PLA/PCL Tubes Filled with Polysaccharide Hydrogels as Robust Hybrid Nerve Guidance Conduits with Controlled Swelling

Peripheral nerve injuries (PNIs) cause severe loss of motor and sensory functions, with limited recovery achievable through current surgical options. Nerve guidance conduits (NGCs) represent a promising alternative for bridging nerve gaps, particularly when integrating bioactive and mechanically stable components. In this study, a multi-component NGC is developed by combining rolled-up poly(lactic acid)/poly(caprolactone) (PLA/PCL) microfilms, providing mechanical reinforcement and shape-memory behavior, with polysaccharide-based hydrogels (alginate (ALG), hyaluronic acid (HA), or carboxymethyl cellulose (CMC)) that act as lumen fillers to mimic the extracellular matrix (ECM). The hydrogel formulations display appropriate viscosity, straightforward gelation, and enhanced mechanical properties while maintaining cytocompatibility. Although all three composite conduits exhibit non-toxic degradation by-products and mechanical performance comparable to that of native human nerves, the NGC containing the HA click-hydrogel displays a more porous structure, with an elastic modulus of 19.2 ± 2.9 kPa and ultimate compressive strength of 29.2 ± 8.2 kPa. Moreover, the HA hydrogel shows prolonged stability in physiological conditions, and a stable swelling ratio is achieved within 2 h and maintained for at least 20 days. Overall, our cost-effective fabrication strategy, which integrates polysaccharide-based hydrogels and biodegradable polymer microfilms, offers a promising platform for advancing nerve tissue engineering.