Abstract

Over the past decades, tissue regeneration with scaffolds has achieved significant progress that would eventually be able to solve the worldwide crisis of tissue and organ regeneration. While the recent advancement in additive manufacturing technique has facilitated the biofabrication of scaffolds mimicking the host tissue, thick tissue regeneration remains challenging to date due to the growing complexity of interconnected, stable, and functional vascular network within the scaffold. Since the biological performance of scaffolds affects the blood vessel regeneration process, perfect selection and manipulation of biological factors (i.e., biopolymers, cells, growth factors, and gene delivery) are required to grow capillary and macro blood vessels. Therefore, in this study, a brief review has been presented regarding the recent progress in vasculature formation using single, dual, or multiple biological factors. Besides, a number of ways have been presented to incorporate these factors into scaffolds. The merits and shortcomings associated with the application of each factor have been highlighted, and future research direction has been suggested.

Highlights

  • Growing tissue in 3D scaffold requires functional and stable vascular network in order to maintain the viability and biological function of a large cell population

  • Injected Matrigel/human umbilical vein endothelial cells (HUVECs) suspension into mice formed mature blood vessels that remained functional till 100 days [86], implanted PLLA scaffolds loaded with human dermal microvascular endothelial cells (HDMECs) in the mice model grew functional microvessels that eventually got connected with the host vasculature [87], and calf pulmonary microvessel-derived ECs grew capillary-like networks under hypoxic condition within 3 days of in vitro culture [88]

  • Migration of cells from host site was identified in the acellular scaffolds, tissue regeneration was unsatisfactory due to the random spatial settlements of the migrated cell population. e incorporation of tissue-specific or vascular cells in the scaffold solved the problem of cell positioning; this approach opens up other complexities

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Summary

Introduction

Growing tissue in 3D scaffold requires functional and stable vascular network in order to maintain the viability and biological function of a large cell population. While the AM technique provides the appropriate biophysical, structural, or topographical cues to the growing blood vessels, the precise selection and manipulation of scaffolding biopolymer, vascular cells, growth factors (GFs), and gene delivery approach significantly affect the formation of mature, stable, and functional vascular network in the tissue scaffolds [2, 3]. Functional vasculature formation with scaffolds demands the perfect selection and use of several factors (i.e., scaffolding biopolymer, vascular cells, GFs, and gene delivery approach). To this end, a literature review is required that would allow us to select and manipulate the factors in the right fashion to obtain the growth of stable vascular network in the engineered construct. Several important issues, advantages, and disadvantages associated with scaffolding biopolymer, vascular cells, GFs, and gene delivery approaches have been summarized, and directions for future research have been included

Additive Manufacturing of Vascularized Construct
Scaffold Fabrication Biomaterial
Selection and Addition of Cells
Findings
Choice and Addition of Growth Factors
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