Interplay between self‐assembled structure of bone morphogenetic protein‐2 (BMP‐2) and osteoblast functions in three‐dimensional titanium alloy scaffolds: Stimulation of osteogenic activity

Abstract

Three-dimensional cellular scaffolds are receiving significant attention in bone tissue engineering to treat segmental bone defects. However, there are indications of lack of significant osteoinductive ability of three-dimensional cellular scaffolds. In this regard, the objective of the study is to elucidate the interplay between bone morphogenetic protein (BMP-2) and osteoblast functions on 3D mesh structures with different porosities and pore size that were fabricated by electron beam melting. Self-assembled dendritic microstructure with interconnected cellular-type morphology of BMP-2 on 3D scaffolds stimulated osteoblast functions including adhesion, proliferation, and mineralization, with prominent effect on 2-mm mesh. Furthermore, immunofluorescence studies demonstrated higher density and viability of osteoblasts on lower porosity mesh structure (2 mm) as compared to 3- and 4-mm mesh structures. Enhanced filopodia cellular extensions with extensive cell spreading was observed on BMP-2 treated mesh structures, a behavior that is attributed to the unique self-assembled structure of BMP-2 that effectively communicates with the cells. The study underscores the potential of BMP-2 in imparting osteoinductive capability to the 3D printed scaffolds.

Fabrication of open-cellular (porous) titanium alloy implants: osseointegration, vascularization and preliminary human trials

“…Inter-cellular interaction in porous implant structures provides a pathway for cell communication and differentiated phenotype malfunction, leading to colonization of the entire structure. Phenotype maturity was also expressed by calcium mineralization (mineralized ECal) secreted by cells along the struts and ligaments of the porous structures revealed in previous studies using a differentiation assay [11].…”

“…These appliances, either variously configured reticulated mesh structures or foam structures, also allow for the incorporation of antibiotic agents [2,5] along with growth factors, signaling molecules, and specific cells promoting oxygen and nutrient exchange which facilitates efficient cell seeding and extracellular matrix (ECM) production; including tissue regeneration and vascularization [6][7][8][9]. Growth factors are proteins which serve as signaling agents for specific cell function such as bone morphogenetic proteins (BMPs) and vascular (endothelial) cell growth factor (VEGF) [10][11]. Kang et al [12] have also recently noted that, "a challenge for tissue engineering is producing 3D vascularized cellular constructs of clinically relevant size, shape and structural integrity".…”

Advancements in three-dimensional titanium alloy mesh scaffolds fabricated by electron beam melting for biomedical devices: mechanical and biological aspects

“…The bioactivity of the surface was improved and the modified surface was expected to enhance the fixation of the implant with the surrounding bone and improve the long-term stability [127,128].…”

“…Incorporation of other drugs such as dexamethasone, hydrogels, simvastatin, antimicrobial agents, and VEGF has also been explored [127][128][129][130].…”

“…The potential role of topography of the material in determining the molecular assembly of BMP-2 and subsequent osteoblast functions indicated a significant difference in organization and assembly of protein [127]. It was proposed that 300 µm pore size mesh structure with interconnected porous architecture was superior to mesh structures with 600 µm and 900 µm pore size respectively, in terms of cell proliferation and mineralization.…”