As the authors detail, PNI is a prevalent neurological condition that often causes permanent sensory and motor dysfunction, severely impairing patient's quality of life. While autologous nerve grafts remain the clinical gold standard for long-segment nerve defects, they are plagued by critical limitations including scarce donor tissue, donor site morbidity, and size mismatch between graft and host nerve. Existing artificial nerve guidance conduits (NGCs) also face significant hurdles: their fixed tubular structures fail to adapt to the variable diameters and irregular geometries of natural nerves, and their reliance on microsuturing for fixation demands advanced surgical skills, carries risks of iatrogenic injury, inflammation, and scar formation, and is nearly unfeasible in anatomically confined surgical spaces.
Drawing inspiration from how pinecone scales close in humid environments due to differential water absorption and swelling between their inner and outer layers, the research team designed an asymmetric composite film (PU/PGAX) combining hydrophobic polyurethane (PU) and hydrophilic γ-polyglutamic acid (PGA). As the authors explain, during rapid high-temperature drying, the surfactant properties of quaternary ammonium salts in the PU drive it to enrich the film top surface, while PGA accumulates at the bottom, creating a distinct hydrophilic-hydrophobic gradient. When exposed to water or physiological saline, the hydrophilic PGA layer rapidly swells while the hydrophobic PU layer remains structurally stable, and this swelling differential autonomously drives the flat film to curl into a tubular structure within seconds, mimicking the pinecone's shape-shifting behavior. By coating the film with a biocompatible PU adhesive emulsion, the team endowed the conduit with robust tissue adhesion, enabling it to adaptively wrap around severed nerve stumps and achieve secure fixation without a single suture.
The authors identified that the PU/PGA₁₀ formulation, containing 10% PGA, delivered optimal performance: it reached a maximum bending curvature of 1.02 mm-1 within 90 seconds of water immersion, conformed seamlessly to tubular structures with diameters ranging from 3 to 10 mm to match varying nerve sizes, and achieved a shear adhesion strength of 24.3 kPa to porcine skin. In vitro experiments confirmed the conduit's excellent cytocompatibility, with no observed cytotoxicity to rat Schwann cells, and it significantly enhanced Schwann cell migration—a critical process for nerve regeneration. Notably, the material also exhibited immunomodulatory effects, suppressing pro-inflammatory cytokine release and promoting the polarization of macrophages toward the pro-repair M2 phenotype to create a favorable regenerative microenvironment.
In a rat model of 8 mm sciatic nerve defect, the gold standard for preclinical nerve repair research, the PU/PGA10 conduit achieved robust nerve regeneration and functional recovery, as the authors detail. Ten weeks after surgery, the treated rats showed significant improvement in the sciatic function index (SFI), a key metric of motor function recovery, compared to the untreated control and pure PU patch groups. Transmission electron microscopy and histological analysis revealed that the conduit supported robust axonal regeneration, with significantly larger axon diameters and thicker myelin sheaths than the PU patch group, approaching the repair efficacy of autologous nerve grafts. The treatment also effectively mitigated gastrocnemius muscle atrophy and fibrosis, a common secondary complication of long-term denervation.
The authors emphasize that this pinecone-inspired conduit addresses longstanding unmet needs in PNI repair, offering straightforward operability, adaptive tissue matching, and suture-free fixation that eliminates secondary iatrogenic damage. They note that the technology also holds promise for tissue repair in other surgically confined, hard-to-suture anatomical sites, with future research focused on establishing a quantitative structure-property model to precisely tailor the conduit's curling dynamics and curvature for customized clinical applications, ultimately advancing the translation of this innovative technology from the lab to patient care.
Authors of the paper include Xiaolei Guo, Jinwei Li, Hongyu Xu, Shengrong Long, Junhong Li, Ao Wang, Wenkai Liu, Fan Zhang, Zhen Li, Feng Luo, Jiehua Li, Yanchao Wang, Hong Tan, and Ting Lan.
This work was supported by the National Natural Science Foundation of China (52433015, 52373296, 52473138, and 52173287), the State Key Laboratory of Polymer Materials Engineering (sklpme2022-2-07), and the Outstanding Youth Foundation of Sichuan Cancer Hospital & Institute (Grant no. YB2025004).
The paper, "Pinecone-Inspired Water-Responsive Curling Adhesive Conduit for Peripheral Nerve Repair" was published in the journal Cyborg and Bionic Systems on Mar. 27, 2026, at DOI: 10.34133/cbsystems.0556.
