A digital nervous system aiming toward personalized IoT healthcare.

Body area networks (BANs), cloud computing, and machine learning are platforms that can potentially enable advanced healthcare outside the hospital. By applying distributed sensors and drug delivery devices on/in our body and connecting to such communication and decision-making technology, a system for remote diagnostics and therapy is achieved with additional autoregulation capabilities. Challenges with such autarchic on-body healthcare schemes relate to integrity and safety, and interfacing and transduction of electronic signals into biochemical signals, and vice versa. Here, we report a BAN, comprising flexible on-body organic bioelectronic sensors and actuators utilizing two parallel pathways for communication and decision-making. Data, recorded from strain sensors detecting body motion, are both securely transferred to the cloud for machine learning and improved decision-making, and sent through the body using a secure body-coupled communication protocol to auto-actuate delivery of neurotransmitters, all within seconds. We conclude that both highly stable and accurate sensing-from multiple sensors-are needed to enable robust decision making and limit the frequency of retraining. The holistic platform resembles the self-regulatory properties of the nervous system, i.e., the ability to sense, communicate, decide, and react accordingly, thus operating as a digital nervous system.

Highly porous scaffolds of PEDOT:PSS for bone tissue engineering.

Conjugated polymers have been increasingly considered for the design of conductive materials in the field of regenerative medicine. However, optimal scaffold properties addressing the complexity of the desired tissue still need to be developed. The focus of this study lies in the development and evaluation of a conductive scaffold for bone tissue engineering. In this study PEDOT:PSS scaffolds were designed and evaluated in vitro using MC3T3-E1 osteogenic precursor cells, and the cells were assessed for distinct differentiation stages and the expression of an osteogenic phenotype. Ice-templated PEDOT:PSS scaffolds presented high pore interconnectivity with a median pore diameter of 53.6±5.9µm and a total pore surface area of 7.72±1.7m2·g-1. The electrical conductivity, based on I-V curves, was measured to be 140µS·cm-1 with a reduced, but stable conductivity of 6.1µS·cm-1 after 28days in cell culture media. MC3T3-E1 gene expression levels of ALPL, COL1A1 and RUNX2 were significantly enhanced after 4weeks, in line with increased extracellular matrix mineralisation, and osteocalcin deposition. These results demonstrate that a porous material, based purely on PEDOT:PSS, is suitable as a scaffold for bone tissue engineering and thus represents a promising candidate for regenerative medicine. STATEMENT OF SIGNIFICANCE: Tissue engineering approaches have been increasingly considered for the repair of non-union fractions, craniofacial reconstruction or large bone defect replacements. The design of complex biomaterials and successful engineering of 3-dimensional tissue constructs is of paramount importance to meet this clinical need. Conductive scaffolds, based on conjugated polymers, present interesting candidates to address the piezoelectric properties of bone tissue and to induce enhanced osteogenesis upon implantation. However, conductive scaffolds have not been investigated in vitro in great measure. To this end, we have developed a highly porous, electrically conductive scaffold based on PEDOT:PSS, and provide evidence that this purely synthetic material is a promising candidate for bone tissue engineering.

Synthesis of Hetero-bifunctional, End-Capped Oligo-EDOT Derivatives.

Conjugated oligomers of 3,4-ethylenedioxythiophene (EDOT) are attractive materials for tissue engineering applications and as model systems for studying the properties of the widely used polymer poly(3,4-ethylenedioxythiophene). We report here the facile synthesis of a series of keto-acid end-capped oligo-EDOT derivatives (n = 2-7) through a combination of a glyoxylation end-capping strategy and iterative direct arylation chain extension. Importantly, these structures not only represent the longest oligo-EDOTs reported but are also bench stable, in contrast to previous reports on such oligomers. The constructs reported here can undergo subsequent derivatization for integration into higher-order architectures, such as those required for tissue engineering applications. The synthesis of hetero-bifunctional constructs, as well as those containing mixed-monomer units, is also reported, allowing further complexity to be installed in a controlled manner. Finally, we describe the optical and electrochemical properties of these oligomers and demonstrate the importance of the keto-acid in determining their characteristics.

Peptide-directed spatial organization of biomolecules in dynamic gradient scaffolds.

Specific binding peptides are used to spatially organize biomolecule gradients within an electrospun fiber scaffold. Different biomolecule-binding peptide-polymer conjugates are sequentially co-electrospun with a fiber-forming host polymer to generate opposing gradients of peptide functionalization. The binding peptides specifically and non-covalently guide the spatial arrangement of biomolecules into dynamic gradients within the scaffold, mimicking biological gradients found in native tissues.