Biological Tissue-Inspired Living Self-Healing Hydrogels Based on Cadherin-Mediated Specific Cell–Cell Adhesion

Abstract

Regarding synthetic self-healing materials, as healing reactions occur at the molecular level, bond formation occurs when healing chemicals are nanometer distances apart. However, motility of healing chemicals in materials is quite limited, permitting only passive diffusion, which reduces the chance of bond formation. By contrast, biological-tissues exhibit significant high-performance self-healing, and cadherin-mediated cell−cell adhesion is a key mechanism in the healing process. This is because cells are capable of a certain level of motility and actively migrate to damage sites, thereby achieving cell−cell adhesion with high efficacy. Here, we report biological-tissue-inspired, self-healing hydrogels in which azide-modified living cells are covalently cross-linked with alkyne-modified alginate polymers via bioorthogonal reactions. As a proof-of-concept, we demonstrate their unique self-healing capabilities originating from cadherin-mediated adhesion between cells incorporated into the gels as mobile healing mechanism. This study provides an example of self-healing material incorporating living components into a synthetic material to promote self-healing.

Bio‐inspired adhesive hydrogel for biomedicine—principles and design strategies

“…Reproduced with permission. 180 Copyright 2021, American Chemical Society. (B) The introduction of adenine and thymine into the hydrogel drives its adhesion behavior.…”

“…116,186 Moreover, the exciting combination of adhesion theory and biotechnology and the research on adhesion of cell-loaded "living" hydrogels have enriched the field of bio-inspired adhesion, although much endeavor is still to be made. 179,180,212…”

“…Nagahama et al., took inspirations from biological tissues and designed a cadherin‐mediated “living hydrogel” system (Figure 7A). 180 Specifically, individual modified living cells were covalently linked to the hydrogel network via bioorthogonal reactions and cells adhered to each other via cadherin‐mediated adhesion. The resulting hydrogels can form good adhesion and show self‐healing ability.…”

“…(A) Materials and cells are modified to form biological tissue‐inspired hydrogels through bioorthogonal reactions and its adhesion behavior depended on cadherin‐mediated specific cell adhesion. Reproduced with permission 180 . Copyright 2021, American Chemical Society.…”

Covalent Stem Cell-Combining Injectable Materials with Enhanced Stemness and Controlled Differentiation In Vivo

“…We previously proposed a universal technique to construct human cell-based biohybrid hydrogel materials in which azide-modified living cells are chemically (covalently) cross-linked with alkyne-modified polymers via the bio-orthogonal click reaction. − Currently, many researchers have reported various cell-surface modification methods, including chemical conjugation, lipid insertion, and metabolic glycoengineering. , The chemicals can be stably introduced to the cell membrane by chemical conjugation, though it is concerned that this method could affect cell viability by interfering with the function of membrane proteins. In the case of lipid insertion, the chemicals can be inserted physically within cell membranes via hydrophobic interactions without interference with membrane protein’s function.…”