Critical bone defects caused by trauma, tumor removal, or congenital conditions pose significant treatment challenges due to the high likelihood of graft failure, often resulting from poor blood supply. To address this problem, researchers have developed innovative 3D-printed scaffolds made from polylactic acid and calcium phosphate, which help promote blood vessel formation, improving the healing and regeneration of bone tissue.

Bone is a highly vascularized tissue, and the connection between angiogenesis, or the formation of blood vessels, and bone healing has long been recognized. Several studies have shown that impaired bone healing can occur when angiogenesis is lacking or insufficient. Traditional treatment methods, such as grafting, often lead to complications due to the inability of the implant to integrate properly, as they suffer from inadequate blood supply, resulting in necrosis. To solve this issue, researchers at the Institute for Bioengineering of Catalonia (IBEC, Barcelona, Spain) have utilized 3D bioprinting to create polylactic acid and calcium phosphate-based glass scaffolds that support angiogenesis and the maturation of blood vessels. Bone tissue is composed of both a non-mineralized organic component (primarily collagen) and a mineralized inorganic part (mainly hydroxyapatite). The researchers' approach involved using calcium phosphate (CaP) glass scaffolds to enhance the properties of polylactic acid (PLA), thereby producing a material that meets the chemical, mechanical, and biological requirements for bone tissue.

The new PLA-CaP scaffolds support adequate vascularization, which not only aids in tissue healing but also promotes efficient bone regeneration, potentially reducing or eliminating bone scarring. To build these scaffolds, the researchers employed 3D printing, allowing for precise control over scaffold geometry, porosity, and surface characteristics. In vitro tests revealed that the 3D-printed scaffolds supported the proliferation of human mesenchymal stem cells and stimulated the secretion of vascular endothelial growth factor (VEGF), a key protein that promotes blood vessel formation. Additionally, the scaffolds maintained calcium ion release at physiological levels, which is essential for vascularization. In vivo testing using a subcutaneous mouse model also yielded promising results. Within just one week of implantation, the scaffolds showed good integration with significant blood vessel infiltration.

The PLA-CaP scaffolds proved particularly effective, with increased vessel maturation observed after four weeks and no signs of vascular regression. Analysis of the blood vessels showed that the vessel walls, initially thin, thickened and stabilized over time, demonstrating that the scaffolds not only support initial blood vessel growth but also provide a favorable environment for long-term vascularization—an essential factor for successful bone regeneration. This advanced scaffold development highlights the synergistic benefits of combining 3D printing technology with bioactive materials like calcium-releasing particles. The architecture of the PLA-CaP scaffolds enhances both vascularization and osteogenesis, opening the door for more effective bone healing strategies and potentially reducing graft failure rates.

“We believe that our 3D printed scaffolds could revolutionize the way we approach bone regeneration,” said Celia Ximenes-Carballo, first author of the study. “By enhancing vascularization, we can significantly improve healing outcomes and reduce the chances of complications associated with traditional grafting methods.” 

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