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.

中文翻译：

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介孔缺钙羟基磷灰石微粒持续输送血管内皮生长因子促进体外血管生成和成骨

促进工程组织内血管的生长仍然是骨组织工程的主要挑战之一。改善血管生成的一种方法是使用血管内皮生长因子 (VEGF)，因为它具有增加血管网络形成的能力。在本研究中，制造了具有释放 VEGF 的羟基磷灰石颗粒的胶原支架，以设计一种既能呈现骨传导表面又能以局部和持续的方式提供血管生成生长因子的材料，以增强骨生成以及血管生成。为此，我们开发了微粒并表征了它们的尺寸、化学性质和 Ca/P 比，以验证羟基磷灰石的形成。然后，我们评估了 HAp 在与间充质干细胞一起培养时的成骨潜力，并将其与市售的羟基磷灰石 (SBp) 进行比较。最后，我们表征了 VEGF 在 HAp 中的包封和释放，并评估了与内皮细胞一起培养时 VEGF-HAp 的血管生成潜力。我们证明了缺钙羟基磷灰石微粒 (CDHAp) 的成功制造，其生物学特性比化学计量的市售羟基磷灰石更接近骨骼。该 CDHAp 表现出明确的 3D 晶体纳米板网络，形成中孔和中空结构。与 SBp 的负载效率相比，由这些结构产生的高比区域能够高效地负载 VEGF。此外，在体外评估了它们的生物学性能。