Microengineered platforms for co-cultured mesenchymal stem cells towards vascularized bone tissue engineering

Abstract

Bone defects are common disease requiring thorough treatments since the bone is a complex vascularized tissue that is composed of multiple cell types embedded within an intricate extracellular matrix (ECM). For past decades, tissue engineering using cells, proteins, and scaffolds has been suggested as one of the promising approaches for effective bone regeneration. Recently, many researchers have been interested in designing effective platform for tissue regeneration by orchestrating factors involved in microenvironment around tissues. Among factors affecting bone formation, vascularization during bone development and after minor insults via endochondral and intramembranous ossification is especially critical for the long-term support for functional bone. In order to create vascularized bone constructs, the interactions between human mesenchymal stem cells (MSCs) and endothelial cells (ECs) have been investigated using both direct and indirect co-culture studies. Recently, various culture methods including micropatterning techniques, three dimensional scaffolds, and microfluidics have been developed to create micro-engineered platforms that mimic the nature of vascularized bone formation, leading to the creation of functional bone structures. This review focuses on MSCs co-cultured with endothelial cells and microengineered platforms to determine the underlying interplay between co-cultured MSCs and vascularized bone constructs, which is ultimately necessary for adequate regeneration of bone defects.

Bone physiology as inspiration for tissue regenerative therapies

“…using ASCs) technologies. The characterization of the effect of different co-culture setups is another aspect that is still in need of further in-depth study; efforts to perform relevant characterization have relied on micropatterning strategies (mostly targeting 2D culture systems), use of transwell systems, and microfluidics to generate multicompartment structures [209]. Future optimization of such setups will allow further elucidation of the role of distinct culture setups on the synergic role of vasculature formation and bone tissue development on 3D/4D relevant structures, which will be organized in ECM-like structural organization and temporarily-controlled remodeling.…”

3D-Bioprinting Strategies Based on In Situ Bone-Healing Mechanism for Vascularized Bone Tissue Engineering

“… Vascular networks within the hierarchical bone structure and bone anatomy in cellular level. Adapted from [ 20 ], published by Springer. …”

3D Bioprinting and In Vitro Cardiovascular Tissue Modeling

“…3D bioprinting has been mainly utilized only for fabricating tissue constructs (e.g., skin, bone, blood vessels, liver, heart tissue, and cartilage tissue) [ 38 , 50 , 105 , 106 , 107 , 108 , 109 , 110 , 111 ]; however, there is huge potential to integrate microfluidic systems and 3D printed tissue models because of the process flexibility offered by multi-materials. In addition, this integrated system would enable the elucidation of the physiological phenomena (e.g., interactions between immune cells/blood and tissues) on the 3D tissue models that occur in our body system.…”