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Open research questions in Nerve injury and regeneration

28 unresolved questions extracted from the limitations and future-work sections of 204 Nerve injury and regeneration papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Paclitaxel-induced peripheral neuropathy (PIPN) is the most common dose-limiting side effect of paclitaxel chemotherapy, yet the relationship between structural damage to peripheral nerve terminals and functional impairment of nociceptors has not been directly examined.

    Peripheral sensory terminal degeneration is linked to sensory fiber hyperexcitability in paclitaxel-induced peripheral neuropathy · 2026 · DOI

  • Previous studies have shown that stiffness of CNS implants significantly affects glial encapsulation, but few studies have investigated materials that truly match brain tissue stiffness.

    Mechanically Compliant, Precision-Porous Brain Implants Reduce the Foreign Body Reaction and Guide Regeneration · 2026 · DOI

  • Local cortisol regeneration via 11β-hydroxysteroid dehydrogenase (11β-HSD1) is elevated in diabetic skin, but the direct effects of cortisol on dermal fibroblast behaviour under diabetic conditions remain unclear.

    FP01 Cortisol modulation of dermal fibroblast migration and early fibrotic markers in diabetic wounds · 2026 · DOI

  • While mature peripheral axons retain an intrinsic capacity for regeneration, successful reinnervation of target tissues is limited by antagonistic molecular factors in the injury microenvironment such as the ErbB family member, EGFR.

    The Small Molecule EGFR Inhibitor Erlotinib Accelerates Axon Outgrowth And Functional Recovery, And Increases LAR Expression Following Peripheral Nerve Injury · 2026 · DOI

  • multimodal approaches aimed at restoring motor and sensory function while preserving neuromuscular junctions to avoid neurogenic atrophy and to support reinnervation after prolonged denervation (Lopes et al., 2025b). therapy will To facilitate the standardization of PNI, classification systems have been proposed (Alvites et al., 2018; Lopes et al., 2025b; Alvites et al., 2021). The most widely used schemes are those of Seddon and three categories: neuropraxia, Sunderland. Seddon defined axonotmesis, and neurotmesis, based on demyelination, axonal injury, and the extent of connective tissue disruption (Lopes et al., 2022; Alvites RD. et al., 2022). Sunderland further refined this model into five degrees of injury: first degree neuropraxia, fifth degree neurotmesis, and three intermediate degrees derived from axonotmesis, depending on the involvement of endoneurium, perineurium, and epineurium (Lopes et al., 2022; Alvites et al., 2020). Later, Mackinnon introduced a sixth degree to account for mixed injuries, which are probably the most common in clinical practice (Lopes et al., 2022). Following PNI, a sequence of degeneration and regeneration occurs (Gu et al., 2024). This process involves resolution of the inflammatory response, production of neurotrophic factors, axonal regrowth, and neuronal survival (Wu et al., 2025). Schwann cells are central in the regeneration process, as they proliferate and align into Büngner bands, producing neurotrophic and adhesion molecules that guide axonal growth and remyelination (Jiang et al., 2024). However, regeneration is inherently slow, leading to prolonged denervation of target organs and muscles, often resulting in irreversible atrophy and loss of function (Talsma et al., 2024). This underlines the need for timely and effective therapeutic interventions. In severe injuries such as neurotmesis, end-to-end (EtE) suturing remains the treatment of choice when tension-free approximation of nerve stumps is possible (Alvites et al., 2017). If not feasible, autologous nerve grafting is considered the gold standard (Lopes et al., 2022). However, it is limited by donor site morbidity, functional loss, and the challenge of obtaining grafts of Frontiers in Cell and Developmental Biology 02 frontiersin.org Lopes et al. 10.3389/fcell.2026.1778085 adequate size and characteristics (Ni et al., 2023). To overcome the limitations associated with autologous grafts, multiple approaches have been explored to support peripheral nerve regeneration, aiming to stimulate axonal growth and improve functional recovery after PNI (Alvites et al., 2021; Shen et al., 2022; Sousa et al., 2024).

    Stem cell-derived secretome and dental pulp stem cells enhance sciatic nerve regeneration in a rat sciatic neurotmesis model using chitosan nerve conduits · 2026 · DOI

  • The role of surrounding tissues in dendrite regeneration is poorly characterized, especially considering that neuronal injury is typically accompanied by broad tissue damage.

    Epidermal and ECM Damage Following Pinch Injury Restricts Dendrite Regeneration in Drosophila · 2026 · DOI

  • However, the effects of immunosuppressive drugs on neurite outgrowth and axonal regeneration, processes critical for neural circuit reconstruction, have not been fully characterized.

    Clinical Relevant Immunosuppressive Drugs Differentially Modulate Axonal Outgrowth from Human Stem Cell Derived Neurons · 2026 · DOI

  • The underlying mechanisms of survival and regeneration for these nerves remain unclear, and elucidating the molecular processes involved may inform the development of targeted therapies to optimize outcomes in nerve injury and repair.

    Comparative Motor Neuron Survival Following Facial And Sciatic Nerve Transection And Repair In A Mouse Model · 2026 · DOI

  • Nerve guidance conduits (NGCs) are considered as promising treatment strategy and frontier trend for peripheral nerve regeneration, while their therapeutic outcomes are limited by the lack of controllable drug delivery and available physicochemical cues.

    Ultrasound‐Responsive Aligned Piezoelectric Nanofibers Derived Hydrogel Conduits for Peripheral Nerve Regeneration · 2024 · DOI

  • However, the simple administration of GFs is insufficient for reconstructing PNI due to their short half‑life and rapid deactivation in body fluids.

    Growth factors-based therapeutic strategies and their underlying signaling mechanisms for peripheral nerve regeneration · 2020 · DOI

  • Immunofluorescent sig- nal for phosphacan and neurocan was more intense in astro- cytes close to the injury site, while brevican was scarcely present in cultured astrocytes.

    Real-Time PCR and Immunocytochemical Study of Chondroitin Sulfate Proteoglycans after Scratch Wounding in Cultured Astrocytes / PCR I IMUNOCITOHEMIJSKA STUDIJA EKSPRESIJE HONDROITIN-SULFATNIH PROTEOGLIKANA NAKON POVREDE ASTROCITA U KULTURI · 2013 · DOI

  • Conclusion: The results of the present study suggest that the use of a constant method in order to compose a nerve graft group in experimental studies may be convenient to avoid contradictory results among the researches.

    Is Standardization of Nerve Graft Groups Necessary for Experimental Studies? · 2011 · DOI

  • And the high rate of incidence of nerve injuries in war wounds would seem to have given an opportunity for the further investigation of nerve suture.

    The Repair of Nerves by Suture · 1951 · DOI

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28 open questions have been extracted from the limitations and future-work passages of 204 Nerve injury and regeneration papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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