A honeybee stinger-inspired self-interlocking microneedle patch and its application in myocardial infarction treatment

Yuwen Lu; Tanchen Ren; Hua Zhang; Qiao Jin; Liyin Shen; Mengqi Shan; Xinzhe Zhao; Qichao Chen; Haoli Dai; Lin Yao; Jieqi Xie; Di Ye; Tengxiang Lin; Xiaoqian Hong; Kaicheng Deng; Ting Shen; Jiazhen Pan; Mengyan Jia; Jun Ling; Peng Li; Yue Zhang; Huanan Wang; Lenan Zhuang; Changyou Gao; Jifu Mao; Yang Zhu

doi:10.1016/j.actbio.2022.09.015

A honeybee stinger-inspired self-interlocking microneedle patch and its application in myocardial infarction treatment

Acta Biomater. 2022 Nov:153:386-398. doi: 10.1016/j.actbio.2022.09.015. Epub 2022 Sep 15.

Authors

Yuwen Lu¹, Tanchen Ren², Hua Zhang³, Qiao Jin⁴, Liyin Shen¹, Mengqi Shan⁵, Xinzhe Zhao⁶, Qichao Chen⁶, Haoli Dai¹, Lin Yao⁷, Jieqi Xie¹, Di Ye³, Tengxiang Lin⁷, Xiaoqian Hong², Kaicheng Deng¹, Ting Shen¹, Jiazhen Pan³, Mengyan Jia³, Jun Ling¹, Peng Li⁷, Yue Zhang⁸, Huanan Wang⁹, Lenan Zhuang¹⁰, Changyou Gao¹¹, Jifu Mao¹², Yang Zhu¹³

Affiliations

¹ MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
² Department of Cardiology, Cardiovascular Key Laboratory of Zhejiang Province, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
³ College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
⁴ Institute of Genetics and Reproduction, College of Animal Sciences, Zhejiang University, Hangzhou, China.
⁵ College of Textiles, Donghua University, Shanghai 201620, China.
⁶ Shanghai Banyun Med Tech Co., Ltd., Shanghai 201203, China.
⁷ State Key Laboratory of Modern Optical Instrumentation, College of Optical Science and Engineering, Zhejiang University, Hangzhou 310027, China.
⁸ San Francisco Veterans Affairs Medical Center, CA 94121, USA.
⁹ College of Animal Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address: hnwang@zju.edu.cn.
¹⁰ Institute of Genetics and Reproduction, College of Animal Sciences, Zhejiang University, Hangzhou, China; Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
¹¹ MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China. Electronic address: cygao@zju.edu.cn.
¹² College of Textiles, Donghua University, Shanghai 201620, China. Electronic address: jifu.mao@dhu.edu.cn.
¹³ MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China; Binjiang Institute of Zhejiang University, Hangzhou 310053 China. Electronic address: zhuyang@zju.edu.cn.

PMID: 36116725
DOI: 10.1016/j.actbio.2022.09.015

Abstract

Weak tissue adhesion remains a major challenge in clinical translation of microneedle patches. Mimicking the structural features of honeybee stingers, stiff polymeric microneedles with unidirectionally backward-facing barbs were fabricated and embedded into various elastomer films to produce self-interlocking microneedle patches. The spirality of the barbing pattern was adjusted to increase interlocking efficiency. In addition, the micro-bleeding caused by microneedle puncturing adhered the porous surface of the patch substrate to the target tissue via coagulation. In the demonstrative application of myocardial infarction treatment, the bioinspired microneedle patches firmly fixed on challenging beating hearts, significantly reduced cardiac wall stress and strain in the infarct, and maintained left ventricular function and morphology. In addition, the microneedle patch was minimally invasively implanted onto beating porcine heart in 10 minutes, free of sutures and adhesives. Therefore, the honeybee stinger-inspired microneedles could provide an adaptive and convenient means to implant patches for various medical applications. STATEMENT OF SIGNIFICANCE: Adhesion between tissue and microneedle patches with smooth microneedles is usually weak. We introduce a novel barbing method of fabricating unidirectionally backward facing barbs with controllable spirality on the microneedles on microneedle patches. The microneedle patches self-interlock on mechanically dynamic beating hearts, similar to honeybee stingers. The micro-bleeding and coagulation on the porous surface provide additional adhesion force. The microneedle patches attenuate left ventricular remodeling via mechanical support and are compatible with minimally invasive implantation.

Keywords: Bioinspired materials; Microneedle patches; Minimally invasive surgeries; Myocardial infarction.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bees
Drug Delivery Systems
Microinjections
Myocardial Infarction* / therapy
Needles*
Punctures
Swine