Responsive Polymers as Cell Surface Modifiers and 3D Healable Microenvironments

The interplay between cells and biomaterials constitutes a fertile ground to probe specific cellular functions and cues for therapeutic and research purposes. “Smart” materials encompass an extensive library that can lead to the design of dynamic multi-responsive constructs with great importance in the biomedical field. This work aims to describe diverse strategies on the modification of biological interfaces with synthetic polymers to promote the assembly of living cells and the design of multi-responsive healable cell-encapsulating constructs with interest in 3D in vitro modelling, drug delivery, cell-based therapies and tissue engineering. In the first part, cell membrane engineering approaches are introduced to create a responsive platform for the accelerated and simple formation of cellular aggregates/spheroids, and to study polymer-cell interactions by exploring biorthogonal ligand-receptor multivalent interactions under different conditions. Specifically, boronic acid- and succinimide-based copolymers were first synthesised and fully characterised by physicochemical methods, and found to bind covalently to natural moieties present on the membrane of several cell lines, which can regulate the development of cell spheroids and act as self-supporting “cellular glues”. The second part of the project is dedicated to the development of multi-responsive self-healing hydrogel nanocomposites for biomedical applications, where we further expanded the dynamic crosslinking nature of boronate ester bonds. The proposed gels could be prepared almost instantly, exhibited photo- and thermoreversible transient sol-gel type of transition with excellent healing properties, and no toxicity, which allows the system to be used as a versatile biologic delivery matrix. In summary, the results highlight novel and straightforward approaches that may pave the way to implement a biomaterial-cell platform with broad biotechnological applications