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用于按需细胞封装与释放的可逆光响应蛋白水凝胶

Reversible light-responsive protein hydrogel for on-demand cell encapsulation and release.

作者信息

Narayan Om Prakash, Dong Jiawei, Huang Miao, Chen Liqiang, Liu Lu, Nguyen Vivian, Dozic Abdul Vehab, Liu Xiangping, Wang Huiliang, Yin Qian, Tang Xin, Guan Juan

机构信息

Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, University of Texas at Austin, Austin, TX 78712, USA.

Department of Mechanical and Aerospace Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL 32611, USA; University of Florida Health Cancer Center, University of Florida, Gainesville, FL 32610, USA.

出版信息

Acta Biomater. 2025 Jan 24;193:202-214. doi: 10.1016/j.actbio.2025.01.012. Epub 2025 Jan 10.

Abstract

The design of biomaterials that can reconfigure on-demand in response to external stimuli is an emerging area in materials research. However, achieving reversible assembly of protein-based biomaterials by light input remains a major challenge. Here, we present the engineering of a new protein material that is capable of switching between liquid and solid state reversibly, controlled by lights of different wavelengths. The materials are created by incorporating a light-responsive mutant Dronpa protein domain into the backbone of Elastin-Like Proteins (termed DELPs). We show that the DELP material can respond to light and undergo multiple cycles of switching between hydrogel and solution, outperforming the conventional irreversible materials. Additionally, the material is biocompatible with long-term cell proliferation in both adherent and suspension cells. Building on the reversible assembly of the material, we demonstrate efficient cell encapsulation and release upon light triggers. The design principle of incorporating a light-responsive protein element into a structural protein matrix, as demonstrated in this work enables, a broad range of other applications that require adaptive materials to intelligently interface with dynamic biological systems and environments. STATEMENT OF SIGNIFICANCE: This work generates a new class of "smart" biomaterials that uniquely switches between liquid and gel states in response to light input. Light input can be precisely delivered in space and time, highly tunable through wavelengths, intensities, and durations of light exposure. In prior research, light-responsive biomaterials are mostly irreversible, limiting their use to only uni-directional applications and the materials cannot be re-used. In contrast, this material robustly displays reversible switching between liquid and gel using a light-responsive crosslinker. Furthermore, the material is biocompatible, programmable, and suitable for broad applications including but not limited to cell encapsulation, controlled release, tissue engineering, and cell/tissue mechanobiology.

摘要

能够根据外部刺激按需重新配置的生物材料设计是材料研究中的一个新兴领域。然而,通过光输入实现基于蛋白质的生物材料的可逆组装仍然是一个重大挑战。在此,我们展示了一种新型蛋白质材料的工程设计,该材料能够在不同波长光的控制下在液态和固态之间可逆切换。这些材料是通过将光响应突变体Dronpa蛋白结构域整合到类弹性蛋白(称为DELP)的主链中而创建的。我们表明,DELP材料能够对光做出响应,并在水凝胶和溶液之间进行多次切换循环,性能优于传统的不可逆材料。此外,该材料与贴壁细胞和悬浮细胞中的长期细胞增殖具有生物相容性。基于该材料的可逆组装,我们展示了光触发下高效的细胞封装和释放。如本工作所示,将光响应蛋白元件整合到结构蛋白基质中的设计原则能够实现广泛的其他应用,这些应用需要适应性材料与动态生物系统和环境进行智能交互。重要性声明:本工作产生了一类新型的“智能”生物材料,其能够响应光输入在液体和凝胶状态之间独特地切换。光输入可以在空间和时间上精确传递,通过光的波长、强度和照射持续时间进行高度调节。在先前的研究中,光响应生物材料大多是不可逆的,限制了它们仅用于单向应用,且材料不能重复使用。相比之下,这种材料使用光响应交联剂稳健地展示了液体和凝胶之间的可逆切换。此外,该材料具有生物相容性、可编程性,适用于广泛的应用,包括但不限于细胞封装、控释、组织工程以及细胞/组织机械生物学。

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