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

Abstract

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.

Manufacturing, characterization, and degradation of a poly(lactic acid) warp-knitted spacer fabric scaffold as a candidate for tissue engineering applications

“…10 Several technologies can also be combined to optimize scaffold properties for the regeneration of a specific tissue 53 or imitate in vivo -like tissue development processes. 54…”

“…Moreover, the work of Entezari et al , 67 who demonstrated numerically the possibility of using weak biomaterials in modular scaffolds for repairing large bone defects, with only few percent of strain being sufficient to promote osteogenesis, supports our proposed use of the present scaffold for the repair of non and load-bearing tissues. The bioabsorbable scaffold developed here can also be used in bottom-up tissue engineering strategies, 54,68 culturing different cell types on different fabric layers, which assembled could better mimic the native tissue environment and improve tissue healing. Even though some scaffold requirements are specific to each tissue and a single scaffold design is unlikely to meet the requirements of all human tissues; we propose bioabsorbable warp-knitted spacer fabrics as versatile platform for scaffold manufacturing.…”

“…With only few engineered tissues successfully used for clinical purposes, 54 the present work describes the design and manufacturing of a 3D textile scaffold able to support cell attachment and growth, and gives insights on the properties of bioabsorbable polymeric yarns during degradation and their potential effects on cell behaviour, thus contributing to the further development of bioabsorbable tissue engineering scaffolds.…”

Traction of 3D and 4D Printing in the Healthcare Industry: From Drug Delivery and Analysis to Regenerative Medicine

“…Adjusting bottom-up processes (i.e., the directed or self-assembly of a scaffold from smaller elements or modules, feasibly with various modules aimed to perform distinct functions) for tissue engineering is a major challenge, and numerous attempts to print synthetic biodegradable/biocompatible scaffolds have been made since the first use of fused deposition modeling for tissue engineering applications. , Here, 3D bioprinting is a promising recent advancement with the ability to simultaneously deposit single or blended supportive matrices and living cells (collectively called bioink) and the potential to assist in the fabrication of well-organized 3D vascular networks. ,,, Various types of rapid prototyping methods have been established to enable the creation of macroscopic structures of deposited biomaterials, including gel deposition using syringe-based approaches, stereolithography, and solid freeform manufacturing. While both 3D printing and 3D bioprinting use a 3D prototype to fabricate constructs in a layer-by-layer manner, 3D bioprinting encompasses the use of both cell-loaded bioinks and other biological agents to build a living cell-laden scaffold.…”

Engineering Biological Tissues from the Bottom-Up: Recent Advances and Future Prospects

“…Over the years, bottom-up tissue engineering was developed to take the place of top-down tissue engineering [17,18]. This method is usually used to fabricate function units, such as cell aggregations and cell sheets, which constructs bigger tissues or organs by using the modular assembly approach [1,11,16,19,20].…”