A Paradigm Shift in Tissue Engineering: From a Top–Down to a Bottom–Up Strategy

Tissue engineering (TE) was initially designed to tackle clinical organ shortage problems. Although some engineered tissues have been successfully used for non-clinical applications, very few (e.g., reconstructed human skin) have been used for clinical purposes. As the current TE approach has not achieved much success regarding more broad and general clinical applications, organ shortage still remains a challenging issue. This very limited clinical application of TE can be attributed to the constraints in manufacturing fully functional tissues via the traditional top–down approach, where very limited cell types are seeded and cultured in scaffolds with equivalent sizes and morphologies as the target tissues. The newly proposed developmental engineering (DE) strategy towards the manufacture of fully functional tissues utilises a bottom–up approach to mimic developmental biology processes by implementing gradual tissue assembly alongside the growth of multiple cell types in modular scaffolds. This approach may overcome the constraints of the traditional top–down strategy as it can imitate in vivo-like tissue development processes. However, several essential issues must be considered, and more mechanistic insights of the fundamental, underpinning biological processes, such as cell–cell and cell–material interactions, are necessary. The aim of this review is to firstly introduce and compare the number of cell types, the size and morphology of the scaffolds, and the generic tissue reconstruction procedures utilised in the top–down and the bottom–up strategies; then, it will analyse their advantages, disadvantages, and challenges; and finally, it will briefly discuss the possible technologies that may overcome some of the inherent limitations of the bottom–up strategy.

Modular Strategies to Build Cell-Free and Cell-Laden Scaffolds towards Bioengineered Tissues and Organs

Engineering three-dimensional (3D) scaffolds for functional tissue and organ regeneration is a major challenge of the tissue engineering (TE) community. Great progress has been made in developing scaffolds to support cells in 3D, and to date, several implantable scaffolds are available for treating damaged and dysfunctional tissues, such as bone, osteochondral, cardiac and nerve. However, recapitulating the complex extracellular matrix (ECM) functions of native tissues is far from being achieved in synthetic scaffolds. Modular TE is an intriguing approach that aims to design and fabricate ECM-mimicking scaffolds by the bottom-up assembly of building blocks with specific composition, morphology and structural properties. This review provides an overview of the main strategies to build synthetic TE scaffolds through bioactive modules assembly and classifies them into two distinct schemes based on microparticles (µPs) or patterned layers. The µPs-based processes section starts describing novel techniques for creating polymeric µPs with desired composition, morphology, size and shape. Later, the discussion focuses on µPs-based scaffolds design principles and processes. In particular, starting from random µPs assembly, we will move to advanced µPs structuring processes, focusing our attention on technological and engineering aspects related to cell-free and cell-laden strategies. The second part of this review article illustrates layer-by-layer modular scaffolds fabrication based on discontinuous, where layers’ fabrication and assembly are split, and continuous processes.

Analysis of Ledger-Stand Joints in the Aluminum Modular Scaffold

This paper concerns an approach to model the ledger-stand joints of modular scaffolds. Based on the analysis of the working range of the ledger (represented by a linear relationship between load and displacement), two models of the ledger-stand joint are analysed: first - with flexibility joints and second - with rigid joints and with a transition part of lower stiffness. Parameters are selected based on displacement measurements and numerical analyses of joints, then they are verified. On the basis of performed research, it can be stated that both methods of joint modelling recommended in this paper, can be applied in engineering practices.

Historical Survey

Chapter 2 overviews the historical development and past research into temporary structures from 1970 up to 2016 and describe the various problems that have occurred necessitating changes to traditional design and construction techniques. The survey covers tubular, proprietary and modular scaffolds, bridge falsework as well as bridge construction equipment. Particular areas emphasised are the changes introduced by the use of advanced structural analysis techniques and the need for changes in procedures following the analyses of collapses of temporary structures. An overview of various solutions is presented, including the use of different materials (steel, aluminium, timber and bamboo). The chapter shows that same analysis procedures are used for these different materials. The chapter then overviews the actions acting on temporary structures such as permanent loads and variable construction loads and finishes with an introduction to failures of falsework and scaffolding structures.

Genome Regulation by Long Non-Coding RNAs

The discovery of extensive transcription of long noncoding RNAs (lncRNAs) provide an important new perspective on the centrality of RNA in gene regulation. Discussions will cover genome-scale strategies to discover and characterize lncRNAs. An emerging theme from multiple model systems is that lncRNAs form extensive networks of ribonucleoprotein (RNP) complexes with numerous chromatin regulators, and both control and target these enzymatic activities to appropriate locations in the genome. Consistent with this notion, long non-coding RNAs can function as modular scaffolds to specify higher order organization in RNP complexes and in chromatin states. More recently, lncRNAs have been found to control post-transcriptional processes and signal transduction as well. The importance of these modes of regulation is underscored by the newly recognized roles of long RNAs in developmental patterning and cancer. Disclosures: Chang: RaNA Therapeutics: Membership on an entity’s Board of Directors or advisory committees.