Abstract
Bone is a highly vascularized tissue, and its development, maturation, remodeling, and regeneration are dependent on a tight regulation of blood vessel supply. This condition also has to be taken into consideration in the context of the development of artificial tissue substitutes. In classic tissue engineering, bone-forming cells such as primary osteoblasts or mesenchymal stem cells are introduced into suitable scaffolds and implanted in order to treat critical-size bone defects. However, such tissue substitutes are initially avascular. Because of the occurrence of hypoxic conditions, especially in larger tissue substitutes, this leads to the death of the implanted cells. Therefore, it is necessary to devise vascularization strategies aiming at fast and efficient vascularization of implanted artificial tissues. In this review article, we present and discuss the current vascularization strategies in bone tissue engineering. These are based on the use of angiogenic growth factors, the co-implantation of blood vessel forming cells, the ex vivo microfabrication of blood vessels by means of bioprinting, and surgical methods for creating surgically transferable composite tissues.
Highlights
Bone can be divided into an external layer, named cortical bone, and an internal layer, referred to as cancellous bone
Strategies to support vascularization play an important role in the tissue engineering of artificial tissues, especially bone tissue
We focused on four different vascularization strategies
Summary
Bone can be divided into an external layer, named cortical bone, and an internal layer, referred to as cancellous bone. Osteons form functional units that have the so-called haversian canals in the center, which contain nerves and blood vessels [3,4] These osteons with the associated haversian canals are not found in cancellous bone and are not necessary for the blood vessel supply due to the high porosity of this bone compartment. Invading mesenchymal stem cells differentiate into osteoblasts and induce bone formation, as in intramembranous ossification. Vascularization is of crucial importance in both ossification processes as well as further bone formation and in bone remodeling processes In this context, vascularization is necessary for the immigration of mesenchymal stem cells, and, in particular, for the supply of the metabolically active bone tissue with oxygen and nutrients and removal of waste products
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