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Electroactive Dual-Drug Hydrogel-PLA Conduit for Nerve Regeneration
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DOI：10.1002/jbm.b.70066.png)
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Abstract
En 中文
Peripheral nerve injury (PNI) remains a major clinical challenge due to the limitations of autologous nerve grafting. Herein, a multifunctional composite nerve conduit was developed by integrating an oriented collagen-grafted polylactic acid (PLA) electrospun scaffold with a conductive and anti-inflammatory hydrogel to enhance peripheral nerve regeneration. The hydrogel was fabricated by chemically cross-linking carboxymethyl chitosan (CMCS) and sodium carboxymethyl cellulose (CMC-Na), incorporating polyaniline (PANI) to impart electrical conductivity and loading rhein (RH) for sustained anti-inflammatory release. The PLA conduit was further modified with collagen and loaded with nerve growth factor (NGF), forming a structurally guided dual-drug delivery system. The modified conduit exhibited improved hydrophilicity (water contact angle reduced from 107.7 degrees to 68.9 degrees) and enhanced mechanical properties (Young's modulus of 9.88 MPa). Sustained NGF and RH release reached 81.53% and 76.37% within 30 days, respectively, with stable degradation over 72 days. The conductive hydrogel displayed a uniform porous structure with high porosity (> 70%) and an electrical conductivity of 12.19 mS/cm. The electrical conductivity of the composite nerve conduit is 3.27 mS/cm. In vitro experiments demonstrated enhanced Schwann cell adhesion, neurite outgrowth, neuronal differentiation, anti-inflammatory activity, and responsiveness to electrical stimulation. In vivo studies using a rat sciatic nerve defect model confirmed significantly accelerated nerve regeneration. Overall, this electrically responsive, dual-drug-loaded hydrogel-filled nerve conduit represents a promising alternative to autologous nerve grafts for peripheral nerve repair.
Keywords:
hydrogel
nerve regeneration
peripheral nerve injury
polylactic acid
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