Table 1.

Fibronectin (keyword: fibronectin and osteoblast, 2006–2011 and published in English)

Author	Type	Cell	Objective	Result
Hindé et al. [83]	In vitro	MC3T3-E1 osteoblast-like cells	To study MC3T3-E1 osteoblast-like cell behavior on silicon oxide and PLLA substrates with a focus on the influence of the adhesive protein fibronectin and the non-adhesive protein albumin adsorbed on the substrates	PLLA substrates coated with fibronectin and subsequently exposed to albumin exhibited the highest level of cell differentiation, as assayed via alkaline phosphatase activity
Wang et al. [208]	In vitro	Osteoblasts	To investigate the involvement of cell surface receptors and their intracellular signaling molecules to further explore the pathway mediated by this novel TG-FN heterocomplex	A novel cell adhesion/survival mechanism in human osteoblasts requires association of FN bound TG2 with the cell surface heparan sulphates in a transamidase-independent manner
Bentmann et al. [64]	In vivo; transgenic mice		To identify the receptor involved in fibronectin effects on osteoblasts	Osteoblast fibronectin affects osteoblasts function. This does not seem to be mediated by the RGD motif on fibronectin. In contrast, liver-derived fibronectin affects bone matrix properties without affecting osteoblast or osteoclast function
Cairns et al. [65]	In vitro	MG63 osteoblast-like cells	To investigate the role of surface topography in determining the nature of this cell-protein-surface interaction	The presence of the adsorbed FN layer on the CaP thin films improved MG63 cell adhesion, proliferation, and promoted early onset differentiation
Chen et al. [106]	In vitro		To investigate the details of apatite nucleation and growth on the coating layer in Dulbecco’s phosphate-buffered saline solutions containing calcium chloride (DPBS) or DPBS with fibronectin (DPBSF)	The presence of fibronectin in the DPBS solutions delayed the formation and affected the morphology of the apatite. Fibronectin incorporated into apatite deposited on the surface of titanium did not affect its biological activity in terms of promoting osteoblast adhesion
Gonzalez-Garcia et al. [66]	In vitro	MC3T3 osteoblast-like cells	To investigate the influence of deep pit on biological activity of FN	FN reorganization only takes places on the 29- and 45-nm-deep pit surfaces, where enhanced late matrix production was found
Pegueroles et al. [70]	In vitro	MG63 osteoblast-like cells	To investigate the early events of bone matrix formation, and specifically the role of fibronectin (FN) in the initial osteoblast interaction and the subsequent organization of a provisional FN matrix on different rough titanium (Ti) surfaces	Osteoblasts deposit FN fibrils in a specific facet-like pattern that is organized within the secreted total matrix overlying the top of the samples. The thickness of this FN layer increased when the roughness of the underlying topography was increased, but not by more than half of the total maximum peak-to-valley distance
Ribeiro et al. [55]	In vitro	MC3T3-E1 osteoblast-like cells	To analyze the influence of two distinct nanophased HA ceramics, (HA725 and HA1000) on FN and osteonectin adsorption	FN as an adhesive glycoprotein and osteonectin as a counter-adhesive protein, are known to be involved in the early stages of osteogenesis. However, the osteoblast adhesion and metabolic activity seemed to be more sensitive to surfaces morphology and roughness than to the type of adsorbed proteins
Zhang et al. [83]	In vitro	hMSC	To investigate the effects of a bio-inspired ceramic surface modified with a novel recombinant protein on surface parameters and cell behavior	The fibronectin module III7-10 and extracellular domains 1 and 2 of cadherin 11 bio-inspired ceramic surface possesses enhanced functionality in adhesion, proliferation and ossification and may be a promising scaffold for tissue engineering
Ball et al. [60]	In vitro		To explore the possibility of controlling cell interaction with biomaterials, tricalcium phosphate scaffolds were modified using the enzyme tissue transglutaminase (tTgase) in conjunction with fibronectin	The mixture of fibronectin and transglutaminase may prove to be a useful treatment for producing increased osteoblast differentiation on scaffolds
Forsprecher et al. [61]	In vitro	MC3T3-E1 osteoblast	To test the effects of extracellular FN, before and after in vitro crosslinking and polymerization by TG2	TG2-mediated crosslinking enhances the cell-adhesive properties of FN by increasing the molecular rigidity of FN in the extracellular matrix
Muhonen et al. [84]	In vitro	MC3T3-E1 osteoblast	To investigate the effect of two phases of Nitinol with plasma fibronectin and studied if this modifies the proliferation and cell cycle of MC3T3-E1 osteoblasts	Fibronectin improved cell proliferation in both phases, but the effect of fibronectin coating was stronger on the austenite surface. In both Nitinol phases, the proportion of cells in the G(1) phase was observed to grow in the presence of fibronectin. This could indicate cell differentiation on Nitinol
Rico et al. [56]	In vitro		To investigate the influence of surface chemistry and effect on osteoblast adhesion	FN adsorption is correlated with human osteoblast adhesion through morphology and actin cytoskeleton formation. Actin polymerization is in need of the formation of the protein network on the substrate’s surface. Cell morphology is more rounded when the degree of FN fibrillogenesis on the substrate is lower
