自组装多肽水凝胶的制备、设计、性能及应用研究进展
Progress in the Design, Preparation, Performance and Application of Self-Assembling Peptide Hydrogels
DOI: 10.12677/amc.2026.142020, PDF,    科研立项经费支持
作者: 顾小明, 赵东欣*：河南工业大学化学化工学院，河南 郑州
关键词: 自组装多肽；水凝胶；设计制备；生物相容性；生物医学应用；Self-Assembling Peptide； Hydrogel； Design and Preparation； Biocompatibility； Biomedical Application
摘要: 自组装多肽水凝胶是一类由氨基酸通过酰胺键连接构成的功能性超分子材料，具有纯度高、无免疫原性、降解产物无毒、生物相容性优良等特点。其形成过程中，多肽分子通过分子内与分子间的非共价相互作用，发生分级组装，构建出与细胞外基质结构相似的三维网络，因而在生物医学领域具有独特而重要的应用价值。本文梳理了自组装多肽水凝胶的制备方法、分子设计要素与关键性能，阐述了该类材料在抗癌治疗、药物递送、抗菌与伤口愈合、组织工程等方面的代表性应用及其作用机制，展望了其未来可能的发展，期望可以为自组装多肽水凝胶的深入研究与实际应用提供系统而全面的参考。
Abstract: Selft-assembling peptide hydrogel is a class of functional supramolecular materials formed by amino acids linked via amide bonds, which has the characteristics of high purity, no immunogenicity, non-toxic degradation products, and excellent biocompatibility. During its formation, peptide molecules undergo hierarchical assembly through intramolecular and intermolecular noncovalent interactions, constructing a three-dimensional network similar in structure to the extracellular matrix. Therefore, it has unique and important application value in the biomedical field. In this paper, the preparation methods, molecular design elements and key properties of self-assembled peptide hydrogels were reviewed. The representative applications and mechanisms of these materials in anti-cancer treatment, drug delivery, antibacterial and wound healing, tissue engineering and other aspects were described. The possible development direction of self-assembling peptide hydrogels was prospected, with the aim of providing a systematic and comprehensive reference for the in-depth study and practical application of self-assembled peptide hydrogels.
文章引用：顾小明, 赵东欣. 自组装多肽水凝胶的制备、设计、性能及应用研究进展[J]. 材料化学前沿, 2026, 14(2): 187-199. https://doi.org/10.12677/amc.2026.142020

参考文献

[1] Whitesides, G.M. and Grzybowski, B. (2002) Self-Assembly at All Scales. Science, 295, 2418-2421. [Google Scholar] [CrossRef] [PubMed]
[2] Guo, W., Ma, Y., Hu, L., Feng, Y., Liu, Y., Yi, X., et al. (2022) Modification Strategies for Ionic Complementary Self-Assembling Peptides: Taking RADA16-I as an Example. Polymers, 14, Article 5221. [Google Scholar] [CrossRef] [PubMed]
[3] Song, Q., Cheng, Z., Kariuki, M., Hall, S.C.L., Hill, S.K., Rho, J.Y., et al. (2021) Molecular Self-Assembly and Supramolecular Chemistry of Cyclic Peptides. Chemical Reviews, 121, 13936-13995. [Google Scholar] [CrossRef] [PubMed]
[4] Adak, A., Das, G., Barman, S., Mohapatra, S., Bhunia, D., Jana, B., et al. (2017) Biodegradable Neuro-Compatible Peptide Hydrogel Promotes Neurite Outgrowth, Shows Significant Neuroprotection, and Delivers Anti-Alzheimer Drug. ACS Applied Materials & Interfaces, 9, 5067-5076. [Google Scholar] [CrossRef] [PubMed]
[5] Zhang, Z., Gao, J., Yuan, L., Duan, B., Yang, H., Ma, L., et al. (2025) Self-Assembling Peptide Hydrogels: Design, Mechanisms, Characterization, and Biomedical Applications. Soft Matter, 21, 4771-4791. [Google Scholar] [CrossRef] [PubMed]
[6] Fu, K., Wu, H. and Su, Z. (2021) Self-Assembling Peptide-Based Hydrogels: Fabrication, Properties, and Applications. Biotechnology Advances, 49, Article ID: 107752. [Google Scholar] [CrossRef] [PubMed]
