Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022, P. R. China.
School of Applied Chemistry and Engineering, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026, P. R. China.
ACS Biomater Sci Eng. 2020 Jan 13;6(1):634-646. doi: 10.1021/acsbiomaterials.9b01601. Epub 2019 Dec 11.
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]--[dopamine methacrylamide]--[poly(ethylene glycol) methyl ether methacrylate]} [poly(ATMA--DOPAMA--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.
导电聚合物作为智能生物活性材料，在调节细胞行为和骨组织再生方面受到广泛关注。此外，传统植入物与天然骨组织之间较差的附着力可能导致移位、局部炎症和不必要的二次手术。因此，具有强附着力的导电生物粘合剂为实现粉碎性骨折的固定和再生提供了一种有效的方法。受贻贝化学启发，我们设计了导电共聚物 poly{[苯胺四聚体甲基丙烯酰胺]-[多巴胺甲基丙烯酰胺]-[聚（乙二醇）甲基醚甲基丙烯酸酯]} [poly(ATMA--DOPAMA--PEGMA); AT: 导电苯胺四聚体; DOPA: 多巴胺; PEG: 聚（乙二醇）]，其中 AT 含量分别为 3.0、6.0 和 9.0 mol%。由于氢键、π-π 相互作用和聚合物长链缠结的协同效应，共聚物的拉伸过程中的粘附强度增强，达到 1.28 MPa，其中 AT 含量为 6 mol%。前成骨细胞的生物学特性表明，生物粘合剂具有良好的生物相容性。此外，导电基底和 100 Hz、50%占空比和 500 mV 方波电刺激协同增强了成骨分化，表现为碱性磷酸酶（ALP）活性、钙沉积和成骨基因表达增加。在电刺激下，9 mol% AT 组在第 14 天的 ALP 活性和第 28 天的钙沉积明显高于 PLGA。在电刺激下，9 mol% AT 组的 OPN 表达值在第 7 天比 PLGA 显著上调 5.9 倍。总之，具有强附着力的导电聚合物与电刺激相结合可以协同上调细胞活性，有望成为骨科和牙科应用的有前途的生物粘合剂。
