Multifunctional injectable hydrogels with self-healing and electroconductive properties as a potential platform for neural tissue engineering: Integration of polypyrrole and IKVAV peptide into modified alginate-hyaluronic acid networks

Injectable biomaterials have emerged as a promising option for minimally invasive tissue repair, especially in cases with small and irregular lesions. In combination with electroconductivity and self-healing abilities, these materials provide unique benefits for neural tissue engineering. They promote adaptive defect filling, assist in post-injection structural repair, and improve bioelectrical signaling. The current study focuses on the synthesis and characterization of injectable, self-healing, electroconducting hydrogels, which are intended to serve as a potential platform for addressing small and irregular neural defects. Dynamic covalent hydrazone coupling between oxidized methacrylate sodium alginate-polypyrrole (OMA-PPy) and adipic acid dihydrazide-functionalized hyaluronic acid (HA-ADH) was employed to produce hydrogels. The hydrogels were subsequently reinforced with additional photopolymerization to ensure post-injection stability. Additionally, a laminin-derived peptide called IKVAV was covalently linked to generate biomimetic signals for enhancing neuronal cell adherence and differentiation. The hydrogels demonstrated adjustable mechanical properties (elastic modulus: 72.91 ± 10.84–103.94 ± 17.72 Pa; and compressive strength: 76.87 ± 25.06–153.60 ± 37.89 kPa) and pore size (44.86 ± 23.18–76.34 ± 59.28 μm), exceptional shear thinning behavior, and self-healing abilities (recovery up to 90.35% after six cycles), along with adequate electroconductive performance suitable for minimally invasive procedures and in-situ regeneration for neural applications. In vitro studies have shown that IKVAV-functionalized hydrogels enhance the adhesion, proliferation, and differentiation of neural stem cells (NSCs) with Tuj1 expression of 6.79 ± 0.71 in the OMA-PPy/HA-ADH/IKVAV group. In addition, the OMA-PPy/HA-ADH/IKVAV formulation demonstrated favorable biocompatibility in vivo (ISO 10993-6 reactivity score: 1.22), along with a well-regulated biodegradation profile (91.6% degradation by day 21), when tested in subcutaneous implantation models. The findings indicate that optimizing a single material characteristic is insufficient; achieving a balance among bioactive signaling, secondary network connections, and dynamic covalent bonding is essential for identifying an ideal candidate material. This versatile hydrogel platform offers an encouraging approach for future research focusing on the repair and regeneration of nerve tissues, particularly in addressing localized and small-sized nerve injuries.