Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2012 Oct;18(5):363-82.
doi: 10.1089/ten.TEB.2012.0012. Epub 2012 Sep 4.

Vascularized bone tissue engineering: approaches for potential improvement

Lonnissa H Nguyen  1 , Nasim Annabi, Mehdi Nikkhah, Hojae Bae, Loïc Binan, Sangwon Park, Yunqing Kang, Yunzhi Yang, Ali Khademhosseini
Affiliations
Review

Vascularized bone tissue engineering: approaches for potential improvement

Lonnissa H Nguyen et al. Tissue Eng Part B Rev. 2012 Oct.

Abstract

Significant advances have been made in bone tissue engineering (TE) in the past decade. However, classical bone TE strategies have been hampered mainly due to the lack of vascularization within the engineered bone constructs, resulting in poor implant survival and integration. In an effort toward clinical success of engineered constructs, new TE concepts have arisen to develop bone substitutes that potentially mimic native bone tissue structure and function. Large tissue replacements have failed in the past due to the slow penetration of the host vasculature, leading to necrosis at the central region of the engineered tissues. For this reason, multiple microscale strategies have been developed to induce and incorporate vascular networks within engineered bone constructs before implantation in order to achieve successful integration with the host tissue. Previous attempts to engineer vascularized bone tissue only focused on the effect of a single component among the three main components of TE (scaffold, cells, or signaling cues) and have only achieved limited success. However, with efforts to improve the engineered bone tissue substitutes, bone TE approaches have become more complex by combining multiple strategies simultaneously. The driving force behind combining various TE strategies is to produce bone replacements that more closely recapitulate human physiology. Here, we review and discuss the limitations of current bone TE approaches and possible strategies to improve vascularization in bone tissue substitutes.

PubMed Disclaimer

Figures

FIG. 1.
FIG. 1.
Bone anatomy (Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings). Color images available online at www.liebertpub.com/teb
FIG. 2.
FIG. 2.
Various strategies to enhance vascularization in bone tissue engineering (TE). MSCs, mesenchymal stem cells; EC, endothelial cells; BMP, bone morphogenetic protein; VEGF, vascular endothelial growth factor. Color images available online at www.liebertpub.com/teb
FIG. 3.
FIG. 3.
Digital image (A) and two-dimensional micro-CT image (B) of calcium phosphate-graded scaffolds fabricated by using templating-casting method. The internal part of scaffold contained pores between 350 to 500 μm in diameter and the external zone contained pores between 600 and 800 μm (adapted with permission from Ref.). (C) Histology images of bone morphogenetic protein (BMP)-2-induced ectopic bone formation in porous scaffold one month after implantation in nude mouse, demonstrating that the pores of scaffold were filled with newly formed bone, which is observed as the violet stain. (D) Radiography and (E) longitudinal micro-CT images of scaffold-aided bone healing at one month after implantation in a 1.5-cm bone defect in rabbit. (F) Longitudinal HE-stained histological image of a nondecalcified scaffold-bone sample. Arrows indicate the scaffold. Color images available online at www.liebertpub.com/teb
FIG. 4.
FIG. 4.
SEM images of previously microfabricated platforms for bone TE applications. (A) Microfabricated PDMS channels; (B) three-dimensional scaffold fabricated with poly (propylene fumarate); (C) micropatterned polyethylene glycol (PEG) hydrogel on flat silicon surfaces; and (D) microfluidic network fabricated in polydimethylsiloxane (PDMS) (adapted with permission from Refs.–,).
FIG. 5.
FIG. 5.
(A) Top and cross-sectional confocal images of the actin filaments and tubule formation in endothelial cells (ECs) on PEG hydrogels patterned with RGDS and vascular endothelial growth factor. (B) Immunofluorescence images of ECs forming branched tubules using a micromolding technique. Actin filaments are stained in red, nuclei is stained in blue, and β-catenin is stained in green. (C) Microfluidic network fabricated in agarose hydrogels. (D) Highly branched microfluidic network fabricated in PDMS for vascularization applications (adapted with permission from Refs.,,,). Color images available online at www.liebertpub.com/teb
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Salgado A.J. Coutinho O.P. Reis R.L. Bone tissue engineering: state of the art and future trends. Macromol Biosci. 2004;4:743. - PubMed
    1. Goldstein S.A. Tissue engineering: functional assessment and clinical outcome. Ann N Y Acad Sci. 2002;961:183. - PubMed
    1. Sikavitsas V.I. Temenoff J.S. Mikos A.G. Biomaterials and bone mechanotransduction. Biomaterials. 2001;22:2581. - PubMed
    1. Turner C.H. Wang T. Burr D.B. Shear strength and fatigue properties of human cortical bone determined from pure shear tests. Calcif Tissue Int. 2001;69:373. - PubMed
    1. Hillier M.L. Bell L.S. Differentiating human bone from animal bone: a review of histological methods. J Forensic Sci. 2007;52:249. - PubMed

Publication types

LinkOut - more resources