Biomaterial-mediated strategies targeting vascularization for bone repair

García, José R.; Garcı́a, Andrés J.

doi:10.1007/s13346-015-0236-0

Cited by 77 publications

(70 citation statements)

References 187 publications

(171 reference statements)

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“…Vascularization is a crucial factor in bone development as well as the repair of bone defects. [1][2][3] In the developing skeleton, long bones are formed through endochondral ossification, which involves the invasion and sprouting of blood vessels into the intermediate cartilage tissue followed by osteoprogenitor cell migration and mineralization of the cartilaginous anlage. 4 Blocking infiltration of blood vessels into cartilage causes enlarged hypertrophic zones associated with incomplete and delayed onset of ossification and suboptimal bone formation.…”

Section: Introductionmentioning

confidence: 99%

Integrin‐specific hydrogels functionalized with VEGF for vascularization and bone regeneration of critical‐size bone defects

García

Clark

Garcı́a

2016

J Biomedical Materials Res

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101

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Vascularization of bone defects is considered a crucial component to the successful regeneration of large bone defects. Although vascular endothelial growth factor (VEGF) has been delivered to critical-size bone defect models to augment blood vessel infiltration into the defect area, its potential to increase bone repair remains ambiguous. In this study, we investigated whether integrin-specific biomaterials modulate the effects of VEGF on bone regeneration. We engineered protease-degradable, VEGF-loaded polyethylene glycol (PEG) hydrogels functionalized with either a triple-helical, α2β1 integrin-specific peptide (GFOGER) or an αvβ3 integrin-targeting peptide (RGD). Covalent incorporation of VEGF into the PEG hydrogel allowed for protease degradation-dependent release of the protein while maintaining VEGF bioactivity. When applied to critical-size segmental defects in the murine radius, GFOGER-functionalized VEGF-free hydrogels exhibited significantly increased vascular volume and density and resulted in a larger number of thicker blood vessels compared to RGD-functionalized VEGF-free hydrogels. VEGF-loaded RGD hydrogels increased vascularization compared to VEGF-free RGD hydrogels, but the levels of vascularization for these VEGF-containing RGD hydrogels were similar to those of VEGF-free GFOGER hydrogels. VEGF transiently increased bone regeneration in RGD hydrogels but had no effect at later time points. In GFOGER hydrogels, VEGF did not show an effect on bone regeneration. However, VEGF-free GFOGER hydrogels resulted in increased bone regeneration compared to VEGF-free RGD hydrogels. These findings demonstrate the importance of integrin-specificity in engineering constructs for vascularization and associated bone regeneration.

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Section: Introductionmentioning

confidence: 99%

Integrin‐specific hydrogels functionalized with VEGF for vascularization and bone regeneration of critical‐size bone defects

García

Clark

Garcı́a

2016

J Biomedical Materials Res

Self Cite

101

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“…Vascularization is a critical step for bone regeneration. [ 31 ] Blood vessels, associated with bone (either lamellar, as Haversian canals, or woven) and non‐mineralized tissue, were present throughout all zones, regardless of the architecture. The size of these vessels, which is an indicator of vessel stability and vascularization potential of the scaffolds, [ 32 ] showed a decreasing trend from zone 1 to zone 3 for both architectures, albeit this difference was not statistically significant.…”

Section: Discussionmentioning

confidence: 99%

Orthotopic Bone Regeneration within 3D Printed Bioceramic Scaffolds with Region‐Dependent Porosity Gradients in an Equine Model

Diloksumpan

Bolaños

Cokelaere

et al. 2020

Adv Healthcare Materials

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The clinical translation of three-dimensionally printed bioceramic scaffolds with tailored architectures holds great promise toward the regeneration of bone to heal critical-size defects. Herein, the long-term in vivo performance of printed hydrogel-ceramic composites made of methacrylatedoligocaprolactone-poloxamer and low-temperature self-setting calciumphosphates is assessed in a large animal model. Scaffolds printed with different internal architectures, displaying either a designed porosity gradient or a constant pore distribution, are implanted in equine tuber coxae critical size defects. Bone ingrowth is challenged and facilitated only from one direction via encasing the bioceramic in a polycaprolactone shell. After 7 months, total new bone volume and scaffold degradation are significantly greater in structures with constant porosity. Interestingly, gradient scaffolds show lower extent of remodeling and regeneration even in areas having the same porosity as the constant scaffolds. Low regeneration in distal regions from the interface with native bone impairs ossification in proximal regions of the construct, suggesting that anisotropic architectures modulate the cross-talk between distant cells within critical-size defects. The study provides key information on how engineered architectural patterns impact osteoregeneration in vivo, and also indicates the equine tuber coxae as promising orthotopic model for studying materials stimulating bone formation.

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“…Providing nutrients and oxygen by means of a sufficient and rapid vascularization is at the heart of any successful attempts to grow more complex and larger tissueengineered substitutes such as bone, muscle, fat and solid organs. 14,15 Intrinsic vascularization offers the potential for larger constructs to develop by progressive tissue growth commensurate with its expanding blood supply. One design is the in vivo implantation into a chamber of a vascular pedicle with or without a cell seeded scaffold.…”

Section: 13mentioning

confidence: 99%

Tissue Engineering by Intrinsic Vascularization in an <em>In Vivo</em> Tissue Engineering Chamber

Zhan

Marré

Mitchell

et al. 2016

JoVE

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In reconstructive surgery, there is a clinical need for an alternative to the current methods of autologous reconstruction which are complex, costly and trade one defect for another. Tissue engineering holds the promise to address this increasing demand. However, most tissue engineering strategies fail to generate stable and functional tissue substitutes because of poor vascularization. This paper focuses on an in vivo tissue engineering chamber model of intrinsic vascularization where a perfused artery and a vein either as an arteriovenous loop or a flow-through pedicle configuration is directed inside a protected hollow chamber. In this chamber-based system angiogenic sprouting occurs from the arteriovenous vessels and this system attracts ischemic and inflammatory driven endogenous cell migration which gradually fills the chamber space with fibro-vascular tissue. Exogenous cell/matrix implantation at the time of chamber construction enhances cell survival and determines specificity of the engineered tissues which develop. Our studies have shown that this chamber model can successfully generate different tissues such as fat, cardiac muscle, liver and others. However, modifications and refinements are required to ensure target tissue formation is consistent and reproducible. This article describes a standardized protocol for the fabrication of two different vascularized tissue engineering chamber models in vivo.

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Biomaterial-mediated strategies targeting vascularization for bone repair

Cited by 77 publications

References 187 publications

Integrin‐specific hydrogels functionalized with VEGF for vascularization and bone regeneration of critical‐size bone defects

Integrin‐specific hydrogels functionalized with VEGF for vascularization and bone regeneration of critical‐size bone defects

Orthotopic Bone Regeneration within 3D Printed Bioceramic Scaffolds with Region‐Dependent Porosity Gradients in an Equine Model

Tissue Engineering by Intrinsic Vascularization in an <em>In Vivo</em> Tissue Engineering Chamber

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