Abstract

Since the emergence of regenerative medicine and tissue engineering more than half a century ago, one obstacle has persisted: the in vitro creation of large-scale vascular tissue (>1 cm3) to meet the clinical needs of viable tissue grafts but also for biological research applications. Considerable advancements in biofabrication have been made since Weinberg and Bell, in 1986, created the first blood vessel from collagen, endothelial cells, smooth muscle cells and fibroblasts. The synergistic combination of advances in fabrication methods, availability of cell source, biomaterials formulation and vascular tissue development, promises new strategies for the creation of autologous blood vessels, recapitulating biological functions, structural functions, but also the mechanical functions of a native blood vessel. In this review, the main technological advancements in bio-fabrication are discussed with a particular highlights on 3D bioprinting technologies. The choice of the main biomaterials and cell sources, the use of dynamic maturation systems such as bioreactors and the associated clinical trials will be detailed. The remaining challenges in this complex engineering field will finally be discussed.

Highlights

  • After many years of research in the field of engineering and regenerative medicine, an obstacle remains: the design and construction of vascularized large-scale in vitro tissues (>1 cm3) for biological studies and transplantation

  • These layers are composed of endothelial cells (ECs), smooth muscle cells (SMCs) and fibroblasts (FBs), respectively, trapped in a highly organized extracellular matrix (ECM) mainly composed of type I collagen, type III collagen and elastin

  • Vascular Tissue Engineering an Biofabrication despite advances in pharmacology, material science and device manufacturing, these synthetic tissue-engineering vascular grafts (TEVG) had not significantly reduced overall mortality and morbidity (Nugent and Edelman, 2003). They were exclusively composed of acellular synthetic polymers and, as known today, the natural formation and maintenance of functional blood vessels is an active cell-driven process caused by the growth, death and migration of cells inside biomaterials, as well as by structural changes in tissues through the production and degradation of ECM by the cells themselves (Epstein et al, 1994; McGrath et al, 2005; Touyz, 2005)

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Summary

INTRODUCTION

After many years of research in the field of engineering and regenerative medicine, an obstacle remains: the design and construction of vascularized large-scale in vitro tissues (>1 cm3) for biological studies and transplantation. Vascular Tissue Engineering an Biofabrication despite advances in pharmacology, material science and device manufacturing, these synthetic TEVGs had not significantly reduced overall mortality and morbidity (Nugent and Edelman, 2003) They were exclusively composed of acellular synthetic polymers and, as known today, the natural formation and maintenance of functional blood vessels is an active cell-driven process caused by the growth, death and migration of cells inside biomaterials, as well as by structural changes in tissues through the production and degradation of ECM by the cells themselves (Epstein et al, 1994; McGrath et al, 2005; Touyz, 2005). We will present the remaining challenges of vascular tissue engineering as well as the potential solutions and future perspectives in this highly dynamic field of research (Figure 1)

CHALLENGES AND REQUIREMENTS OF AN IDEAL LARGE BLOOD VESSEL
ANATOMY OF VASCULAR TISSUE
Intima
Adventice
BIOMATERIALS
BIOFABRICATION TECHNIQUES
Early Tissue-Engineered Blood Vessel
Traditional Biofabrication Techniques
Advanced Biofabrication Technique
TISSUE MATURATION
Bioreactor Functions
Bioreactors Design
Bioreactors Strategies for Maturation
CLINICAL TRIALS
FUTURE DIRECTIONS
Findings
10 CONCLUSION
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