[7] Khine, Y.Y., Nguyen, H., Afolabi, F. and Lin, C. (2024) Fast-Relaxing Hydrogels with Reversibly Tunable Mechanics for Dynamic Cancer Cell Culture. Biomaterials Advances, 159, Article ID: 213829. [Google Scholar] [CrossRef] [PubMed]
[8] Frayssinet, A., Petta, D., Illoul, C., Haye, B., Markitantova, A., Eglin, D., et al. (2020) Extracellular Matrix-Mimetic Composite Hydrogels of Cross-Linked Hyaluronan and Fibrillar Collagen with Tunable Properties and Ultrastructure. Carbohydrate Polymers, 236, Article ID: 116042. [Google Scholar] [CrossRef] [PubMed]
[9] Pogostin, B.H., Wu, S.X., Swierczynski, M.J., Pennington, C., Li, S., Vohidova, D., et al. (2025) Nanofibrous Supramolecular Peptide Hydrogels for Controlled Release of Small-Molecule Drugs and Biologics. Nature Nanotechnology, 20, 1502-1513. [Google Scholar] [CrossRef] 
[10] Dong, Y., A, S., Rodrigues, M., Li, X., Kwon, S.H., Kosaric, N., et al. (2017) Injectable and Tunable Gelatin Hydrogels Enhance Stem Cell Retention and Improve Cutaneous Wound Healing. Advanced Functional Materials, 27, Article ID: 1606619. [Google Scholar] [CrossRef] 
[11] Wei, D., Dong, H., Huang, W., Xie, W., Chen, S., Zhang, G., et al. (2026) Microcrystalline‐Infused Peptide Hydrogel Enables Sustained Tacrolimus Delivery to Prolong Survival and Prevent Rejection in Kidney Transplantation. Advanced Materials, 38, e72590. [Google Scholar] [CrossRef] 
[12] Najafi, H., Jafari, M., Farahavar, G., Abolmaali, S.S., Azarpira, N., Borandeh, S., et al. (2021) Recent Advances in Design and Applications of Biomimetic Self-Assembled Peptide Hydrogels for Hard Tissue Regeneration. Bio-Design and Manufacturing, 4, 735-756. [Google Scholar] [CrossRef] [PubMed]
[13] Zhang, J., Zou, J. and Ren, J. (2025) Recent Advances in Glycopeptide Hydrogels: Design, Biological Functions, and Biomedical Applications. Frontiers in Bioengineering and Biotechnology, 13, Article 1577192. [Google Scholar] [CrossRef] [PubMed]
[14] Wang, X., Meng, R., Zhang, H. and Li, W. (2025) Colloidal Supramolecular Cross-Linkers: A Versatile Platform for Physical Condensation of Oligopeptide Segments into All-Underwater Adhesives. Nano Letters, 25, 10528-10535. [Google Scholar] [CrossRef] [PubMed]
[15] Karavasili, C. and Fatouros, D.G. (2021) Self-assembling Peptides as Vectors for Local Drug Delivery and Tissue Engineering Applications. Advanced Drug Delivery Reviews, 174, 387-405. [Google Scholar] [CrossRef] [PubMed]
[16] Wang, R., Wang, Z., Guo, Y., Li, H. and Chen, Z. (2019) Design of a RADA16-Based Self-Assembling Peptide Nanofiber Scaffold for Biomedical Applications. Journal of Biomaterials Science, Polymer Edition, 30, 713-736. [Google Scholar] [CrossRef] [PubMed]
[17] Yang, Z., Wang, Y. and Zhu, H. (2025) Emerging Self-Assembled Peptide Hydrogels for Enhanced Wound Healing. Nanomedicine, 20, 2217-2236. [Google Scholar] [CrossRef] [PubMed]
[18] Yu, D., Han, N., Son, H., Kim, S.J. and Kweon, S. (2026) Functional Peptide-Based Biomaterials for Pharmaceutical Application: Sequences, Mechanisms, and Optimization Strategies. Journal of Functional Biomaterials, 17, Article 37. [Google Scholar] [CrossRef] 
