Department of Biohybrid & Medical Textiles (BioTex), AME-Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, D-52074 Aachen, Germany.
Bioforge Lab, Group for Advanced Materials and Nanobiotechnology, Biomedical Networking Research Center of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Edificio LUCIA, Universidad de Valladolid, 47011 Valladolid, Spain.
Int J Mol Sci. 2023 Apr 5;24(7):6776. doi: 10.3390/ijms24076776.
More than 260 million surgical procedures are performed worldwide each year. Although sutures and staples are widely used to reconnect tissues, they can cause further damage and increase the risk of infection. Bioadhesives have been proposed as an alternative to reconnect tissues. However, clinical adhesives that combine strong adhesion with cytocompatibility have yet to be developed. In this study, we explored the production of adhesives based on protein-engineered polymers bioinspired by the sequence of elastin (i.e., elastin-like recombinamers, ELRs). We hypothesized that the combination of polyphenols (i.e., tannic acid, TA) and ELRs would produce an adhesive coacervate (ELR+TA), as reported for other protein polymers such as silk fibroin (SF). Notably, the adhesion of ELR alone surpassed that of ELR+TA. Indeed, ELR alone achieved adhesive strengths of 88.8 ± 33.2 kPa and 17.0 ± 2.0 kPa on porcine bone and skin tissues, respectively. This surprising result led us to explore a multicomponent bioadhesive to encompass the complementary roles of elastin (mimicked here by ELR) and silk fibroin (SF), and subsequently mirror more closely the multicomponent nature of the extracellular matrix. Tensile testing showed that ELR+SF achieved an adhesive strength of 123.3 ± 60.2 kPa on porcine bone and excellent cytocompatibility. To express this in a more visual and intuitive way, a small surface of only 2.5 cm was able to lift at least 2 kg of weight. This opens the door for further studies focusing on the ability of protein-engineered polymers to adhere to biological tissues without further chemical modification for applications in tissue engineering.
每年在全球范围内进行的手术操作超过 2.6 亿例。尽管缝线和订书钉被广泛用于重新连接组织,但它们会造成进一步的损伤,并增加感染的风险。生物粘合剂已被提议作为重新连接组织的替代方法。然而,尚未开发出具有强附着力和细胞相容性的临床用粘合剂。在这项研究中,我们探索了基于弹性蛋白序列(即弹性蛋白样重组体,ELR)设计的蛋白质工程聚合物生产粘合剂。我们假设多酚(即单宁酸,TA)和 ELR 的组合将产生一种粘合凝聚物(ELR+TA),就像其他蛋白质聚合物(如丝素蛋白,SF)一样。值得注意的是,单独的 ELR 的粘附力超过了 ELR+TA。实际上,ELR 单独在猪骨和皮肤组织上的粘附力分别达到了 88.8±33.2kPa 和 17.0±2.0kPa。这一令人惊讶的结果促使我们探索一种多组分生物粘合剂,以包含弹性蛋白(在这里由 ELR 模拟)和丝素蛋白(SF)的互补作用,从而更紧密地模拟细胞外基质的多组分性质。拉伸测试表明,ELR+SF 在猪骨上的粘附强度为 123.3±60.2kPa,具有出色的细胞相容性。为了更直观地表达这一点,仅 2.5cm2 的小表面就能够举起至少 2kg 的重量。这为进一步研究蛋白质工程聚合物在组织工程中的应用开辟了道路,这些聚合物无需进一步的化学修饰即可具有粘附生物组织的能力。