Engineering clinically relevant volumes of vascularized bone

Abstract

Vascularization remains one of the most important challenges that must be overcome for tissue engineering to be consistently implemented for reconstruction of large volume bone defects. An extensive vascular network is needed for transport of nutrients, waste and progenitor cells required for remodelling and repair. A variety of tissue engineering strategies have been investigated in an attempt to vascularize tissues, including those applying cells, soluble factor delivery strategies, novel design and optimization of bio-active materials, vascular assembly pre-implantation and surgical techniques. However, many of these strategies face substantial barriers that must be overcome prior to their ultimate translation into clinical application. In this review recent progress in engineering vascularized bone will be presented with an emphasis on clinical feasibility.

Keywords: bone tissue engineering; clinical applications; vascularization.

Figure 1

Section of porcine rib stained with haematoxylin and eosin demonstrating the microstructure of bone. Arrows denote Haversian canals. Scale bar represents 100 μm.

Figure 2

MicroCT images of cranial defect sites at 4 weeks (A–D) and 12 weeks (E–H) display evidence of bone and blood vessel formation. Microfil perfusion was performed to visualize blood vessels for 4 week samples but not 12 week samples. Groups include blank (A and E), VEGF only (B and F), BMP-2 only (C and G) and dual VEGF/BMP-2 (D and H). Scale bar represents 200 μm for all panels. Figure reproduced with permission, from Patel et al. .

Figure 3

(Top) Poly(methyl methacrylate) chambers designed to mimic the size and shape of the mental protuberance of the mandible. (Below) Chambers filled with autologous morselized bone graft were implanted in sheep rib with the open side exposed to the cambium surface of the periosteum. Scale bar represents 2 cm. Figure reproduced with permission, from Cheng et al. .