Engineering Porous β-Tricalcium Phosphate (β-TCP) Scaffolds with Multiple Channels to Promote Cell Migration, Proliferation, and Angiogenesis

Abstract

Inadequate oxygen and nutrient diffusion in a porous scaffold often resulted in insufficient formation of branched vasculatures, which hindered bone regeneration. In this study, interconnected porous β-tricalcium phosphate (β-TCP) scaffolds with different geometric designs of channels were fabricated and compared to discover the functionality of structure on facilitating nutrient diffusion for angiogenesis. In vitro fluid transportation and degradation of the scaffolds were performed. Cell infiltration, migration, and proliferation of human umbilical vein endothelial cells (HUVECs) on the scaffolds were carried out under both static and dynamic culture conditions. A computational simulation model and a series of immunofluorescent staining were implemented to understand the mechanism of cell behavior in response to different types of scaffolds. Results showed that geometry with multiple channels significantly accelerated the release of Ca 2+ and increased the fluid diffusion efficiency. Moreover, multiple channels promoted HUVECs' infiltration and migration in vitro. The ex vivo implantation results showed that the channels promoted cells from the rats' calvarial bone explants to infiltrate into the implanted scaffold. Multiple channels also stimulated HUVECs' proliferation prominently at both static and dynamic culturing conditions. The expression of both cell migration-related protein α5 and angiogenesis-related protein CD31 on multiplechanneled scaffolds was upregulated compared to that on the other two types of scaffolds, implying that multiple channels reinforced cell migration and angiogenesis. All the findings suggested that the geometric design of multiple channels in the porous β-TCP scaffold has promising potential to promote cell infiltration, migration, and further vascularization when implanted in vivo.

The Potential Selective Cytotoxicity of Poly (L- Lactic Acid)-Based Scaffolds Functionalized with Nanohydroxyapatite and Europium (III) Ions toward Osteosarcoma Cells

“…Modern regenerative medicine is undeniably one of the fastest developing scientific fields, which gives a great hope to the patients that suffer from serious diseases or injuries. Current efforts are put into developing novel composites tailored to meet the great needs of regenerative medicine and oncology [44,45]. The opportunity to design alternative treatment methods gives a real chance to restore damaged tissues and prolong patients’ healthy life.…”

Effects of Macro-/Micro-Channels on Vascularization and Immune Response of Tissue Engineering Scaffolds

“…The mechanically removable template method includes the use of templates or removable rods to create macro-channels. This method has shown the potential to create channels in the scaffolds and provide structure for cells within the channels [ 47 , 48 ]. Secondly, the use of a removable template spacer is instrumental in the sacrificial template method.…”

“…In addition to the method of creating channels, the number of channels within a scaffold and the sizes of the channels may influence the effectiveness of the scaffold. If the incorporation of macro-/micro-channels within a scaffold increases vascularization within the scaffolds and allows oxygen and other nutrients to be distributed equally throughout the scaffold, this will bring promise in regenerating even larger tissues [ 48 ].…”

Bi-directional regulation functions of lanthanum-substituted layered double hydroxide nanohybrid scaffolds via activating osteogenesis and inhibiting osteoclastogenesis for osteoporotic bone regeneration

“…Traditional bone repair materials such as β-tricalcium phosphate and hydroxyapatite, showing similar chemical elements to bone minerals, exhibit desirable cytocompatibility and osteoconductivity 15 - 17 . However, they lack sufficient abilities to activate osteogenesis and inhibit osteoclastogenesis for osteoporotic bone regeneration 15 - 17 . Upon to now, layered double hydroxide (LDH, [M 1- x 2+ N x 3+ (OH) 2 ] x + [A x/n n- ] x- ·m H 2 O) have been employed for bone repair application 18 - 20 .…”