Integrins as linker proteins between osteoblasts and bone replacing materials. A critical review

Siebers, Marijke C.; Brugge, P.J. ter; Walboomers, X. Frank; Jansen, John A.

doi:10.1016/j.biomaterials.2004.02.021

Cited by 310 publications

(255 citation statements)

References 93 publications

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“…A successful cellular replacement for periosteum should be designed to offer the directional bone growth, eg, to inhibit fibrotic tissue formation while promoting differentiation, proliferation, and directional migration of osteoblastic cells along bone allograft surface. Several innovative approaches have been used to add appropriate surface topographies to membranes in guided tissue regeneration for periodontal tissue regeneration [70,81]. Conceivably, these techniques could also be used in our current design for regeneration of periosteal bone formation.…”

Section: Design Rationale and Outcome Evaluations For Tissue-engineermentioning

confidence: 99%

A Perspective: Engineering Periosteum for Structural Bone Graft Healing

Zhang

Awad

O’Keefe

et al. 2008

Clin Orthop Relat Res

206

169

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Autograft is superior to both allograft and synthetic bone graft in repair of large structural bone defect largely due to the presence of multipotent mesenchymal stem cells in periosteum. Recent studies have provided further evidence that activation, expansion and differentiation of the donor periosteal progenitor cells are essential for the initiation of osteogenesis and angiogenesis of donor bone graft healing. The formation of donor cell-derived periosteal callus enables efficient host-dependent graft repair and remodeling at the later stage of healing. Removal of periosteum from bone autograft markedly impairs healing whereas engraftment of multipotent mesenchymal stem cells on bone allograft improves healing and graft incorporation. These studies provide rationale for fabrication of a biomimetic periosteum substitute that could fit bone of any size and shape for enhanced allograft healing and repair. The success of such an approach will depend on further understanding of the molecular signals that control inflammation, cellular recruitment as well as mesenchymal stem cell differentiation and expansion during the early phase of the repair process. It will also depend on multidisciplinary collaborations between biologists, material scientists and bioengineers to address issues of material selection and modification, biological and biomechanical parameters for functional evaluation of bone allograft healing.

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Section: Design Rationale and Outcome Evaluations For Tissue-engineermentioning

confidence: 99%

A Perspective: Engineering Periosteum for Structural Bone Graft Healing

Zhang

Awad

O’Keefe

et al. 2008

Clin Orthop Relat Res

206

169

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“…However, integrin expression is substratesensitive (40,41); thus assumptions about cell behavior based on TCPS may not be relevant for cells on implant materials (37,42). Osteoblasts express primarily ␣5␤1 when grown on TCPS, but they shift to expression of ␣2␤1 when grown on Ti and Ti-6Al-4V (43,44). The consequences of this shift to the cell are not well understood, nor is it known whether integrin expression is sensitive to surface morphology or surface energy.…”

mentioning

confidence: 99%

Integrin α2β1 plays a critical role in osteoblast response to micron-scale surface structure and surface energy of titanium substrates