[19] Dong, S., Han, Y., Wang, Y., Ding, Q., Ding, C., Chen, S., et al. (2025) Multifunctional Hydrogel Scaffolds Loaded with Peptides in Promoting Wound Healing: A Review. International Journal of Biological Macromolecules, 330, Article ID: 148128. [Google Scholar] [CrossRef] 
[20] Luo, Y., Liu, X., Dong, Z. and Song, Y. (2025) Molecular-Level Design Principles and Strategies of Peptide Self-Assembly Nanomaterials: From Sequence Engineering to Functional Applications. International Journal of Nanomedicine, 20, 15277-15312. [Google Scholar] [CrossRef] 
[21] Zhou, P., Xing, R., Li, Q., Li, J., Yuan, C. and Yan, X. (2023) Steering Phase-Separated Droplets to Control Fibrillar Network Evolution of Supramolecular Peptide Hydrogels. Matter, 6, 1945-1963. [Google Scholar] [CrossRef] 
[22] Scott, D.A., Wasmuth, A., Abelardo, E., Hudson, K.L., Thomson, A.R., Birchall, M.A., et al. (2024) Modular Tunable α‐Helical Peptide Hydrogels for Neuronal Cells. Advanced Functional Materials, 35, Article ID: 2410333. [Google Scholar] [CrossRef] 
[23] Zhang, S. (2017) Discovery and Design of Self-Assembling Peptides. Interface Focus, 7, Article ID: 20170028. [Google Scholar] [CrossRef] [PubMed]
[24] Dong, H., Wang, M., Fan, S., Wu, C., Zhang, C., Wu, X., et al. (2022) Redox‐Regulated Conformational Change of Disulfide‐Rich Assembling Peptides. Angewandte Chemie International Edition, 61, e202212829. [Google Scholar] [CrossRef] [PubMed]
[25] Sırma Tarım, B., Tamburacı, S., Uysal, B. and Top, A. (2025) Integration of Leu-Asp-Val Cell Attachment Motif into Self-Assembling Peptide Sequences for Nanofibrillar Hydrogel Formation in Wound Healing. ACS Applied Nano Materials, 8, 5302-5314. [Google Scholar] [CrossRef] 
[26] Silva, D., Natalello, A., Sanii, B., Vasita, R., Saracino, G., Zuckermann, R.N., et al. (2013) Synthesis and Characterization of Designed Bmhp1-Derived Self-Assembling Peptides for Tissue Engineering Applications. Nanoscale, 5, 704-718. [Google Scholar] [CrossRef] [PubMed]
[27] Siddiqui, Z., Sarkar, B., Kim, K.K., Kumar, A., Paul, R., Mahajan, A., et al. (2021) Self-Assembling Peptide Hydrogels Facilitate Vascularization in Two-Component Scaffolds. Chemical Engineering Journal, 422, Article ID: 130145. [Google Scholar] [CrossRef] [PubMed]
[28] Das, A., Vaghela, D., Gupta, S., Bhatia, D. and Biswas, A. (2025) Self-Assembly of Short Peptides and DNA-Based Materials in Precision Biomedical Applications. Supramolecular Materials. [Google Scholar] [CrossRef] 
[29] Li, C., Zhou, X., Shao, Y., Chen, P., Xing, Y., Yang, Z., et al. (2017) A Supramolecular Hydrogel with Identical Cross-Linking Point Density but Distinctive Rheological Properties. Materials Chemistry Frontiers, 1, 654-659. [Google Scholar] [CrossRef] 
[30] Zhai, Z., Xu, K., Mei, L., Wu, C., Liu, J., Liu, Z., et al. (2019) Co-Assembled Supramolecular Hydrogels of Cell Adhesive Peptide and Alginate for Rapid Hemostasis and Efficacious Wound Healing. Soft Matter, 15, 8603-8610. [Google Scholar] [CrossRef] [PubMed]
[31] Xu, Y., Yang, X., Thomas, A.K., Patsis, P.A., Kurth, T., Kräter, M., et al. (2018) Noncovalently Assembled Electroconductive Hydrogel. ACS Applied Materials & Interfaces, 10, 14418-14425. [Google Scholar] [CrossRef] [PubMed]
