Multifunctional tissue-mimetic hydrogels for advanced bioelectronics

Abstract

Hydrogels, a kind of biomimetic soft material, have emerged as a promising material candidate for the tissue repair or replacement, and bioelectronic interfaces because of their similarities to biological tissues and versatility in electrical, mechanical and biofunctional engineering. Natural load bearing tissues demonstrate many characteristics that are difficult to replicate with synthetic hydrogels. For instance, tendons involve unique anisotropic and hierarchical microstructure. They contain ~60 wt. % of water while exhibiting high moduli (at the gigapascal level) and strengths (55 to 120 MPa). In this thesis, we first fabricated multifunctional tendon-mimetic hydrogels constructed from anisotropic assembly of ANF composites. The stiff nanofibers and soft polyvinyl alcohol in these anisotropic composite hydrogels (ACHs) could nicely imitate the structural interplay between aligned collagen fibers and proteoglycans in tendons. The ACHs exhibit a high modulus of ~1.1 GPa, an ultimate strength of ~72 MPa, fracture toughness of 7333 J/m2, and some dynamic mechanical behaviors resembling those of natural tendons. These excellent static and dynamic mechanical properties have not been achieved with previous synthetic hydrogels. The surfaces of ACHs were then functionalized with bioactive molecules to present biophysical cues for the modulation of morphology, phenotypes, and other behaviors of attached cells. Moreover, some typical bioelectronic components could be integrated on ACHs with robust interfacial coupling, enabling in situ sensing of various physiological parameters. Hydrogel electronics find widespread applications in healthcare monitoring, medical diagnosis, and disease therapies. However, achieving a hydrogel platform with high mechanical compliance and robustness remains challenging. In this thesis, we report an ultrathin and robust hydrogel material designed through a biomimetic microstructure of a fibrillar network with high nodal strength and low connectivity. Theoretical simulations demonstrate that these features at fibrillar joints can effectively control macroscopic mechanical properties, meeting these requirements simultaneously under a constant level of water content. Indeed, the ultrathin hydrogel exhibited a low modulus of ~600 kPa, high tensile strength of ~14 MPa, high fracture energy of ~21573 J/m² and strain-stiffing characteristic at a thickness of 10 μm, providing advantageous conformity and manufacturability for applications in skin or tissue bioelectronic interfaces. We show that the further integration of patterned conductive materials, such as metals and conductive polymers, can be used as electrodes with favorable interfacial impedance for electrophysiological applications, including wearable skin sensors, implantable brain-machine interfaces (BMIs), and peripheral nerve interfaces (PNIs). The biomimetic design and mechanistic insights may open new doors for biomaterials innovation and bioelectronics architecture.