Accounting for robustness in modeling signal transduction responses.

A classical question in systems biology is to find a Boolean model which is able to predict the observed responses of a signaling network. It has been previously shown that such models can be tailored based on experimental data. While fitting a minimum-size network to the experimentally observed data is a natural assumption, it can potentially result in a network which is not so robust against the noises in the training dataset. Indeed, it is widely accepted now that biological systems are generally evolved to be very robust. Therefore, in the present work, we extended the classical formulation of Boolean network construction in order to put weight on the robustness of the created network. We show that our method results generally in more relevant networks. Consequently, considering robustness as a design principle of biological networks can result in more realistic models.

Sequential application of mineralized electroconductive scaffold and electrical stimulation for efficient osteogenesis.

Osteogenic differentiation is enhanced by many inductive factors including biochemical agents, biomechanical stresses, and electrical stimulation. Regularly studies have focused on one factor at a time, while synergies can promote more effective and functional osteogenesis. Herein, for the first time, functional synergism between application of electrical stimulation and HA nanoparticles was evaluated in osteogenic differentiation. Prepared electrospun biocompatible conductive scaffold by amalgamating chitosan, aniline-pentamer, and hydroxyapatite incorporation was seeded by human bone-marrow-derived mesenchymal stem cells. The cells seeded on the scaffolds with and without hydroxyapatite were exposed to electrical stimulation and subsequently, osteogenic molecular markers and related signaling pathways were investigated. In general, all investigated osteogenic markers (osteocalcin, alkaline phosphatase, osteonectin, and Runx2) were upregulated transcriptionally in the cells seeded on the chitosan-embedded scaffolds. Separate utilization of electrical stimulation or hydroxyapatite-enhanced osteogenesis, while the cells exposed to both stimulators simultaneously, expressed higher levels of some of osteogenic genes significantly. Considering the functions and the positions of the markers in osteogenic signaling pathways, it can be concluded that HA might cooperate in the allocation of stem cells to osteoprogenitors in the early phase of osteogenesis while electrical stimulation helps committed cells with maturation and acquiring functional phenotypes. Altogether investigation of the synergism between different stimulators and exploiting the interactions in an optimized manner could lead to more efficient osteogenesis protocol for effective bone regeneration and tissue engineering. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1200-1210, 2018.

Tissue engineering; strategies, tissues, and biomaterials.

Current tissue regenerative strategies rely mainly on tissue repair by transplantation of the synthetic/natural implants. However, limitations of the existing strategies have increased the demand for tissue engineering approaches. Appropriate cell source, effective cell modification, and proper supportive matrices are three bases of tissue engineering. Selection of appropriate methods for cell stimulation, scaffold synthesis, and tissue transplantation play a definitive role in successful tissue engineering. Although the variety of the players are available, but proper combination and functional synergism determine the practical efficacy. Hence, in this review, a comprehensive view of tissue engineering and its different aspects are investigated.