Field Emily H, Ratcliffe Julian, Johnson Chad J, Binger Katrina J, Reynolds Nicholas P
Department of Biochemistry and Chemistry, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, Victoria 3086, Australia.
La Trobe University Bioimaging platform, La Trobe University, Australia, Melbourne, Victoria 3086, Australia.
Biomater Adv. 2025 Apr;169:214145. doi: 10.1016/j.bioadv.2024.214145. Epub 2024 Dec 8.
There is a pressing need for new cell-laden, printable, biomaterials that are rigid and highly biocompatible. These materials can mimic stiffer tissues such as cartilage, fibrotic tissue and cancer microenvironments, and thus have exciting applications in regenerative medicine, wound healing and cancer research. Self-assembled peptides (SAPs) functionalised with aromatic groups such as Fluorenyl-9-methoxycarbonyl (Fmoc) show promise as components of these biomaterials. However, the harsh basic conditions often used to solubilise SAPs leads to issues with toxicity and reproducibility. Here, we have designed a hybrid material comprised of self-assembled Fmoc-diphenylalanine (Fmoc-FF) assemblies dispersed throughout a sodium alginate matrix and investigated the influence of different organic solvents as peptide solubilising agents. Bioinks fabricated from peptides dissolved in 1,1,1,3,3,3-Hexafluoro-2-propanol (HFIP) showed improved biocompatibility compared to those made from Dimethyl Sulfoxide (DMSO) peptide stocks, due to the increased volatility and reduced surface tension of HFIP, allowing for more efficient expulsion from the system. Through optimisation of assembly and solvent conditions we can generate hybrid bioinks with stiffnesses up to 8 times greater than sodium alginate alone that remain highly printable, even when laden with high concentrations of cells. In addition, the shear-thinning nature of the self-assembled peptide assemblies gave the hybrid bioinks highly desirable self-healing capabilities. Our developed hybrid materials allow the bioprinting of materials previously considered too stiff to extrude without causing shear induced cytotoxicity with applications in tissue engineering and biosensing.
迫切需要新型的、可打印的、负载细胞的生物材料，这些材料要具有刚性且高度生物相容性。这些材料可以模拟更硬的组织，如软骨、纤维化组织和癌症微环境，因此在再生医学、伤口愈合和癌症研究中具有令人兴奋的应用前景。用芴基-9-甲氧基羰基（Fmoc）等芳香基团功能化的自组装肽（SAPs）有望成为这些生物材料的组成部分。然而，常用于溶解SAPs的苛刻碱性条件会导致毒性和可重复性问题。在这里，我们设计了一种混合材料，它由分散在海藻酸钠基质中的自组装芴基-二苯基丙氨酸（Fmoc-FF）组装体组成，并研究了不同有机溶剂作为肽溶解剂的影响。与由二甲基亚砜（DMSO）肽储备液制成的生物墨水相比，由溶解在1,1,1,3,3,3-六氟-2-丙醇（HFIP）中的肽制成的生物墨水显示出更好的生物相容性，这是由于HFIP的挥发性增加和表面张力降低，使得其能更有效地从系统中排出。通过优化组装和溶剂条件，我们可以生成刚度比单独的海藻酸钠高8倍的混合生物墨水，即使负载高浓度细胞时仍具有高度可打印性。此外，自组装肽组装体的剪切变稀特性赋予了混合生物墨水非常理想的自愈能力。我们开发的混合材料允许对以前认为太硬而无法挤出的材料进行生物打印，而不会引起剪切诱导的细胞毒性，可应用于组织工程和生物传感。
