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

Abstract

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.

Innovative Human Three-Dimensional Tissue-Engineered Models as an Alternative to Animal Testing

“…Recently, the combination of several techniques of production or maturation, such as induced pluripotent stem cells, organoids, bioprinting, composite hydrogels, organ-on-chip, microphysiological systems, mechanical stimuli, innervation etc., (e.g., [ 312 , 313 , 314 , 315 , 316 ]), gave us the opportunity to produce a large spectra of complex organs. These organs could also be used for various applications such as potential transplantation (e.g., [ 317 ]) or disease modeling (e.g., [ 318 , 319 , 320 ]).…”

Review on Computer-Aided Design and Manufacturing of Drug Delivery Scaffolds for Cell Guidance and Tissue Regeneration

“…The scaffold model was subsequently divided into multiple layers for fabrication. AM techniques are modular approaches based on the assembly/sintering of layered structures obtained by continuous or discontinuous processes ( Salerno et al, 2019 ). The advantages of employing AM processes, such as 3D printing, include the capability of precisely controlling the spatial loading of an active molecule within even minute quantities and generate multiple delivery profiles by creating different depots and complex geometries ( Caballero-Aguilar et al, 2020 ; Jacob et al, 2020 ).…”

Functionalization of Silk Fibers by PDGF and Bioceramics for Bone Tissue Regeneration

“…In addition to scaffold designs mimicking the microenvironment of the bone in terms of biomaterial selection, it also is desirable to functionalize the scaffold with an additional component that promotes growth of bone cells, has a positive effect on the osteogenic differentiation of the immigrated cells, and additionally supports the vascularization of the scaffold. For a successful ingrowth of a tissue engineering construct and the preservation of the function of the implant within the body, a rapid vascularization of the scaffold is absolutely essential [31,32].…”