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Review
. 2015 Mar;43(3):718-29.
doi: 10.1007/s10439-015-1253-3. Epub 2015 Jan 24.

Vascularization in bone tissue engineering constructs

Ángel E Mercado-Pagán  1 , Alexander M Stahl, Yaser Shanjani, Yunzhi Yang
Affiliations
Review

Vascularization in bone tissue engineering constructs

Ángel E Mercado-Pagán et al. Ann Biomed Eng. 2015 Mar.

Abstract

Vascularization of large bone grafts is one of the main challenges of bone tissue engineering (BTE), and has held back the clinical translation of engineered bone constructs for two decades so far. The ultimate goal of vascularized BTE constructs is to provide a bone environment rich in functional vascular networks to achieve efficient osseointegration and accelerate restoration of function after implantation. To attain both structural and vascular integration of the grafts, a large number of biomaterials, cells, and biological cues have been evaluated. This review will present biological considerations for bone function restoration, contemporary approaches for clinical salvage of large bone defects and their limitations, state-of-the-art research on the development of vascularized bone constructs, and perspectives on evaluating and implementing novel BTE grafts in clinical practice. Success will depend on achieving full graft integration at multiple hierarchical levels, both between the individual graft components as well as between the implanted constructs and their surrounding host tissues. The paradigm of vascularized tissue constructs could not only revolutionize the progress of BTE, but could also be readily applied to other fields in regenerative medicine for the development of new innovative vascularized tissue designs.

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Conflict of interest statement

Conflict of interest

The authors have no conflicts of interest with respect to this review.

Figures

Figure 1
Figure 1
Schematic of the bone structure. Bone is highly vascularized, from the intramedullary cavity to the periosteal mineral matrix.
Figure 2
Figure 2
Hierarchical levels in bone vasculature. Large vessels branch out internally into smaller capillary units to perfuse blood throughout the scaffold.
Figure 3
Figure 3
Current techniques used for the repair of vascularized bones. (A) In vascularized fibular grafting, a highly vascularized section of the fibula, with its associated muscle and skin flaps, are removed for implantation in other affected areas. (B) In the induced membrane technique, an autograft is placed inside a highly vascularized tissue envelope formed around a temporary bone cement spacer. (C) A general schematic of an Ilizarov apparatus around a tibial defect. Distraction osteogenesis utilizes several mechanical devices such as this one to repair long bone defects.
Figure 4
Figure 4
Integration of BTE strategies into a vascularized construct.
Figure 5
Figure 5
Levels of graft integration into the host body: (A) osseointegration, (B) vascular anastomosis, (C) vascular scaffold integration.
See this image and copyright information in PMC

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