Application of microtechnologies for the vascularization of engineered tissues

Abstract

Recent advances in medicine and healthcare allow people to live longer, increasing the need for the number of organ transplants. However, the number of organ donors has not been able to meet the demand, resulting in an organ shortage. The field of tissue engineering has emerged to produce organs to overcome this limitation. While tissue engineering of connective tissues such as skin and blood vessels have currently reached clinical studies, more complex organs are still far away from commercial availability due to pending challenges with in vitro engineering of 3D tissues. One of the major limitations of engineering large tissue structures is cell death resulting from the inability of nutrients to diffuse across large distances inside a scaffold. This task, carried out by the vasculature inside the body, has largely been described as one of the foremost important challenges in engineering 3D tissues since it remains one of the key steps for both in vitro production of tissue engineered construct and the in vivo integration of a transplanted tissue. This short review highlights the important challenges for vascularization and control of the microcirculatory system within engineered tissues, with particular emphasis on the use of microfabrication approaches.

Engineering vascularized flaps using adipose-derived microvascular endothelial cells and mesenchymal stem cells

“…The development of three-dimensional constructs relevant for the repair of a variety of tissues is being aggressively pursued, where their vascularization remains a major challenge, requiring a combination of expertise in the fields of developmental biology and tissue engineering (Baiguera, Urbani, & Del Gaudio, 2014;Gauvin, Guillemette, Dokmeci, & Khademhosseini, 2011;Kaully, Kaufman-Francis, Lesman, & Levenberg, 2009;Laschke et al, 2006). Our goal was to provide a simple tissue engineering-based solution for the reconstruction of large soft tissue defects.…”

Experimental approaches to vascularisation within tissue engineering constructs

“…Although modular approach facilitates the formation of large tissue by assembling the functional microtissue through random packing, [166] stacking [156], or directed assembly, [157] technical hurdles to form interconnected 3D macro vascular tree for larger tissue still remains unsolved. [167] Besides, several limitations of modular approach, such as poor Cell sheet Native mechanical property [160] Leakage, [151] requires cells that are proliferative and can produce sufficient ECM [160] Journal of Biomaterials Science, Polymer Edition 705 mechanical integrity of fabricated tissue, limited cell types for incorporation, poor cell viability due to time-consuming fabrication process, and random or uncontrolled structural pattern [160] of grown vasculature or tissue have to be optimized to promote functional vascularization. Comparison of different vascular network fabrication techniques has been summarized in Table 4.…”

In vitro models of tumor vessels and matrix: Engineering approaches to investigate transport limitations and drug delivery in cancer

“…However, as sufficient mass transport within cell-laden biomaterials remains a significant limitation of 3D cultures, these approaches are typically performed in a microscale format and lack the recapitulation of tumor-inherent transport physics. New in vitro platforms that integrate functional vascular structures can help to overcome this limitation [69]. Biomimetic microvascular networks provide controlled experimental platforms to evaluate specific interactions between endothelial cells and tumor environment, improve the design of therapies targeting the vasculature, and assess the efficacy of new drugs or drug delivery strategies [70, 71].…”