Vascularization in Bone Tissue Engineering: Physiology, Current Strategies, Major Hurdles and Future Challenges

Santos, Marina I.; Reis, Rui L.

doi:10.1002/mabi.200900107

Cited by 382 publications

(282 citation statements)

References 202 publications

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“…To date, cell-based bone tissue engineering applications have generally focused on the direct osteogenic priming of mesenchymal stem cell (MSC) seeded scaffolds in a process resembling intramembranous ossification [3]. This approach however, has been hampered by insufficient vascularization of the graft following in vivo implantation, thus preventing the necessary delivery of oxygen and nutrients required to ensure cell survival [4]. For example, in vitro osteogenic priming of engineered constructs has been shown to occlude the pores of a scaffold with calcified matrix, resulting in the development of a necrotic core upon implantation into bony defects [5].…”

Section: Introductionmentioning

confidence: 99%

Engineering cartilage or endochondral bone: A comparison of different naturally derived hydrogels

et al. 2015

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Cartilaginous tissues engineered using mesenchymal stem cells (MSCs) have been shown to generate bone in vivo by executing an endochondral program. This may hinder the use of MSCs for articular cartilage regeneration, but opens the possibility of using engineered cartilaginous tissues for large bone defect repair. Hydrogels may be an attractive tool in the scaling-up of such tissue engineered grafts for endochondral bone regeneration. In this study, we compared the capacity of different naturally derived hydrogels (alginate, chitosan, and fibrin) to support chondrogenesis and hypertrophy of MSCs in vitro and endochondral ossification in vivo. In vitro, alginate and chitosan constructs accumulated the highest levels of sGAG, with chitosan constructs synthesising the highest levels of collagen. Alginate and fibrin constructs supported the greatest degree of calcium accumulation, though only fibrin constructs calcified homogenously. In vivo, chitosan constructs facilitated neither vascularization nor endochondral ossification, and also retained the greatest amount of sGAG, suggesting it to be a more suitable material for the engineering of articular cartilage.Both alginate and fibrin constructs facilitated vascularization and endochondral bone formation as well as the development of a bone marrow environment. Alginate constructs accumulated significantly more mineral and supported greater bone formation in central regions of the engineered tissue. In conclusion, this study demonstrates the capacity of chitosan hydrogels to promote and better maintain a chondrogenic phenotype in MSCs and highlights the potential of utilizing alginate hydrogels for MSC-based endochondral bone tissue engineering applications.

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Section: Introductionmentioning

confidence: 99%

Engineering cartilage or endochondral bone: A comparison of different naturally derived hydrogels

et al. 2015

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“…This study demonstrates the regulatory role of forces in angiogenesis and their capacities in vessel structure manipulation, which can be exploited to improve scaffolds for tissue repair. T echniques to generate vascularized tissues bear significant clinical value in regenerative medicine because they ensure sufficient oxygen and nutrient supply within the host tissue, cardinal to transplant integration and survival (1)(2)(3)(4)(5)(6)(7). Recent works have attempted to optimize blood vessel network properties, such as geometry, maturity, and stability, by supplementing cultures with biological factors (8), biomaterials (9), and geometrical constraints (10,11).…”

mentioning

confidence: 99%

Morphogenesis of 3D vascular networks is regulated by tensile forces

Rosenfeld

Landau

Shandalov

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Understanding the forces controlling vascular network properties and morphology can enhance in vitro tissue vascularization and graft integration prospects. This work assessed the effect of uniaxial cell-induced and externally applied tensile forces on the morphology of vascular networks formed within fibroblast and endothelial cell-embedded 3D polymeric constructs. Force intensity correlated with network quality, as verified by inhibition of force and of angiogenesis-related regulators. Tensile forces during vessel formation resulted in parallel vessel orientation under static stretching and diagonal orientation under cyclic stretching, supported by angiogenic factors secreted in response to each stretch protocol. Implantation of scaffolds bearing network orientations matching those of host abdominal muscle tissue improved graft integration and the mechanical properties of the implantation site, a critical factor in repair of defects in this area. This study demonstrates the regulatory role of forces in angiogenesis and their capacities in vessel structure manipulation, which can be exploited to improve scaffolds for tissue repair.

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“…Therefore, the neovascularization goes together with new-formed bone formation (Raines et al, 2010;Santos and Reis, 2010) and clinically, this point is of particular interest to enhance the primary and longterm fixation of implants (Davies, 2003;Broos and Sermon, 2004;Sakka and Coulthard, 2009). …”

Section: Discussionmentioning

confidence: 99%

Wave front migration of endothelial cells in a bone-implant interface

Khalil

Lorthois

Marcoux

et al. 2011

Journal of Biomechanics

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OATAO is an open access repository that collects the work of Toulouse researchers and makes it freely available over the web where possible. This is an author-deposited version published in : http://oatao.univ-toulouse.fr/ Eprints ID : 18179 a b s t r a c tThe neo-vascularization of the host site is crucial for the primary fixation and the long-term stability of the bone-implant interface. Our aim was to investigate the progression of endothelial cell population in the first weeks of healing. We proposed a theoretical reactive model to study the role of initial conditions, random motility, haptotaxis and chemotaxis in interactions with fibronectin factors and transforming angiogenic factors. The application of governing equations concerned a canine experimental implant and numerical experiments based upon statistical designs of experiments supported the discussion.We found that chemotaxis due to transforming angiogenic factors was attracting endothelial cells present into the host bone. Haptotaxis conditioned by fibronectin factors favored cells adhesion to the host bone. The combination of diffusive and reactive effects nourished the wave front migration of endothelial cells from the host bone towards the implant. Angiogenesis goes together with new-formed bone formation in clinics, so the similarity of distribution patterns of mineralized tissue observed invivo and the spatio-temporal concentration of endothelial cells predicted by the model, tended to support the reliability of our theoretical approach.

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Vascularization in Bone Tissue Engineering: Physiology, Current Strategies, Major Hurdles and Future Challenges

Cited by 382 publications

References 202 publications

Engineering cartilage or endochondral bone: A comparison of different naturally derived hydrogels

Engineering cartilage or endochondral bone: A comparison of different naturally derived hydrogels

Morphogenesis of 3D vascular networks is regulated by tensile forces

Wave front migration of endothelial cells in a bone-implant interface

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