Sustained delivery of vascular endothelial growth factor from mesoporous calcium‐deficient hydroxyapatite microparticles promotes in vitro angiogenesis and osteogenesis

Abstract

Promoting the growth of blood vessels within engineered tissues remains one of the main challenge in bone tissue engineering. One way to improve angiogenesis is the use of vascular endothelial growth factor (VEGF) as it holds the ability to increase the formation of a vascular network. In the present study, collagen scaffolds with VEGF‐releasing hydroxyapatite particles were fabricated, in order to engineer a material both capable of presenting an osteoconductive surface and delivering an angiogenic growth factor in a localized and sustained manner, in order to enhance osteogenesis as well as angiogenesis. To this end, we developed microparticles and characterize their size, chemical properties and Ca/P ratio to validate the formation of hydroxyapatite. We then evaluated the osteogenic potential of HAp when cultured with mesenchymal stem cells and compare it to commercially available hydroxyapatite (SBp). Finally, we characterized the encapsulation and release of VEGF in the HAp and assess the angiogenic potential of the VEGF‐HAp when cultured with endothelial cells. We demonstrated the successful fabrication of calcium deficient hydroxyapatite microparticles (CDHAp), with biological properties closer to the bone than stoichiometric, commercially available hydroxyapatite. This CDHAp exhibited a well‐defined 3D network of crystalline nanoplates forming mesoporous and hollow structures. The high specific area created by those structures enabled the loading of VEGF with high efficiency when compared to the loading efficiency of SBp. Furthermore, their biological performances were evaluated in vitro. Our results indicate that VEGF‐CDHAp can be used to improve both osteogenesis and angiogenesis in vitro.

Bone Regeneration and Oxidative Stress: An Updated Overview

“…Biomaterials and scaffolds can promote healthy tissue formation and are sought in fields such as bone regeneration [ 16 ]. Successful approaches orient towards materials that present a good biomimetic property and are bioactive to obtain similar structural features compared to the original extracellular matrix (ECM) [ 17 , 18 , 19 ].…”

Vascularization Strategies in Bone Tissue Engineering

“…A great variety of natural [ 41 , 42 , 43 ], semi-synthetic [ 44 , 45 ], and synthetic [ 46 , 47 , 48 , 49 ] hydrogels have been used during the past decade for the release of a great variety of different GFs in order to improve neovascularization in BTE. From these studies, it became clear that an effective angiogenic therapy is strictly dependent not only on the right GF or the right combination of different GFs, but also on a temporal and dose controlled release of the angiogenic GFs.…”

Influence of Biomimetically Mineralized Collagen Scaffolds on Bone Cell Proliferation and Immune Activation

“…In native bone tissue, collagen occurs in combination with a mineral component, formed by calcium phosphates, mainly in an apatite form (for a review, see [ 10 , 11 ]). Tissue engineers have therefore often used a combination of collagen with similar inorganic materials, such as hydroxyapatite (HAp) [ 18 , 19 , 20 ], tricalcium phosphate [ 21 ] or bioactive glass [ 22 ].…”

“…Dissolution products from composite bioglass–carbonate apatite–collagen scaffolds, containing calcium ions, soluble silicon species and phosphorus, promoted osteogenic differentiation in primary human osteoblasts, manifested by an increased expression of genes for osteopontin and osteocalcin [ 22 ]. Mineral particles within collagen-based scaffolds can also be utilized as carriers for the controlled delivery of various biologically active molecules, such as anti-osteoporotic drugs [ 18 ], bone morphogenetic protein-2 [ 19 ] and vascular endothelial growth factor [ 20 ].…”