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Cited by 398Cellular Mechanics and InteractionsBone Tissue Engineering MaterialsTissue Engineering and Regenerative Medicine

Characterization of topographical effects on macrophage behavior in a foreign body response model

Open access
Chen, Sulin, Jones, Jacqueline A., Xu, Yongan, Low, Hong-Yee, Anderson, James M., Leong, Kam W.·2010·Biomaterials
DOI 10.1016/j.biomaterials.2010.01.074PMC PMC2837101
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Abstract

Current strategies to limit macrophage adhesion, fusion and fibrous capsule formation in the foreign body response have focused on modulating material surface properties. We hypothesize that topography close to biological scale, in the micron and nanometric range, provides a passive approach without bioactive agents to modulate macrophage behavior. In our study, topography-induced changes in macrophage behavior was examined using parallel gratings (250 nm-2 mum line width) imprinted on poly(epsilon-caprolactone) (PCL), poly(lactic acid) (PLA) and poly(dimethyl siloxane) (PDMS). RAW 264.7 cell adhesion and elongation occurred maximally on 500 nm gratings compared to planar controls over 48 h. TNF-alpha and VEGF secretion levels by RAW 264.7 cells showed greatest sensitivity to topographical effects, with reduced levels observed on larger grating sizes at 48 h. In vivo studies at 21 days showed reduced macrophage adhesion density and degree of high cell fusion on 2 mum gratings compared to planar controls. It was concluded that topography affects macrophage behavior in the foreign body response on all polymer surfaces examined. Topography-induced changes, independent of surface chemistry, did not reveal distinctive patterns but do affect cell morphology and cytokine secretion in vitro, and cell adhesion in vivo particularly on larger size topography compared to planar controls.

Verified 2026-10-05 · 1 reference not checked yet

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Crossref · 10.1016/j.biomaterials.2010.01.074

Cites

71 of 72 references verified0 citation errors · 0 not checkable

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Nothing to recompute.

Claims the paper makes

0 of 30 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    The rise in R-ratio was correlated with a larger sub-population of cells that became elongated, defined as R ≥ 2.5 and aligned within 30° of the gratings.

    “The observed increase in R-ratio correlated with an increase in sub-population of cells attaining the elongated morphology, defined as having R ≥ 2.5 and aligned within 30° of the parallel gratings (Figure 4 B).”
    Quote in the paperSubstantial claim
  • Findingown data

    RAW 264.7 cell adhesion and elongation were maximal on 500 nm gratings compared with planar controls over 48 hours.

    “RAW 264.7 cell adhesion and elongation occurred maximally on 500 nm gratings compared to planar controls over 48 hr.”
    Quote in the paperSubstantial claim
  • Findingown data

    The MCP-1 secretion profile followed the same trend as TNF-α secretion.

    “Similarly, the MCP-1 secretion profile shared the same trend as TNF-α secretion (Figure 6 C).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Elongated cells made up less than 25% of the total cell population on each topography.

    “While the fraction of elongated cells on each topography was small (less than 25% of total cell population), statistical significance was observed on 250 nm and 2 μm PCL gratings compared to planar control (*p<0.05), and on 500 nm gratings (**p<0.01).”
    Quote in the paperNot a substantial claim
  • Findingown data

    The low average R-ratio of all adherent cells, below 2, resulted from round cells predominating in the 1.2 to 1.6 R-ratio sub-population.

    “The low average R-ratio of all adherent cells (R<2, Figure 5 I) was due to the round cells predominating in the sub-population (1.2<R<1.6, Figure 5 I, inset).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 36
  • Classified as probably not a substantial claim. 10

  • May combine two claims.

    Findingown data

    At day 21, 25-55% of fields showed high fusion (>90%), while only 28-37% showed low fusion (<10%).

    “Approximately 25-55% of fields on surfaces registered high levels of fusion (>90%) while only 28-37% of fields supported low fusion (<10%).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Average R-ratios on planar PCL imprinted on glass and on Mylar differed significantly and were marginally higher than on planar TCPS and glass controls.

    “The average R-ratios of cells on planar PCL (0 nm) imprinted on glass and on Mylar were significantly different (#p<0.01), and marginally higher than that on planar TCPS and glass controls.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Across grating samples, adherent nuclei density was similar, except that 2 μm gratings had more cells than the planar control at day 21.

    “with comparable nuclei density observed on all grating samples, except for increased cell density on 2 μm gratings compared to planar control at Day 21 (*p<0.05).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Low fusion fell as grating size increased at day 7, but this pattern reversed at day 21.

    “Topography-induced cellular fusion showed that low fusion decreased with increasing grating sizes at Day 7, but the trend reversed at Day 21 (Figure 7 H).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The topographical effect on MIP-1α was hard to discern, but significance occurred at 6 hours for 300 nm versus planar, at 24 hours for 1 μm versus 300 nm and 500 nm, and at 48 hours for 300 nm, 500 nm, and 1 μm versus planar.

