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PhoCoil:一种可光降解的可注射单组分重组蛋白水凝胶,用于微创递送和降解。

PhoCoil: A photodegradable and injectable single-component recombinant protein hydrogel for minimally invasive delivery and degradation.

作者信息

Gregorio Nicole E, Zhang Fan, Suita Yusuke, Ang Lisa S, Prado Olivia, Fasuyi Arafat, Olson James M, Stevens Kelly R, DeForest Cole A

机构信息

Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.

Seattle Children's Research Institute, Seattle, WA 98101, USA.

出版信息

Sci Adv. 2025 Aug 29;11(35):eadx3472. doi: 10.1126/sciadv.adx3472. Epub 2025 Aug 27.

DOI:10.1126/sciadv.adx3472
PMID:40864698
Abstract

Hydrogel biomaterials offer great promise for three-dimensional cell culture and therapeutic delivery. Despite many successes, challenges persist in that gels formed from natural proteins are only marginally tunable whereas those derived from synthetic polymers lack intrinsic bioinstructivity. Toward the creation of biomaterials with both excellent biocompatibility and customizability, recombinant protein-based hydrogels have emerged as molecularly defined and user-programmable platforms that mimic the proteinaceous nature of the extracellular matrix. Here, we introduce PhoCoil, a dynamically tunable recombinant hydrogel formed from a single protein component with unique multistimuli responsiveness. Physical cross-linking through coiled-coil interactions promotes rapid shear-thinning and self-healing behavior, rendering the gel injectable, whereas an included photodegradable motif affords on-demand network dissolution via visible light. PhoCoil gel photodegradation can be spatiotemporally and lithographically controlled in a dose-dependent manner, through complex tissue, and without harm to encapsulated cells. We anticipate that PhoCoil will further enable applications in tissue engineering and regenerative medicine.

摘要

水凝胶生物材料在三维细胞培养和治疗递送方面展现出巨大潜力。尽管已取得诸多成功,但仍存在挑战,天然蛋白质形成的凝胶仅有有限的可调性,而合成聚合物衍生的凝胶缺乏内在的生物指导性。为了创建具有优异生物相容性和可定制性的生物材料,基于重组蛋白的水凝胶已成为分子定义明确且用户可编程的平台,可模拟细胞外基质的蛋白质性质。在此,我们介绍PhoCoil,一种由单一蛋白质组分形成的动态可调重组水凝胶,具有独特的多刺激响应性。通过卷曲螺旋相互作用进行的物理交联促进了快速剪切变稀和自愈行为,使凝胶可注射,而包含的光可降解基序可通过可见光实现按需网络溶解。PhoCoil凝胶的光降解可以通过复杂组织以剂量依赖的方式进行时空和光刻控制,且不会对封装的细胞造成伤害。我们预计PhoCoil将进一步推动其在组织工程和再生医学中的应用。

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本文引用的文献

1
The Photocleavable Protein PhoCl-Based Dynamic Hydrogels.基于光可裂解蛋白PhoCl的动态水凝胶。
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Coiled-Coil Protein Hydrogels Engineered with Minimized Fiber Diameters for Sustained Release of Doxorubicin in Triple-Negative Breast Cancer.采用最小纤维直径设计的卷曲螺旋蛋白水凝胶用于三阴性乳腺癌中多柔比星的持续释放。
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Design of Coiled-Coil Protein Nanostructures for Therapeutics and Drug Delivery.
用于治疗和药物递送的卷曲螺旋蛋白纳米结构设计
Annu Rev Chem Biomol Eng. 2024 Apr 10. doi: 10.1146/annurev-chembioeng-100722-122348.
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Engineering Antigen-Specific Tolerance to an Artificial Protein Hydrogel.工程化抗原特异性耐受人工蛋白水凝胶。
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Genetically Encoded XTEN-based Hydrogels with Tunable Viscoelasticity and Biodegradability for Injectable Cell Therapies.基于 XTEN 的基因编码水凝胶具有可调粘弹性和生物可降解性,可用于可注射细胞治疗。
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A Library of Elastin-like Proteins with Tunable Matrix Ligands for 3D Neural Cell Culture.用于3D神经细胞培养的具有可调节基质配体的类弹性蛋白文库。
Biomacromolecules. 2023 Dec 11;24(12):5926-5939. doi: 10.1021/acs.biomac.3c00941. Epub 2023 Nov 21.
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Recombinant protein-based injectable materials for biomedical applications.用于生物医学应用的基于重组蛋白的可注射材料。
Adv Drug Deliv Rev. 2023 Feb;193:114673. doi: 10.1016/j.addr.2022.114673. Epub 2022 Dec 24.
10
100th Anniversary of Macromolecular Science Viewpoint: Synthetic Protein Hydrogels.大分子科学观点100周年:合成蛋白质水凝胶
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