Hierarchical surface roughness of titanium and titanium alloy implants plays an important role in osseointegration. In vitro and in vivo studies show greater osteoblast differentiation and bone formation when implants have submicron-scale textured surfaces. In this study, we tested the potential benefit of combining a submicron-scale textured surface with three-dimensional (3D) structure on osteoblast differentiation and the involvement of an integrin-driven mechanism. 3D titanium scaffolds were made using orderly oriented titanium meshes and microroughness was added to the wire surface by acid-etching. MG63 and human osteoblasts were seeded on 3D scaffolds and 2D surfaces with or without acid etching. At confluence, increased osteocalcin, vascular endothelial growth factor, osteoprotegerin (OPG), and alkaline phosphatase (ALP) activity were observed in MG63 and human osteoblasts on 3D scaffolds in comparison to 2D surfaces at the protein level, indicating enhanced osteoblast differentiation. To further investigate the mechanism of osteoblast-3D scaffold interaction, the role of integrin α2β1 was examined. The results showed β1 and α2β1 integrin silencing abolished the increase in osteoblastic differentiation markers on 3D scaffolds. Time course studies showed osteoblasts matured faster in the 3D environment in the early stage of culture, while as cells proliferated, the maturation slowed down to a comparative level as 2D surfaces. After 12 days of postconfluent culture, osteoblasts on 3D scaffolds showed a second-phase increase in ALP activity. This study shows that osteoblastic differentiation is improved on 3D scaffolds with submicron-scale texture and is mediated by integrin α2β1. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1907–1918, 2015.

Synovium-derived mesenchymal stem cells (SMSC) have been studied for over a decade since first being successfully isolated in 2001. These cells demonstrate the most promising therapeutic efficacy for musculoskeletal regeneration of the MSC family, particularly for cartilage regeneration. However, the mobilization and transfer of MSCs to defective or damaged tissues and organs in vivo with high accuracy and efficiency has been a major problem in tissue engineering (TE). In the present study, we identified a seven amino acid peptide sequence [SMSCs-affinity peptide (LTHPRWP; L7)] through phage display technology that has a high specific affinity to SMSCs. Our analysis suggested that L7 efficiently and specifically interacted with SMSCs without any species specificity. Thereafter, L7 was covalently conjugated onto both polycaprolactone (PCL) electrospun meshes and human decalcified bone scaffolds (hDBSc) to investigate its TE applications. After 24 h coculture with human SMSCs (hSMSCs), L7-conjugated PCL electrospun meshes had significantly more adherent hSMSCs than the control group, and the cells expanded well. Similar results were obtained using hDBSs. These results suggest that the novel L7 peptide sequence has a high specific affinity to SMSCs. Covalently conjugating this peptide to either artificial polymer material (PCL mesh) or natural material (hDBS) significantly enhances the adhesion of SMSCs. This method is applicable to a wide range of potential SMSC-based TE applications, particularly to cartilage regeneration, via surface modification on various type of materials. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 318–329, 2015.

Ceramic-derived materials have shown enhanced osteogenic potential for bone tissue engineering applications. Silica is the major component of bioglass, and titania, the oxide complex of titanium, has been found to enhance osteoblast differentiation. In this study, three groups of sol–gel-derived silica–titania fibrous meshes with precursor ratios of Ti:Si = 7:3, 1:1, 3:7 were fabricated by electrospinning. The effects of silica content on the crystal phase and morphology of silica–titania hybrid nanofiber meshes were also analyzed by scanning electron microscopy, X-ray diffraction, and laser confocal microscopy. The osteogenic potential of the silica–titania meshes was evaluated by seeding mesenchymal stem cells (MSCs) on each mesh and determining cell number, osteodifferentiation markers, and osteopontin production over time. Our results show that cells proliferated throughout the mesh surfaces with similar morphology in all groups. Decreased cell proliferation was observed with the fiber meshes compared with glass controls, whereas cell differentiation toward osteoblast was enhanced on the mesh groups, especially on the Ti:Si = 7:3 group. These findings suggest that higher fiber diameter, degree of crystallization, and titania content of nanofibers can enhance osteodifferentiation of MSCs. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A:3511–3517, 2012.