Olivares-Navarrete

Raz

Zhao

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

215

182

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Efforts to improve bone response to biomaterials have focused on ligands that bind ␣5␤1 integrins. However, antibodies to ␣5␤1 reduce osteoblast proliferation but do not affect differentiation when cells are grown on titanium (Ti). ␤1-silencing blocks the differentiation stimulus of Ti microtopography, suggesting that other ␤1 partners are important. Stably ␣2-silenced MG63 human osteoblast-like cells were used to test whether ␣2␤1 specifically mediates osteoblast response to Ti surface micron-scale structure and energy. WT and ␣2-silenced MG63 cells were cultured on tissue culture polystyrene (TCPS) and Ti disks with different surface microtopographies: machined pretreatment (PT) surfaces [mean peak to valley roughness (R a) < 0.02 m], PT surfaces that were grit-blasted and acid-etched (SLA; R a ‫؍‬ 4 m), and SLA with high surface energy (modSLA). Alkaline phosphatase (ALP), ␣2 and ␤1 mRNA, but not ␣5, ␣v, ␤3, type-I collagen, or osteocalcin, increased on SLA and modSLA at 6 days. ␣2 increased at 8 days on TCPS and PT, but remained unchanged on SLA and modSLA. ␣2-protein was reduced 70% in ␣2-siRNA cells, whereas ␣5-mRNA and protein were unaffected. ␣2-knockdown blocked surface-dependent increases in ␤1 and osteocalcin and decreases in cell number and increases in ALP and local factors typical of MG63 cells grown on SLA and modSLA [e.g., prostaglandin E 2, osteoprotegerin, latent and active TGF-␤1, and stimulatory effects of 1␣,25(OH)2D3 on these parameters]. This finding indicates that ␣2␤1 signaling is required for osteoblastic differentiation caused by Ti microstructure and surface energy, suggesting that conclusions based on cell behavior on TCPS are not predictive of behavior on other substrates or the mechanisms involved.␣-2 integrin siRNA ͉ MG63 human osteoblasts ͉ titanium surface roughness T itanium (Ti) and Ti alloys are commonly used as biomaterials because their surface properties provide a biocompatible interface with peri-implant tissues. Strategies for modifying the nature of this interface frequently involve changes to the surface, thereby affecting protein adsorption, cell-substrate interactions, and tissue development (1). A common modification has been to create micron-scale and submicron scale roughness. Preclinical and clinical studies (2-12) show that these surfaces support greater bone-to-implant contact than smooth surfaces.How surface microstructure promotes an osteogenic response is an important question, because bone-forming osteoblasts preferentially colonize bone surfaces that have been preconditioned by bone-resorbing osteoclasts (13), resulting in complex micron-scale and submicron-scale morphologies (14). In vitro experiments using model surfaces indicate that migration, growth, and colony morphology of rat bone marrow cells (15) and osteoblasts (16-18) are sensitive to microstructure. These observations suggest that structural elements can modulate the spatial organization of cells and their ECM.The topography of osteoclast resorption pits in bone can be modeled by using Ti subs...

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“…The influence of substrate on morphogenesis depends on cell type as well as cellular properties such as cytoskeletal organization, cell adhesion, and cell-cell interactions (36). To further our understanding of the regulatory mechanisms of aggrecan, chondrocytes, DIAS cells, and fibroblasts were cultured on ACS for 36 hours.…”

Section: Discussionmentioning

confidence: 99%

Isolation and chondroinduction of a dermis‐isolated, aggrecan‐sensitive subpopulation with high chondrogenic potential

Deng

Athanasiou

2007

Arthritis & Rheumatism

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Objective. To develop a process that yields tissueengineered articular cartilage constructs from skinderived cells.Methods. Dermis-isolated, aggrecan-sensitive (DIAS) cells were isolated using a modified rapid adherence process. The chondrogenic potential was measured by quantitative reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemistry. Filamentous actin (Factin) and vinculin organization was detected using fluorescence microscopy.Results. The rapid adherence process led to a selection of DIAS cells, <10% of the entire population. DIAS cells displayed greater chondroinduction potential, as evidenced by the formation of large numbers of chondrocytic nodules on aggrecan-coated surfaces. In addition, these cells showed higher gene expression and protein production in terms of chondrocytic markers when compared with unpurified dermis cells. Similar patterns of F-actin and vinculin organization were observed between DIAS cells and chondrocytes. Threedimensional constructs from chondroinduced DIAS cells produced greater amounts of cartilage matrix than constructs from the rest of the dermis populations.Conclusion. These findings show a series of steps that work together to form tissue-engineered articular cartilage constructs using DIAS cells. Since skin presents a minimally invasive, relatively abundant cell source for tissue engineering, this study offers evidence of an efficient and stable technique to form cartilage constructs for future cartilage regeneration with autologous cells from skin.

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Integrins as linker proteins between osteoblasts and bone replacing materials. A critical review

Cited by 310 publications

References 93 publications

A Perspective: Engineering Periosteum for Structural Bone Graft Healing

A Perspective: Engineering Periosteum for Structural Bone Graft Healing

Integrin α2β1 plays a critical role in osteoblast response to micron-scale surface structure and surface energy of titanium substrates

Isolation and chondroinduction of a dermis‐isolated, aggrecan‐sensitive subpopulation with high chondrogenic potential

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