*Review* **Modular Strategies to Build Cell-Free and Cell-Laden Sca**ff**olds towards Bioengineered Tissues and Organs**

**Aurelio Salerno 1,\*, Giuseppe Cesarelli 1,2, Parisa Pedram 1,2 and Paolo Antonio Netti 1,2,3**


Received: 30 September 2019; Accepted: 28 October 2019; Published: 1 November 2019

**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.

**Keywords:** additive manufacturing; bioprinting; drug delivery; microparticles; scaffold; soft lithography; vascularization
