An Overview of In Vitro Biological Neural Networks for Robot Intelligence.

In vitro biological neural networks (BNNs) interconnected with robots, so-called BNN-based neurorobotic systems, can interact with the external world, so that they can present some preliminary intelligent behaviors, including learning, memory, robot control, etc. This work aims to provide a comprehensive overview of the intelligent behaviors presented by the BNN-based neurorobotic systems, with a particular focus on those related to robot intelligence. In this work, we first introduce the necessary biological background to understand the 2 characteristics of the BNNs: nonlinear computing capacity and network plasticity. Then, we describe the typical architecture of the BNN-based neurorobotic systems and outline the mainstream techniques to realize such an architecture from 2 aspects: from robots to BNNs and from BNNs to robots. Next, we separate the intelligent behaviors into 2 parts according to whether they rely solely on the computing capacity (computing capacity-dependent) or depend also on the network plasticity (network plasticity-dependent), which are then expounded respectively, with a focus on those related to the realization of robot intelligence. Finally, the development trends and challenges of the BNN-based neurorobotic systems are discussed.

A clamp-free micro-stretching system for evaluating the viscoelastic response of cell-laden microfibers.

Viscoelastic hydrogel microfibers have extensive applications in tissue engineering and regenerative medicine, however, their viscoelasticity is still difficult to be directly characterized because microfiber-specific measuring system is lacking for quantitative studies. In this paper, we develop a two-probe micro-stretching system to quantitatively investigate viscoelasticity of the microfiber by evaluating the storage and loss modulus: E' and E″. A liquid bridge-based fixation method enables single microfiber to be easily fixed to be stably stretched by a two-probe actuator. Afterward, multi-frequency stretching force loading is automatically implemented based on real-time force control, and the resulting stress and strain in the frequency spectrum are measured to evaluate the E' and E″ of pure GelMA, alginate-GelMA composite and GelMA core-alginate shell microfibers. The measured E' and E″ are verified by the response of NIH/3T3 fibroblast cells to the composite microfibers with different alginate concentrations. Moreover, benefiting from the low-damaged stretching process, our system can also detect the difference of the E' and E″ between two cellular processes including growth and differentiation of the aligned mesenchymal stem cells in the same one core-shell microfiber. These results all show that our proposed system provides a valuable reference tool for biomaterials design, the study of cell-matrix interaction and disease etiology from the perspective of mechanics.

Bio-inspired engineering of a perfusion culture platform for guided three-dimensional nerve cell growth and differentiation.

Collagen provides a promising environment for 3D nerve cell culture; however, the function of perfusion culture and cell-growth guidance is difficult to integrate into such an environment to promote cell growth. In this paper, we develop a bio-inspired design method for constructing a perfusion culture platform for guided nerve cell growth and differentiation in collagen. Based on the anatomical structure of peripheral neural tissue, a biomimetic porous structure (BPS) is fabricated by two-photon polymerization of IP-Visio. The micro-capillary effect is then utilized to facilitate the self-assembly of cell encapsulated collagen into the BPS. 3D perfusion culture can be rapidly implemented by inserting the cell-filled BPS into a pipette tip connected with syringe pumps. Furthermore, we investigate the nerve cell behavior in the BPS. 7-channel aligned cellular structures surrounded with a Schwann cell layer can be stably formed after a long-time perfusion culture. Differentiation of PC12 cells and mouse neural stem cells shows 3D neurite outgrowth alignment and elongation in collagen. The calcium activities of differentiated PC12 cells are visualized for confirming the preliminary formation of cell function. These results demonstrate that the proposed bio-inspired 3D cell culture platform with the advantages of miniaturization, structure complexity and perfusion has great potential for future application in the study of nerve regeneration and drug screening.