An Intrinsic Angiogenesis Approach and Varying Bioceramic Scaffold Architecture Affect Blood Vessel Formation in Bone Tissue Engineering In Vivo

Article Preview

Abstract:

Early establishment of angiogenesis is critical for bone tissue engineering. Recently, a technique was introduced, which is based on the idea of using axial vascularization of the host tissues in engineered grafts, namely the “intrinsic angiogenesis chamber” technique, which utilizes an artery and a vein to construct an AV-Bundle. The aim of this study was to evaluate the effect of varying scaffold architecture of calcium alkali orthophosphate scaffolds (CAOP), resulting from two different fabrication procedures, namely 3D printing (RP) or a Schwarzwalder-Somers replica technique (SSM), on angiogenesis in vivo when combining a microvascular technique with bioceramic scaffolds colonized with stem cells for bone tissue engineering. 32 adult female Wistar rats, in which critical size segmental discontinuity defects 6 mm in length were created in the left femur, were divided into 4 groups, group 1 received a RP scaffold colonized with rat stem cells after 7d of dynamic cell culture and an AV-Bundle (AVB), group 2 a SSM scaffold with rat stem cells after 7d of dynamic cell culture and an AVB, group 3 a RP control scaffold (without cells and AVB), group 4 a SSM control scaffold (without cells and AVB). After 3 and 6 months, angiomicro-CT after perfusion with a contrast agent, image reconstruction, histomorphometric and immunohistochemical analysis utilizing antibodies to collagen IV, vWF and CD-31 were performed. At 6 months, a statistically significant higher blood vessel volume%, blood vessel surface/volume, blood vessel thickness, blood vessel density and blood vessel linear density was observed with RP scaffolds with cells and AVB than with the other groups. At 6 mths, RP with cells and AVB displayed the highest expression of collagen IV (score 2.75), CD31 (score 2.75) and vWF (score 2.6), which is indicative of highly dense blood vessels. Both angio-CT and immunohistochemical analysis demonstrated that AVB is an efficient technique for achieving scaffold vascularization in critical size segmental defects after 3 and 6 months of implantation.

You might also be interested in these eBooks

Info:

* - Corresponding Author

[1] D. Han, X. Guan, J. Wang, J. Wei, Q. Li, Rabbit tibial periosteum and saphenous arteriovenous vascular bundle as an in vivo bioreactor to construct vascularized tissue-engineered bone: a feasibility study, Artif Organs. 38 (2014) 167-174.

DOI: 10.1111/aor.12124

Google Scholar

[2] U. Kneser, E. Polykandriotis, J. Ohnolz, K. Heidner , L. Grabinger , S. Euler, K.U. Amann, A. Hess, K. Brune, P. Greil, M. Stürzl, R.E. Horch RE. Engineering of vascularized transplantable bone tissues: Induction of axial vascularization in an osteoconductive matrix using an arteriovenous loop, Tissue Eng. 12 (2006).

DOI: 10.1089/ten.2006.12.1721

Google Scholar

[3] Z. Lokmic, G.M. Mitchell. Engineering the microcirculation. Tissue Eng Part B, 14 (2008) 87-103 Review.

Google Scholar

[4] H. Fan, X. Zeng , X. Wang, R. Zhu, G. Pei. Efficacy of prevascularization for segmental bone defect repair using β-tricalcium phosphate scaffold in rhesus monkey, Biomaterials 35 (2014) 7407-7415.

DOI: 10.1016/j.biomaterials.2014.05.035

Google Scholar

[5] O.O. Erol, M. Spira. New capillary bed formation with a surgically constructed arteriovenous fistula, Surg Forum. 30 (1979)530.

DOI: 10.1097/00006534-198007000-00021

Google Scholar

[6] L.L. Ren, D.Y. Ma, X. Feng, T.Q. Mao, Y.P. Liu, Y. Ding: A novel strategy for prefabrication of large and axially vascularized tissue engineered bone by using an arteriovenous loop, Med Hypotheses. 71 (2008) 737-740.

DOI: 10.1016/j.mehy.2008.06.032

Google Scholar

[7] M. Kampschulte, G.A. Krombach, D.C. Richards, J. Sender, K.S. Lips, U. Thormann, El T. Khassawna, S. Ray, V. Alt, A.C. Langheinrich. Neovascularization of osteoporotic metaphyseal bone defects: A morphometric micro-CT study, Microvasc Res. 105 (2015).

DOI: 10.1016/j.mvr.2015.10.005

Google Scholar

[8] C. Knabe, B. Kraska, C. Koch1, U. Gross, H. Zreiqat, M. Stiller. A method for immunohistochemical detection of osteogenic markers in undecalcified bone sections, Biotechnic & Histochemistry. 81 (2006) 31-39.

DOI: 10.1080/10520290600725474

Google Scholar

[9] J.F. De Oliveira, P.F. De Aguiar, A.M. Rossi, G.A. Soares. Effect of process parameters on the characteristics of porous calcium phosphate ceramics for bone tissue scaffolds, Artif Organs 27 (2003) 406-411.

DOI: 10.1046/j.1525-1594.2003.07247.x

Google Scholar

[10] M. Navarro, S. del Valle, S. Martinez, S. Zeppetelli, L. Ambrosio, J.A. Planell, M.P. Ginebra. New macroporous calcium phosphate glass ceramic for guided bone regeneration, Biomaterials. 25 (2004) 4233-4241.

DOI: 10.1016/j.biomaterials.2003.11.012

Google Scholar

[11] R.E. Unger, A. Sartoris, K. Peters, A. Motta, C. Migliaresi, M. Kunkel, U. Bulnheim, J. Rychly, C.J. Kirkpatrick. Tissue-like self-assembly in cocultures of endothelial cells and osteoblasts and the formation of microcapillary-like structures on three-dimensional porous biomaterials, Biomaterials. 28 (2007).

DOI: 10.1016/j.biomaterials.2007.05.032

Google Scholar

[12] F. Bai, Z. Wang, J. Lu, J. Liu, G. Chen, R. Lv, J. Wang, K. Lin, J. Zhang, X. Huang. The correlation between the internal structure and vascularization ofncontrollable porous bioceramic materials in vivo: a quantitative study, Tissue Eng Part A. 16 (2010).

DOI: 10.1089/ten.tea.2010.0148

Google Scholar

[13] E. Polykandriotis , S. Euler, A. Arkudas, G. Pryymachuk, J.P. Beier, P. Greil, A. Dragu, A. Lametschwandtner, U. Kneser, R.E. Horch. Regression and persistence: remodelling in a tissue engineered axial vascular assembly, J. Cell Mol Med. 13 (2009).

DOI: 10.1111/j.1582-4934.2009.00828.x

Google Scholar

[14] R. Costa-Almeida, P.L. Granja, R. Soares, S.G. Guerreiro . Cellular strategies to promote vascularisation in tissue engineering applications, Eur. Cell Mater. 28 (2014) 51-66.

DOI: 10.22203/ecm.v028a05

Google Scholar