[32] An, L., Wang, S., Liao, B., Liu, J., Jin, X., Cai, Y., et al. (2025) Living Organisms Growth and Release Immobilized in an Assembled Dipeptide Hydrogel. Journal of Colloid and Interface Science, 686, 462-470. [Google Scholar] [CrossRef] [PubMed]
[33] Zhang, F., Zhang, H.J., Wang, S.F., Gao, M.Y., Du, K.Y., Chen, X.Y., et al. (2025) A Dynamically Phase-Adaptive Regulating Hydrogel Promotes Ultrafast Anti-Fibrotic Wound Healing. Nature Communications, 16, Article ID: 3738. [Google Scholar] [CrossRef] [PubMed]
[34] Cao, F., Ma, G., Mei, L., Zhu, G., Song, M., Qin, Q., et al. (2021) Development of Disulfide Bond Crosslinked Antimicrobial Peptide Hydrogel. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 626, Article ID: 127026. [Google Scholar] [CrossRef] 
[35] López-Santiago, R.F., Delgado, J. and Castillo, R. (2024) Competition among Physical, Chemical, and Hybrid Gelation Mechanisms in Biopolymers. Soft Matter, 20, 2518-2531. [Google Scholar] [CrossRef] [PubMed]
[36] Taief, K.A., Nemec, S., Middleton, I.A., Kilian, K.A. and Thordarson, P. (2025) Scrambled RGD Hexameric Peptide Hydrogel Supports Efficient Self‐Assembly and Cell Activity. Chemistry—A European Journal, 31, e202404410. [Google Scholar] [CrossRef] [PubMed]
[37] Kocgozlu, L., Mutschler, A., Tallet, L., Calligaro, C., Knopf-Marques, H., Lebaudy, E., et al. (2024) Cationic Homopolypeptides: A Versatile Tool to Design Multifunctional Antimicrobial Nanocoatings. Materials Today Bio, 28, Article ID: 101168. [Google Scholar] [CrossRef] [PubMed]
[38] Agrawal, A., Euliano, E.M., Pogostin, B.H., Yu, M.H., Swain, J.W.R., Hartgerink, J.D., et al. (2024) Probing the Effects of Chirality on Self-Assembling Peptides: Hydrogel Formation, Degradation, Antigen Release, and Adjuvancy. Cellular and Molecular Bioengineering, 17, 441-451. [Google Scholar] [CrossRef] [PubMed]
[39] Ibrahim, M.I.A., Bodiguel, J., Pickaert, G., Stefan, L., Matsuo, K. and Averlant-Petit, M. (2025) Supramolecular Hydrogels Derived from 2 : 1-[α/aza]-Pseudopeptides: Design, Structural Analysis and Self-Assembly in Solution, Solid, and Gel States. Journal of Materials Chemistry B, 13, 7437-7448. [Google Scholar] [CrossRef] [PubMed]
[40] Gentile, L., Frohm, B., Malmendal, A., Åkerfeldt, K.S., Olsson, U. and Linse, S. (2025) Charge Regulation in Peptide Self-Assembly and Hydrogelation. Journal of Colloid and Interface Science, 700, Article ID: 138615. [Google Scholar] [CrossRef] [PubMed]
[41] Blanco-Gómez, A., Barravecchia, L., Scarel, E., De Zorzi, R., Colomina-Alfaro, L., Bandiera, A., et al. (2026) Dual Ph-Responsive Pseudopeptide: Hydrogelation and Self-Assembly into Single-and Multi-Walled Nanotubes. Nanoscale, 18, 3365-3376. [Google Scholar] [CrossRef] 
[42] Luo, Z., Zhao, X. and Zhang, S. (2008) Structural Dynamic of a Self-Assembling Peptide D-EAK16 Made of Only D-Amino Acids. PLOS ONE, 3, e2364. [Google Scholar] [CrossRef] [PubMed]
[43] Mohanty, S. and Roy, S. (2025) Fabricating N-Cadherin Mimetic Peptide-Based Diverse Self-Assembled Hydrogels in the Presence of Biologically Relevant Cations. Biomacromolecules, 26, 2238-2255. [Google Scholar] [CrossRef] [PubMed]
[44] Pang, Y., Zhang, W., Zhao, Y., Hao, H., Wang, H. and Liang, J. (2024) A Self-Assembling Peptide Nanofiber Hydrogel for Biomaterials with Rapid Stimulation Response to Naturally Positively Charged Group Substances. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 684, Article ID: 133118. [Google Scholar] [CrossRef] 
