Mussel-Inspired Conducting Copolymer with Aniline Tetramer as Intelligent Biological Adhesive for Bone Tissue Engineering

Electrically conducting polymers have been emerging as intelligent bioactive materials for regulating cell behaviors and bone tissue regeneration. Additionally, poor adhesion between conventional implants and native bone tissue may lead to displacement, local inflammation, and unnecessary secondary surgery. Thus, a conductive bioadhesive with strong adhesion performance provides an effective approach to fulfill fixation and regeneration of comminuted bone fracture. Inspired by mussel chemistry, we designed the conductive copolymers poly{[aniline tetramer methacrylamide]-co-[dopamine methacrylamide]-co-[poly(ethylene glycol) methyl ether methacrylate]} [poly(ATMA-co-DOPAMA-co-PEGMA); AT:conductive aniline tetramer; DOPA:dopamine; PEG:poly(ethylene glycol))] with AT content 3.0, 6.0, and 9.0 mol %, respectively. The adhesive strength of this copolymer was enhanced during tensile process perhaps due to the synergistic effects of H-bonding, π-π interactions, and polymer long-chain entanglement, reaching up to 1.28 MPa with 6 mol % AT. Biological characterizations of preosteoblasts indicated that the bioadhesives exhibited desirable biocompatibility. In addition, the osteogenic differentiation was synergistically enhanced by the conductive substrate and electrical stimulation with a square wave, frequency of 100 Hz, 50% duty cycle, and electrical potential of 500 mV, as indicated by ALP activity, calcium deposition, and expression of osteogenic genes. The ALP activity at 14 days and calcium deposition at 28 days on the 9 mol % AT group were significantly higher than that on PLGA under electrical stimulation. The expression value of OPN for 9 mol % AT group was notably upregulated by 5.9-fold compared with PLGA at 7 days under electrical stimulation. Overall, the conductive polymers with strong adhesion can synergistically upregulate the cellular activity combining with electrical stimulation and might be a promising bioadhesive for orthopedic and dental applications.