Sustained Release of Nitric Oxide‐Mediated Angiogenesis and Nerve Repair by Mussel‐Inspired Adaptable Microreservoirs for Brain Traumatic Injury Therapy

Author:

Liu Hsiu‐Ching1,Huang Chu‐Han1,Chiang Min‐Ren1,Hsu Ru‐Siou2,Chou Tsu‐Chin3,Lu Tsai‐Te456,Lee I‐Chi1,Liao Lun‐De7,Chiou Shih‐Hwa89,Lin Zhong‐Hong10,Hu Shang‐Hsiu1ORCID

Affiliation:

1. Department of Biomedical Engineering and Environmental Sciences National Tsing Hua University 300044 Hsinchu Taiwan

2. Department of Chemistry Stanford University Stanford CA 94305 USA

3. Institute of Analytical and Environmental Sciences National Tsing Hua University 300044 Hsinchu Taiwan

4. Institute of Biomedical Engineering National Tsing Hua University 300044 Hsinchu Taiwan

5. Department of Chemistry Chung Yuan Christian University Taoyuan 320314 Taiwan

6. Department of Chemistry National Tsing Hua University Hsinchu 300044 Taiwan

7. Institute of Biomedical Engineering and Nanomedicine National Health Research Institutes 35053 Miaoli County Taiwan

8. Department of Medical Research National Yang Ming Chiao Tung University Taipei Veterans General Hospital 112304 Taipei Taiwan

9. Institute of Pharmacology, School of Medicine National Yang Ming Chiao Tung University Taipei 112304 Taiwan

10. Department of Biomedical Engineering National Taiwan University 10617 Taipei Taiwan

Abstract

AbstractTraumatic brain injury (TBI) triggers inflammatory response and glial scarring, thus substantially hindering brain tissue repair. This process is exacerbated by the accumulation of activated immunocytes at the injury site, which contributes to scar formation and impedes tissue repair. In this study, a mussel‐inspired nitric oxide‐release microreservoir (MINOR) that combines the features of reactive oxygen species (ROS) scavengers and sustained NO release to promote angiogenesis and neurogenesis is developed for TBI therapy. The injectable MINOR fabricated using a microfluidic device exhibits excellent monodispersity and gel‐like self‐healing properties, thus allowing the maintenance of its structural integrity and functionality upon injection. Furthermore, polydopamine in the MINOR enhances cell adhesion, significantly reduces ROS levels, and suppresses inflammation. Moreover, a nitric oxide (NO) donor embedded into the MINOR enables the sustained release of NO, thus facilitating angiogenesis and mitigating inflammatory responses. By harnessing these synergistic effects, the biocompatible MINOR demonstrates remarkable efficacy in enhancing recovery in mice. These findings benefit future therapeutic interventions for patients with TBI.

Funder

National Science and Technology Council

National Tsing Hua University

National Health Research Institutes

Publisher

Wiley

Subject

Pharmaceutical Science,Biomedical Engineering,Biomaterials

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