Boronic acids (BA) are known for their ability to reversibly interact with the diol groups, a common motif of biomolecules including sugars and ribose. Besides the structural versatility, some derivatives can undergo a sharp inversion in the state of hydration in synchronization with the molecular recognitions. This feature translates into many creative modes for switching or fine-tuning the hydration and more complex molecular assemblies in a way interactive with biology. I will provide an overview of our recent efforts on the related applications with focuses on a smart insulin delivery system and sialic acid interactions relevant to cancer diagnosis and treatment.

Tissue adhesives have been widely used for the surgical operation to avoid air leakage or bleeding. Commercial adhesives have some disadvantages on bonding strength and biocompatibility. To overcome these clinical problems, we have designed hydrophobically-modified Alaska pollock-derived gelatins (hm-ApGltns)-based tissue adhesives because of low transition temperature of ApGltn. Resulting hm-ApGltn adhesives showed significantly high burst strength compared with original ApGltn and commercial fibrin adhesives when applied to blood vessel, intestine and lung surface tissue under wet condition. Also, hm-ApGltn adhesives were enzymatically degraded without sever inflammation in rat subcutaneous tissue. Therefore, hm-ApGltn adhesives can be applied to various surgical field, especially to minimally-invasive therapy.

Native tissue varies compositionally in its chemical, mechanical, and cellular makeup in both 3D space and time (i.e., 4D). Despite its importance in driving all living processes, such 4D complexity is not captured in traditional cell culture platforms (e.g., petri dishes, static/homogenous biomaterials). In this talk, I will discuss some of our group’s recent successes in reversibly modifying both the chemical and physical aspects of synthetic cell culture platforms with user-defined spatiotemporal control, regulating cell-biomaterial interactions through user-programmable Boolean logic, and engineering large-scale microvascular networks. Results will highlight our ability to modulate intricate cellular behavior including stem cell differentiation, protein secretion, and cell-cell interactions in 4D.

Smart polymers which exhibit special functions in response to external conditions have attracted more and more attention. In this presentation, I will introduce a biomarker enrichment technology for the detection of COVID-19 using temperature-responsive polymers.

In order to apply mRNA and nucleic acids as "medicine", it is essential to develop a "drug delivery system (DDS)" to deliver mRNA to the cytoplasm. We introduce environment-responsive lipid-like materials (SS-cleavable and pH-activated lipid-like materials) that we are developing to realize nucleic acid/mRNA drug discovery. In addition to the tertiary amine structure, this material is designed so that the nanoparticles are actively disintegrated by being cleaved in the reducing environment of the cytoplasm. In this presentation, we will introduce a series of these development processes and their applicability to RNA and nucleic acid introduction technology.

Biological functions are regulated by mechanical forces; this knowledge is used for biomaterials design. Conventionally, the impact of material elasticity of cellular activities and fates were the major topics, but recent trend is moving onto how cells feel and respond to the dynamic nature of materials as native tissues are viscoelastic. In this presentation, I will introduce cellular mechanobiological responses on liquid-based dynamic materials and their potential applications.

Tissue form and function within native extracellular matrices arises from dynamic feedback between cells and materials. Building similar dynamics into synthetic biomaterials remains a considerable challenge. Here I discuss ways in which cellular activity and materials properties can be varied together to better mimic this dynamic interplay. I will introduce designer microgel suspensions where the materials properties spatially direct stem cell fate. Integration of enzymes within these microgels can be used to locally attenuate gas activity, thereby providing temporal control over second messengers. The interconnected pore space can be tuned through incorporating “filler” materials to further guide cell activity over prolonged culture. Overall, cell-laden granular materials provide a unique scaffolding where materials parameters and cell activity can be directed with spatiotemporal control.

Tissue engineering has been developed as an attractive approach to treat the diseases and defects that are difficult to be treated by conventional drug administration, prosthesis and organ transplantation. Tissue engineering can also be applied for regeneration of resected tissues after cancer therapy. Scaffolds play an important role in tissue engineering. They can control cell functions and provide temporary support for regeneration of functional new tissues and organs. We have prepared a few types of porous scaffolds of biodegradable polymers and biomimetic matrices and their composite scaffolds with nanoparticles. These scaffolds have been used for tissue engineering of cartilage, skin, bone, muscle and cancer therapy applications.