Dhal Jharana, Ghovvati Mahsa, Baidya Avijit, Afshari Ronak, Cetrulo Curtis L, Abdi Reza, Annabi Nasim
Department of Chemical and Biomolecular Engineering University of California - Los Angeles Los Angeles California USA.
Department of Radiological Sciences David Geffen School of Medicine, University of California - Los Angeles Los Angeles California USA.
Bioeng Transl Med. 2024 May 3;9(5):e10667. doi: 10.1002/btm2.10667. eCollection 2024 Sep.
Successful nerve repair using bioadhesive hydrogels demands minimizing tissue-material interfacial mechanical mismatch to reduce immune responses and scar tissue formation. Furthermore, it is crucial to maintain the bioelectrical stimulation-mediated cell-signaling mechanism to overcome communication barriers within injured nerve tissues. Therefore, engineering bioadhesives for neural tissue regeneration necessitates the integration of electroconductive properties with tissue-like biomechanics. In this study, we propose a stretchable bioadhesive based on a custom-designed chemically modified elastin-like polypeptides (ELPs) and a choline-based bioionic liquid (Bio-IL), providing an electroconductive microenvironment to reconnect damaged nerve tissue. The stretchability akin to native neural tissue was achieved by incorporating hydrophobic ELP pockets, and a robust tissue adhesion was obtained due to multi-mode tissue-material interactions through covalent and noncovalent bonding at the tissue interface. Adhesion tests revealed adhesive strength ~10 times higher than commercially available tissue adhesive, Evicel®. Furthermore, the engineered hydrogel supported in vitro viability and proliferation of human glial cells. We also evaluated the biodegradability and biocompatibility of the engineered bioadhesive in vivo using a rat subcutaneous implantation model, which demonstrated facile tissue infiltration and minimal immune response. The outlined functionalities empower the engineered elastic and electroconductive adhesive hydrogel to effectively enable sutureless surgical sealing of neural injuries and promote tissue regeneration.
使用生物粘附水凝胶成功修复神经需要尽量减少组织与材料之间的界面机械不匹配，以减少免疫反应和疤痕组织形成。此外，维持生物电刺激介导的细胞信号传导机制对于克服受损神经组织内的通讯障碍至关重要。因此，设计用于神经组织再生的生物粘合剂需要将导电特性与类似组织的生物力学相结合。在本研究中，我们提出了一种基于定制设计的化学修饰弹性蛋白样多肽（ELP）和胆碱基生物离子液体（Bio-IL）的可拉伸生物粘合剂，为重新连接受损神经组织提供导电微环境。通过引入疏水性ELP口袋实现了与天然神经组织相似的拉伸性，并且由于在组织界面通过共价键和非共价键的多模式组织-材料相互作用而获得了强大的组织粘附力。粘附测试显示，其粘附强度比市售组织粘合剂Evicel®高约10倍。此外，工程化水凝胶支持人神经胶质细胞的体外活力和增殖。我们还使用大鼠皮下植入模型在体内评估了工程化生物粘合剂的生物降解性和生物相容性，结果表明其易于组织浸润且免疫反应最小。所概述的功能使工程化的弹性导电粘合剂水凝胶能够有效地实现神经损伤的无缝手术密封并促进组织再生。
