Angiogenesis in Calcium Phosphate Scaffolds by Inorganic Copper Ion Release

Abstract

Angiogenesis in a tissue-engineered device may be induced by incorporating growth factors (e.g., vascular endothelial growth factor [VEGF]), genetically modified cells, and=or vascular cells. It represents an important process during the formation and repair of tissue and is essential for nourishment and supply of reparative and immunological cells. Inorganic angiogenic factors, such as copper ions, are therefore of interest in the fields of regenerative medicine and tissue engineering due to their low cost, higher stability, and potentially greater safety compared with recombinant proteins or genetic engineering approaches. The purpose of this study was to compare tissue responses to 3D printed macroporous bioceramic scaffolds implanted in mice that had been loaded with either VEGF or copper sulfate. These factors were spatially localized at the end of a single macropore some 7 mm from the surface of the scaffold. Controls without angiogenic factors exhibited only poor tissue growth within the blocks; in contrast, low doses of copper sulfate led to the formation of microvessels oriented along the macropore axis. Further, wound tissue ingrowth was particularly sensitive to the quantity of copper sulfate and was enhanced at specific concentrations or in combination with VEGF. The potential to accelerate and guide angiogenesis and wound healing by copper ion release without the expense of inductive protein(s) is highly attractive in the area of tissue-engineered bone and offers significant future potential in the field of regenerative biomaterials.

MSC-seeded dense collagen scaffolds with a bolus dose of VEGF promote healing of large bone defects

“…Hydroxyapatite-tricalcium phosphate (HA-TCP), alone or in combination with autogenous bone, has been under investigation for more than three decades for this purpose (Rootare et al, 1978;Moore et al, 1987). More recent studies have focused primarily on the use of calcium and magnesium based scaffolds and cements for the controlled release of bioactive molecules, including antibiotics and anti-neoplastic agents, into the bone micro-environment (Barralet et al, 2009;Roohani-Esfahani et al, 2012;Soundrapandian et al, 2010). A major disadvantage of calcium phosphate based scaffolds is resistance to resorption by osteoclasts, unless they are pre-treated with an osteoclast activator such as RANK ligand (LeNihouannen et al, 2008), which has severely limited their clinical utility.…”

Prevascularization of a Gas-Foaming Macroporous Calcium Phosphate Cement Scaffold Via Coculture of Human Umbilical Vein Endothelial Cells and Osteoblasts

“…6,[11][12][13][14][15] However, a major limitation of bone tissue engineering is the difficulty to vascularize the construct. [16][17][18] When a scaffold is seeded with cells and implanted in vivo, only the cells within the proximity of 100-200 mm from a capillary can obtain an adequate supply of oxygen and nutrients to survive. 16,17 Insufficient vascularization will cause nutrient deficiencies and hypoxia of the seeded cells, resulting in decreased tissue function and cell death at the core.…”

Up-to-Date Knowledge and Outlooks for the Use of Metallic Biomaterials: Review Paper

“…Actually, there is a continuous growth in medical ield of the use of metal ions in RM and tissue engineering, with a special atention concerned to their therapeutic properties. However, the possible toxicity of metal ions in case of their eventually local release has to be carefully considered, when exploiting them [67][68][69][70].…”