An Engineered Living Intestinal Muscle Patch Produces Macroscopic Contractions that can Mix and Break Down Artificial Intestinal Contents

• Published in: Advanced materials (Weinheim) Vol. 35; no. 15; pp. e2207255 - n/a
• Main Authors: Wang, Qianqian, Wang, Jiafang, Tokhtaeva, Elmira, Li, Zhen, Martín, Martín G., Ling, Xuefeng B., Dunn, James C. Y.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.04.2023
• Subjects: Biological Factors; Biomedical materials; Gastrointestinal Contents; Gelatin; Gene expression; Humans; intestinal smooth muscle regeneration; intestinal tissue engineering; Intestines; living building blocks; Materials science; Motility; Muscle Contraction; Muscle, Smooth - physiology; Muscles; Scaffolds; Tissue Engineering; living building blocks; intestinal smooth muscle regeneration; intestinal tissue engineering
• ISSN: 0935-9648; 1521-4095
• DOI: 10.1002/adma.202207255

The intestinal muscle layers execute various gut wall movements to achieve controlled propulsion and mixing of intestinal content. Engineering intestinal muscle layers with complex contractile function is critical for developing bioartificial intestinal tissue to treat patients with short bowel syndrome. Here, the first demonstration of a living intestinal muscle patch capable of generating three distinct motility patterns and displaying multiple digesta manipulations is reported. Assessment of contractility, cellular morphology, and transcriptome profile reveals that successful generation of the contracting muscle patch relies on both biological factors in a serum‐free medium and environmental cues from an elastic electrospun gelatin scaffold. By comparing gene‐expression patterns among samples, it is shown that biological factors from the medium strongly affect ion‐transport activities, while the scaffold unexpectedly regulates cell–cell communication. Analysis of ligandreceptor interactome identifies scaffold‐driven changes in intercellular communication, and 78% of the upregulated ligand–receptor interactions are involved in the development and function of enteric neurons. The discoveries highlight the importance of combining biomolecular and biomaterial approaches for tissue engineering. The living intestinal muscle patch represents a pivotal advancement for building functional replacement intestinal tissue. It offers a more physiological model for studying GI motility and for preclinical drug discovery. An engineered intestinal muscle patch is created in vitro to generate three distinct contraction modes. It shows record strength of contractility, strong enough to mix and physically triturate viscoelastic gels that mimic the mechanical properties of the intestinal digesta. Generating such muscle patches depends on both biochemical signals from the medium and environmental cues from a bioscaffold.