Shahryari et al. [57]	In vitro		To investigate the influence of an electrochemical surface passivation technique (cyclic potentiodynamic polarization, CPP) on the physico-chemical surface properties of SS316LS and its subsequent response to FN and pre-osteoblasts	The attachment, proliferation, and morphology of pre-osteoblasts were significantly improved on the CPP-modified surface, which was attributed to the more open conformation of Fn on the CPP-modified surface. Thus, the CPP surface passivation method was demonstrated to yield a SS316LS surface of enhanced biocompatibility
Toworfe et al. [67]	In vitro	MC3T3-E1	To investigate the effect of silane self-assembled monolayer surfaces on apatite formation, fibronectin adsorption, and osteoblast cell function	FN monolayer coverage and the root mean square (rms) roughness are similar on –OH and –COOH terminated self-assembles monolayers with or without CaP coating, higher levels of ALP activity, more actin cytoskeleton formation, and more cell growth are obtained on –OH– and –COOH–terminated SAMs with CaP coating
Tsai et al. [68]	In vitro	MG-63 osteoblast-like cells	To investigate the morphology of osteoblast on nano-grooved substrates	FN coating initially modulated cellular spreading, length, and orientation on all types of grooved surfaces. After 24 h of culture, the cell morphology was not affected by FN coating on the 250- and 500-nm surfaces, while FN decreased cell alignment on the 90-nm surfaces
Woo et al. [62]	In vitro	hESCs	To investigate the effect of electronical stimulation on the differentiation of hESCs adhered onto fibronectin-coated gold nanoparticles	Evaluation of gene-modified hESCs that were subsequently attached onto fibronectin-coated gold nanoparticles revealed that the un-differentiation marker, Oct-4, was no longer present following electrical stimulation
Schonmeyr et al. [73]	In vitro, in vivo; mice	Bone-firming cells	To study the result of the treatment of HA scaffolds with FN and fetal calf serum	In vitro attachment and proliferation of bone-forming cells on hydroxyapatite is significantly increased by pretreatment with fibronectin/fetal calf serum, but this difference is less profound and not significant in vivo
Sousa et al. [76]	In vitro	MC3T3-E2 osteoblast	To assess the influence of the competitive preadsorption of human serum albumin (HSA) and human plasma FN from binary solutions and 10 % plasma on MC3T3-E1 osteoblast adhesion and morphology on two types of TiO2 substrates	FN reversibility does not seem to be dependent on the HSA/FN adsorption mass ratio in solution, suggesting that FN competitively adsorbs to TiO2 in a favorable conformation and does not suffer subsequent conformational changes allowing exchange with other FN molecules in solution
Jimbo et al. [79]	In vitro, in vivo; mouse femur	BMSCs	To clarify the role of pFN during osseointegration	The in vivo results showed that faster direct bone formation was seen for the FN-Ti-acryl group compared to the Ti-acryl group. The in vitro results showed that pFN significantly promoted BMSCs chemotaxis, however, had no effect on proliferation or differentiation. The results indicate that pFN regulated chemotaxis of osteogenic cells and coating the implant with pFN enhanced earlier osseointegration
Pugdee et al. [78]	In vitro	MC3T3-E2 osteoblast	To examine the cell attachment and gene expression of MC3T3-E1 cells on FN-immobilized titanium using GeneChip	Cells attached on FN-immobilized titanium at a higher rate than untreated titanium. The immobilization of FN on tresylated titanium promoted early matrix mineralization and bone formation
Sogo et al. [75]	In vitro	hMSCs	To investigate FN-calcium phosphate composite layer on HA	The FN-calcium phosphate composite layer formed on the HA is useful for the enhancement of the spreading and osteogenic differentiation of hMSCs in vitro
Tang et al. [59]	In vitro	Osteoblast	To show basic fibroblast growth factor stimulates fibronectin expression through phospholipase C gamma, protein kinase C alpha, c-Src, NF-kappaB, and p300 pathway in osteoblasts	bFGF increased Fn expression in rat osteoblasts via the FGFR2/PLCgamma2/PKCalpha/c-Src/NF-kappaB signaling pathway
Deligianni et al. [69]	In vitro	Human osteoblasts	To investigate the contribution of fibronectin preadsorption to enhance the osteoblasts’ adhesion and strength on hydroxyapatite	Fibronectin preadsorption increased the number of attached osteoblasts on smooth and rough hydroxyapatite substratum at 40 and 62 %, respectively, while it increased osteoblast attachment strength on the smooth and rough substratum at 165 and 73 %, respectively
Ding et al. [53]	In vitro	Vascular smooth muscle cells	To investigated the effect of FN on the calcification of vascular smooth muscle cells	FN enhanced vascular calcification by promoting the osteoblastic differentiation of vascular smooth muscle cells via ERK signal pathway
Kennedy et al. [54]	In vitro	Osteoblast	To study the effect of surface energy on fibronectin-mediated cell response	FN-mediated cell spreading and proliferation are dependent on surface energy and establish a new combinatorial approach for screening cell response to changes in surface energy
Osathanon et al. [80]	In vitro	SaOS-2 human osteoblast-like cells	To compare the early response of human osteoblast-like cells (SaOS-2) on commercially pure titanium (cpTi) and titanium-6-aluminium-7-niobium (Ti-6Al-7Nb)	Ti-6Al-7Nb possess a good potential to support SaOS-2 cells on spreading and fibronectin and osteopontin synthesis, therefore, this material may be one of a candidate material used in implant dentistry
Park et al. [81]	In vivo; rabbit tibiae		To evaluate the bone response around anodized titanium implants treated with FGF-FN fusion protein using the histomorphometric analysis and the removal torque test	FGF-FN fusion protein coating on anodized implants may enhance osseointegration