3D Printable Electrically Conductive Hydrogel Scaffolds for Biomedical Applications: A Review.

Electrically conductive hydrogels (ECHs), an emerging class of biomaterials, have garnered tremendous attention due to their potential for a wide variety of biomedical applications, from tissue-engineered scaffolds to smart bioelectronics. Along with the development of new hydrogel systems, 3D printing of such ECHs is one of the most advanced approaches towards rapid fabrication of future biomedical implants and devices with versatile designs and tuneable functionalities. In this review, an overview of the state-of-the-art 3D printed ECHs comprising conductive polymers (polythiophene, polyaniline and polypyrrole) and/or conductive fillers (graphene, MXenes and liquid metals) is provided, with an insight into mechanisms of electrical conductivity and design considerations for tuneable physiochemical properties and biocompatibility. Recent advances in the formulation of 3D printable bioinks and their practical applications are discussed; current challenges and limitations of 3D printing of ECHs are identified; new 3D printing-based hybrid methods for selective deposition and fabrication of controlled nanostructures are highlighted; and finally, future directions are proposed.

Resilin-mimetics as a smart biomaterial platform for biomedical applications.

Intrinsically disordered proteins have dramatically changed the structure-function paradigm of proteins in the 21st century. Resilin is a native elastic insect protein, which features intrinsically disordered structure, unusual multi-stimuli responsiveness and outstanding resilience. Advances in computational techniques, polypeptide synthesis methods and modular protein engineering routines have led to the development of novel resilin-like polypeptides (RLPs) including modular RLPs, expanding their applications in tissue engineering, drug delivery, bioimaging, biosensors, catalysis and bioelectronics. However, how the responsive behaviour of RLPs is encoded in the amino acid sequence level remains elusive. This review summarises the milestones of RLPs, and discusses the development of modular RLP-based biomaterials, their current applications, challenges and future perspectives. A perspective of future research is that sequence and responsiveness profiling of RLPs can provide a new platform for the design and development of new modular RLP-based biomaterials with programmable structure, properties and functions.

Tuning the Hierarchical Structure and Resilience of Resilin-like Polypeptide Hydrogels Using Graphene Oxide.

Resilin-like polypeptides (RLPs) are an important class of intrinsically disordered multistimuli-responsive bioelastomers. The nanostructure of RLPs in solution has been extensively studied in the past few years, from dilute to molecular crowding conditions, and with the addition of rigid biopolymers. Modification of the hierarchical network structure of RLP hydrogels using graphene oxide (GO) as an additive is a burgeoning prospect for their application in the bioelectronic and biomedical fields. In this work, we systemically study the influence of incorporating GO into RLP (Rec1) hydrogels for tuning their physicochemical properties and understanding the gel-cell interactions. The nature of GO interaction with the Rec1 hydrogel is deduced from the change in structure and properties. Contrast-matching small-angle and ultra-small-angle neutron-scattering techniques were used to investigate the network structure of the Rec1 hydrogel and how this structure is modified in the presence of GO. Incorporation of GO in the Rec1 hydrogel matrix results in an increase in the micromechanical resilience, equilibrium water swelling ratio, micropore size, cross-linked domain size; with a decrease in the cross-link density, mass fractal cluster size, local compressive elastic modulus, and cell inert characteristics. These property combinations achieved with the addition of GO further open up the available structure-property design window for RLP applications.

Multi-responsive biomaterials and nanobioconjugates from resilin-like protein polymers.

Nature, through evolution over millions of years, has perfected materials with amazing characteristics and awe-inspiring functionalities that exceed the performance of man-made synthetic materials. One such remarkable material is native resilin - an extracellular skeletal protein that plays a major role in the jumping, flying, and sound production mechanisms in many insects. It is one of the most resilient (energy efficient) elastomeric biomaterials known with a resilience of ∼97% and a fatigue life in excess of 300 million cycles. Recently, resilin-like polypeptides (RLPs) with exquisite control over the amino acid sequence (comprising repeat resilin motifs) and tuneable biological properties and/or functions have been generated by genetic engineering and cloning techniques. RLPs have been the subject of intensive investigation over a decade and are now recognized to be multi-functional and multi-stimuli responsive; including temperature (exhibiting both an upper and a lower critical solution temperature), pH, moisture, ion and photo-responsive with tuneable photo-physical properties. Such unusual multi-stimuli responsiveness has scarcely been offered and reported for either synthetic or natural biopolymers. Furthermore, the directed molecular self-assembly property of RLPs also exhibits promise as efficient templates for the synthesis and stabilization of metal nanoparticles. These developments and observations reveal the opportunities and new challenges for RLPs as novel materials for nanotechnology, nanobiotechnology and therapeutic applications. In this review, we discuss and highlight the design and synthesis of different RLPs, their unique molecular architecture, advanced responsive behaviour, and functionality of hydrogels, solid-liquid interfaces, nanoparticles and nanobioconjugates derived from RLPs.