[45] Seyedkarimi, M., Mirzadeh, H., Mohammadi, A. and Bagheri-Khoulenjani, S. (2020) Mechanical Characteristics of SPG-178 Hydrogels: Optimizing Viscoelastic Properties through Microrheology and Response Surface Methodology. Iranian Biomedical Journal, 24, 110-118. [Google Scholar] [CrossRef] [PubMed]
[46] Larsen, T.H., Branco, M.C., Rajagopal, K., Schneider, J.P. and Furst, E.M. (2009) Sequence-Dependent Gelation Kinetics of Β-Hairpin Peptide Hydrogels. Macromolecules, 42, 8443-8450. [Google Scholar] [CrossRef] [PubMed]
[47] Xin, Y., Ligorio, C., O’brien, M., Collins, R., Dong, S., Miller, A.F., et al. (2024) Effect of Supramolecular Peptide Hydrogel Scaffold Charge on HepG2 Viability and Spheroid Formation. Journal of Materials Chemistry B, 12, 12553-12566. [Google Scholar] [CrossRef] [PubMed]
[48] Ye, G., Luo, S., Zafar, H., Ge, H., Liu, B., Wang, N., et al. (2024) pH-Sensitive Supramolecular Self-Assembled Peptide Hydrogel for the Treatment of Esophageal Cancer. Frontiers in Pharmacology, 15, Article 1453422. [Google Scholar] [CrossRef] [PubMed]
[49] Liu, Z., Yu, C., Li, Z., Wang, X., Shang, D. and Dong, W. (2025) Matrix Metalloproteinase-Triggered Self-Assembling Peptides for Biomedical Applications. Journal of Materials Chemistry B, 13, 8298-8334. [Google Scholar] [CrossRef] [PubMed]
[50] Rosenbusch, I., Mählmann, D. and Ravoo, B.J. (2025) Near-Infrared Responsive Three-Component Supramolecular Hydrogels of Peptide, Agarose and Upconversion Nanoparticles. Faraday Discussions, 260, 377-388. [Google Scholar] [CrossRef] [PubMed]
[51] Feng, T., Wu, H., Ma, W., Wang, Z., Wang, C., Wang, Y., et al. (2022) An Injectable Thermosensitive Hydrogel with a Self-Assembled Peptide Coupled with an Antimicrobial Peptide for Enhanced Wound Healing. Journal of Materials Chemistry B, 10, 6143-6157. [Google Scholar] [CrossRef] [PubMed]
[52] Yan, C., Mackay, M.E., Czymmek, K., Nagarkar, R.P., Schneider, J.P. and Pochan, D.J. (2012) Injectable Solid Peptide Hydrogel as a Cell Carrier: Effects of Shear Flow on Hydrogels and Cell Payload. Langmuir, 28, 6076-6087. [Google Scholar] [CrossRef] [PubMed]
[53] Santillán, F., Shamiya, Y., Chakraborty, A., Zahid, A.A., Veliz, L., Lagugné-Labarthet, F., et al. (2026) Cyclic Peptide-Based Shear-Thinning and Self-Healing Hydrogels as Injectable Nanotherapeutics. Biomaterials Science, 14, 1411-1417. [Google Scholar] [CrossRef] 
[54] Aleem, A.R., Ali, W., Pan, H., Xia, C., Liu, C., Yan, Z., et al. (2025) Multifunctional Peptide-and Natural Polymer-Based Smart Biomaterials: Synthetic Approaches and Cancer Treatment Applications. Coordination Chemistry Reviews, 544, Article ID: 216980. [Google Scholar] [CrossRef] 
[55] Li, J., Wang, Z., Han, H., Xu, Z., Li, S., Zhu, Y., et al. (2022) Short and Simple Peptide-Based pH-Sensitive Hydrogel for Antitumor Drug Delivery. Chinese Chemical Letters, 33, 1936-1940. [Google Scholar] [CrossRef] 
[56] Gong, M., Hua, D., Kong, W., Zheng, X., Zhou, Z., Yu, B., et al. (2014) Potent Tumor Targeting Drug Release System Comprising MMP-2 Specific Peptide Fragment with Self-Assembling Characteristics. Drug Design, Development and Therapy, 8, 1839-1849. [Google Scholar] [CrossRef] [PubMed]
