Realizing tissue integration with supramolecular hydrogels

Biomaterial matrices must permit tissue growth and maturation for the success of tissue regeneration strategies. Naturally, this accommodation is achieved via the dynamic remodeling of a cell's extracellular matrix (ECM). Synthetically, hydrolytic or enzymatic degradation are often engineered into materials for this purpose. More recently, supramolecular interactions have been used to provide a biomimetic and tunable mechanism to facilitate tissue formation via their dynamic and reversible non-covalent interactions. By engineering the mechanical and bioactive properties of a material, supramolecular chemists are able to design permissivity into the construct and facilitate tissue integration in-vivo . Furthermore, via the reversibility of non-covalent interactions, injectability and responsiveness can be designed for enhanced delivery and spatio-temporal control. In this review, we delineate the basic considerations needed when designing permissive supramolecular hydrogels for tissue engineering with an eye toward tissue growth and integration. We highlight three archetypal hydrogel systems that have shown well-documented tissue integration in vivo, and provide avenues to assess tissue in-growth. Careful design and assessment of the biomedical potential of a supramolecular hydrogels can inspire the creation of robust and dynamic implants for new tissue engineering applications.

Statement of significance Tissue engineering and regeneration require careful design of materials to coax the tissue formation process. The materials must provide the cells with a proper environment, but also get out of the way to allow new tissue to form. Normally, biomaterial hydrogels are designed to chemically degrade to permit tissue formation; however, dynamic and reversible supramolecular interactions can be used to facilitate tissue formation and remodelability. Herein we review the common design parameters for supramolecular hydrogels and highlight applications where they have shown the ability to facilitate tissue formation via their dynamic interactions. The review also briefly provides insight into the functionality and control enabled by supramolecular design and the methods one can use to start to assess cell migration and tissue integration.

(c) 2021 Published by Elsevier Ltd on behalf of Acta Materialia Inc.