment of neurons. We 3D‐printed thermo‐responsive shape‐memory polymer (SMP)‐based NGCs that can produce silk fibroin (SF)‐wrinkled topographies on the micro and nano‐meter length scale. Since SF is a commonly used biomaterial surface coating with excellent neuro‐compatibility, we studied the ability to develop NGCs that can autonomously actuate silk wrinkles upon heat‐induced contraction of the SMP and evaluated the effects of the topographically functionalized construct on neuronal behavior. Using an immortalized dorsal root ganglion neuronal cell line, we found that the silk‐wrinkled conduits displayed high neuronal viability and adhesion compared to uncoated conduits and tissue‐culture polystyrene controls. We also found that the wrinkled conduits enabled the neurons to elongate and align parallel to the direction of the wrinkled topography. Longer neurite extension was also observed on the wrinkled conduits compared to their respective controls. These findings demonstrate the potential for functional wrinkled protein coatings to provide directional cues in the fabrication of artificial NGCs for peripheral nerve repair. 

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5. Decellularized Biohybrid Nerve Promotes Motor Axon Projections

   https://doi.org/10.1002/adhm.202401875  

   Mehta, Abijeet_Singh; Zhang, Sophia_L; Xie, Xinran; Khanna, Shreyaa; Tropp, Joshua; Ji, Xudong; Daso, Rachel_E; Franz, Colin_K; Jordan, Sumannas_W; Rivnay, Jonathan (September 2024, Advanced Healthcare Materials)

   Abstract Developing nerve grafts with intact mesostructures, superior conductivity, minimal immunogenicity, and improved tissue integration is essential for the treatment and restoration of neurological dysfunctions. A key factor is promoting directed axon growth into the grafts. To achieve this, biohybrid nerves are developed using decellularized rat sciatic nerve modified by in situ polymerization of poly(3,4‐ethylenedioxythiophene) (PEDOT). Nine biohybrid nerves are compared with varying polymerization conditions and cycles, selecting the best candidate through material characterization. These results show that a 1:1 ratio of FeCl₃oxidant to ethylenedioxythiophene (EDOT) monomer, cycled twice, provides superior conductivity (>0.2 mS cm⁻¹), mechanical alignment, intact mesostructures, and high compatibility with cells and blood. To test the biohybrid nerve's effectiveness in promoting motor axon growth, human Spinal Cord Spheroids (hSCSs) derived from HUES 3 Hb9:GFP cells are used, with motor axons labeled with green fluorescent protein (GFP). Seeding hSCS onto one end of the conduit allows motor axon outgrowth into the biohybrid nerve. The construct effectively promotes directed motor axon growth, which improves significantly after seeding the grafts with Schwann cells. This study presents a promising approach for reconstructing axonal tracts in humans. 

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