[57] Leyva-Aranda, V., Singh, S., Telesforo, M.J., Young, S., Yee, C. and Hartgerink, J.D. (2024) Nanofibrous Multidomain Peptide Hydrogels Provide T Cells a 3D, Cytocompatible Environment for Cell Expansion and Antigen-Specific Killing. ACS Biomaterials Science & Engineering, 10, 1448-1460. [Google Scholar] [CrossRef] [PubMed]
[58] Heremans, J., Ballet, S. and Martin, C. (2025) The Versatility of Peptide Hydrogels: From Self‐Assembly to Drug Delivery Applications. Journal of Peptide Science, 31, e3662. [Google Scholar] [CrossRef] [PubMed]
[59] Divanach, P., Noti, A., Vouvopoulos, P., Athanasiou, T., Kountourakis, N., Harmandaris, V., et al. (2025) FmocFF Peptide Hydrogel Is a Promising Matrix for Encapsulation and Controlled Release of the Anticancer Peptide Drug Bortezomib. Biomolecules, 15, Article 839. [Google Scholar] [CrossRef] [PubMed]
[60] Eweje, F., Ibrahim, V., Shajii, A., Walsh, M.L., Ahmad, K., Alrefai, A., et al. (2025) Self-Assembling Protein Nanoparticles for Cytosolic Delivery of Nucleic Acids and Proteins. Nature Biotechnology. [Google Scholar] [CrossRef] [PubMed]
[61] Wei, X., Wang, Z., Yue, L., Xu, F. and Zhang, H. (2025) Advances in Research of Polypeptide Nanozyme Hydrogels in Promoting Wound Healing: A Review. Materials & Design, 260, Article ID: 115171. [Google Scholar] [CrossRef] 
[62] Devi, R., Singh, G., Singh, A., Singh, J., Kaur, N. and Singh, N. (2024) Silver and Copper Nanoparticle-Loaded Self-Assembled Pseudo-Peptide Thiourea-Based Organic–inorganic Hybrid Gel with Antibacterial and Superhydrophobic Properties for Antifouling Surfaces. ACS Applied Bio Materials, 7, 4162-4174. [Google Scholar] [CrossRef] [PubMed]
[63] Xie, X., Gao, C., Tan, L., Chen, L., Fan, J., Xiong, W., et al. (2025) Gene-Engineered Polypeptide Hydrogels with On-Demand Oxygenation and ECM-Cell Interaction Mimicry for Diabetic Wound Healing. Biomaterials, 316, Article ID: 122984. [Google Scholar] [CrossRef] [PubMed]
[64] Laigle, C., Buffier, M., Clémens, E., Sankar, S. and Rousselle, P. (2026) Self-Assembled Peptide RADA16 Hydrogel Supports Wound Epithelialization by a Laminin-332-Dependent Binding Mechanism. Acta Biomaterialia, 209, 194-210. [Google Scholar] [CrossRef] 
[65] Li, W., Li, L., Hu, J., Zhou, D. and Su, H. (2025) Design and Applications of Supramolecular Peptide Hydrogel as Artificial Extracellular Matrix. Biomacromolecules, 25, 6967-6986. [Google Scholar] [CrossRef] [PubMed]
[66] Ma, T., Yu, Y., Gao, Y., Jiang, S., Ge, W., Zeng, Y., et al. (2025) Smart Self-Assembled Peptide-Based Hydrogels: Mechanism, Design and Biomedical Applications. Colloids and Surfaces B: Biointerfaces, 253, Article ID: 114704. [Google Scholar] [CrossRef] [PubMed]
[67] Su, X., Yang, B., Chen, L., Liu, Q., Liu, A., Tan, M., et al. (2026) Peptide-Based Co-Assembling Materials: Bridging Fundamental Science and Versatile Applications. Progress in Materials Science, 156, Article ID: 101562. [Google Scholar] [CrossRef] 
[68] Ross, A., Guo, X., Salazar, G.A.M., Schejtman, S.D.G., El‐Hage, J., Comtois‐Bona, M., et al. (2024) Multipurpose On‐the‐Spot Peptide‐Based Hydrogels for Skin, Cornea, and Heart Repair. Advanced Functional Materials, 34, Article ID: 2402564. [Google Scholar] [CrossRef]