A 3D-printed hybrid nasal cartilage with functional electronic olfaction

Advances in biomanufacturing techniques have opened the doors to recapitulate human sensory organs such as the nose and ear in vitro with adequate levels of functionality. Such advancements have enabled simultaneous targeting of two challenges in engineered sensory organs, especially the nose: i) mechanically robust reconstruction of the nasal cartilage with high precision and ii) replication of the nose functionality: odor perception. Hybrid nasal organs can be equipped with remarkable capabilities such as augmented olfactory perception. Herein, a proof-of-concept for an odor-perceptive nose-like hybrid, which is composed of a mechanically robust cartilage-like construct and a biocompatible biosensing platform, is proposed. Specifically, 3D cartilage-like tissue constructs are created by multi-material 3D bioprinting using mechanically tunable chondrocyte-laden bioinks. In addition, by optimizing the composition of stiff and soft bioinks in macro-scale printed constructs, the competence of this system in providing improved viability and recapitulation of chondrocyte cell behavior in mechanically robust 3D constructs is demonstrated. Furthermore, the engineered cartilage-like tissue construct is integrated with an electrochemical biosensing system to bring functional olfactory sensations toward multiple specific airway disease biomarkers, explosives, and toxins under biocompatible conditions. Proposed hybrid constructs can lay the groundwork for functional bionic interfaces and humanoid cyborgs7

PH-Responsive DNA Nanolinker Conjugated Hybrid Materials for Electrochemical Microactuator and Biosensor Applications

Copyright © 2018 American Chemical Society. Carbon nanotube (CNT)-based composite or hybrid materials have been broadly used for various biomedical applications such as microactuators, sensors, capacitors, and flexible electronic textiles because of their appealing physical and electrical properties and energy-storage functions. However, to enable application-based specific functionalities (e.g., sensing, responding, and deformation) it is essential that smart stimulus-responsive elements be incorporated into the CNT-based materials. A pioneering approach in integrating stimulus-responsive molecules or linkers is to utilize multistranded DNA structures, such as i-motif DNA with a four-folded structure, which shows reversible conformational changes upon pH alteration. Herein, a pH-responsive CNT-based hybrid material is developed by conjugating i-motif DNA as a pH-responsive nanosized cross-linker. To fabricate microfibers, we spun the i-motif DNA nanolinker-conjugated CNT-based hybrid material in a proton-rich coagulation bath. The attained hybrid microfibers are composed of partially aligned nanowires with â50 nm diameters that are formed in the protonation process by self-assembly of the i-motif DNA nanolinker-conjugated CNT-based hybrid material. The hybrid microfibers showed high electrical conductivity (â27 S/cm), excellent capacitance in a biological medium (â59.9 F/g at pH 5 and â47.8 F/g at pH 8), and stable microactuation without creep behavior. Furthermore, the conjugated i-motif DNA in the hybrid microfibers undergoes conformational changes from a four-folded structure (pH 5) to a random coil structure (pH 8), thus enabling unique dual-pH reversibility in the microfibers, namely switchable microporosity, electrochemical redox activity, and hydrogen peroxide sensing activity. Consequently, the designed stimulus-responsive hybrid microfiber can be used for microactuation and biosensing applications.

3D Printed cartilage-like tissue constructs with spatially controlled mechanical properties

Developing biomimetic cartilaginous tissues that support locomotion while maintaining chondrogenic behavior is a major challenge in the tissue engineering field. Specifically, while locomotive forces demand tissues with strong mechanical properties, chondrogenesis requires a soft microenvironment. To address this challenge, 3D cartilage-like tissue is fabricated using two biomaterials with different mechanical properties: a hard biomaterial to reflect the macromechanical properties of native cartilage, and a soft biomaterial to create a chondrogenic microenvironment. To this end, a bath composed of an interpenetrating polymer network (IPN) of polyethylene glycol (PEG) and alginate hydrogel (MPa order compressive modulus) is developed as an extracellular matrix (ECM) with self-healing properties. Within this bath supplemented with thrombin, human mesenchymal stem cell (hMSC) spheroids embedded in fibrinogen are 3D bioprinted, creating a soft microenvironment composed of fibrin (kPa order compressive modulus) that simulate cartilage's pericellular matrix and allow a fast diffusion of nutrients. The bioprinted hMSC spheroids present high viability and chondrogenic-like behavior without adversely affecting the macromechanical properties of the tissue. Therefore, the ability to locally bioprint a soft and cell stimulating biomaterial inside of a mechanically robust hydrogel is demonstrated, thereby uncoupling the micro- and macromechanical properties of the 3D printed tissues such as cartilage2951FAPESP – Fundação de Amparo à Pesquisa Do Estado De São PauloNWO - Netherlands Organisation for Scientific Research2017/02913‐41432