Poly(Glutamic Acid‐Lysine) Hydrogels with Alternating Sequence Resist the Foreign Body Response in Rodents and Non‐Human Primates

Author:

Zhou Xianchi1ORCID,Cao Wenzhong1,Chen Yongcheng1,Zhu Zihao1,Chen Yifeng1,Ni Yanwen1,Liu Zuolong1,Jia Fan2,Lu Zhouyu3,Ye Yang3,Han Haijie3,Yao Ke3,Liu Weifeng4,Wei Xinyue5,Chen Shengfu5,Wang Youxiang1,Ji Jian167,Zhang Peng167ORCID

Affiliation:

1. MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education Department of Polymer Science and Engineering Zhejiang University Hangzhou Zhejiang 310058 P. R. China

2. Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province Department of Cardiology Sir Run Run Shaw Hospital School of Medicine Zhejiang University Hangzhou Zhejiang 310016 P. R. China

3. Eye Center The Second Affiliated Hospital School of Medicine Zhejiang Provincial Key Laboratory of Ophthalmology Zhejiang Provincial Clinical Research Center for Eye Diseases Zhejiang Provincial Engineering Institute on Eye Diseases Zhejiang University Hangzhou Zhejiang 310009 P. R. China

4. Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated Hospital School of Medicine Zhejiang University Hangzhou Zhejiang 310009 P. R. China

5. Key Laboratory of Biomass Chemical Engineering of Ministry of Education Department of Chemical and Biological Engineering Zhejiang University Hangzhou Zhejiang 310058 P. R. China

6. International Research Center for X Polymers International Campus Zhejiang University Haining Zhejiang 314400 P. R. China

7. State Key Laboratory of Transvascular Implantation Devices Zhejiang University Hangzhou Zhejiang 311202 P. R. China

Abstract

AbstractThe foreign body response (FBR) to implanted biomaterials and biomedical devices can severely impede their functionality and even lead to failure. The discovery of effective anti‐FBR materials remains a formidable challenge. Inspire by the enrichment of glutamic acid (E) and lysine (K) residues on human protein surfaces, a class of zwitterionic polypeptide (ZIP) hydrogels with alternating E and K sequences to mitigate the FBR is prepared. When subcutaneously implanted, the ZIP hydrogels caused minimal inflammation after 2 weeks and no obvious collagen capsulation after 6 months in mice. Importantly, these hydrogels effectively resisted the FBR in non‐human primate models for at least 2 months. In addition, the enzymatic degradability of the gel can be controlled by adjusting the crosslinking degree or the optical isomerism of amino acid monomers. The long‐term FBR resistance and controlled degradability of ZIP hydrogels open up new possibilities for a broad range of biomedical applications.

Funder

National Natural Science Foundation of China

National Key Research and Development Program of China

Fundamental Research Funds for the Central Universities

Publisher

Wiley

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