    “The topographical effect on MIP-1α secretion was difficult to discern (Figure 6 B) but significance was observed at 6 hr for 300 nm samples compared to planar control (*p<0.05), at 24 hr for 1 μm gratings compared to 300 nm and 500 nm samples (*p<0.01), and at 48 hr for 300 nm, 500 nm and 1 μm gratings compared to planar samples (*p<0.05).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Patterns in topography-induced cytokine secretion were difficult to discern, but greater statistical significance appeared at 24 and 48 hours.

    “Patterns in topography-induced cytokine secretion were difficult to discern but greater statistical significance was observed for 24 hr and 48 hr readings.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Most adherent cells and FBGCs on PCL/Mylar were thinly spread, but some were elongated and extended pseudopodia along the gratings.

    “While most adherent cells and FBGCs displayed a thinly spread morphology on the PCL/Mylar surfaces, some cells displayed elongated morphologies and the extension of pseudopodia in the direction of gratings, confirmed by SEM imaging (Supplementary Figure 4).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    IL-1β, IL-6, IL-10, and IL-12 were not detected in the supernatant, with a detection limit of 3.2 pg/mL.

    “The pro-inflammatory and pro-wound healing cytokine IL-1β, and the anti-inflammatory and pro-wound healing cytokines IL-6, IL-10, and IL-12 were not detected in the supernatant (detection limit: 3.2 pg/mL).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    At day 7, fusion was low on all surfaces: 58-74% of fields had low or no fusion, and 0-5% had high fusion.

    “At Day 7, fusion was minimal on all surfaces with 58-74% of fields having low (<10%) or no fusion (0%), and only 0-5% of fields with high fusion (>90%).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    VEGF was low from 6 to 24 hours, below 0.5 pg/mL per 1000 cells, but increased at 48 hours.

    “In contrast, VEGF was low at 6 hr to 24 hr (<0.5 pg/mL per 1000 cells, Figure 6 D), but increased at 48 hr.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Pattern transfer fidelity was within 8% of the intended feature size, with an observed-to-expected ratio of 1.08.

    “A comparison of the observed values (O) to the expected value (E) of the topographical gratings showed fidelity to be within 8% of expected feature size (O/E value of 1.08).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Topography had no statistically significant effect on the fractional distribution of elongated cells or the average R-ratio.

    “The effect of topography on fractional distribution of elongated cells and average R-ratio was not statistically significant.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Most adherent cells remained round, while elongated cells were less than 15% of total cells.

    “Similar to macrophage adhesion and elongation on PCL gratings, the majority of adherent cells retained their native round shape (Figure 5 G) while elongated cells formed a small fraction, less than 15%, of total cells (Figure 5 F).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    At 24 hours, increasing grating width increased TNF-α secretion, but the trend reversed at 48 hours, with significance for 1 μm versus 300 nm gratings.

    “At 24 hr, increasing grating width increased TNF-α secretion (*p<0.001), but the trend was reversed at 48 hr (*p<0.05), with statistical significance noted for 1 μm gratings compared to 300 nm gratings.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    High fusion was rare at day 7 and tended to decrease with larger grating sizes.

    “In contrast, high fusion was not prevalent at Day 7 but showed a decreasing trend with larger grating sizes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Cell spreading was comparable across grating sizes at 6 and 24 hours but increased significantly on 500 nm and 1 μm gratings compared with planar PDMS controls.

    “Cell spreading of adherent macrophage was comparable across all grating sizes at 6 hr and 24 hr, but increased significantly on 500 nm and 1 μm gratings compared to planar PDMS control (Figure 5 F).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    TNF-α, MIP-1α, MCP-1, and VEGF were detected in the supernatant.

    “TNF-α (tumor necrosis factor-α), MIP-1α (macrophage inflammatory protein-1α), MCP-1 (monocyte chemoattractant protein-1) and VEGF (vascular endothelial growth factor) cytokines were detected in the supernatant.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    RAW 264.7 cells clearly adhered, elongated, and aligned to the underlying topography on PCL and PLA gratings and on PDMS substrates of constant height.

    “Adhesion, elongation and alignment of RAW 264.7 to its underlying topography was clearly observed on PCL and PLA gratings (width:height:period = 1:1:2) and on PDMS substrates of constant height (width:period = 1:2, height = 350 nm), independent of surface chemistry.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In vivo studies at 21 days showed lower macrophage adhesion density and less high cell fusion on 2 μm gratings than on planar controls.

    “In vivo studies at 21 days showed reduced macrophage adhesion density and degree of high cell fusion on 2 μm gratings compared to planar controls.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The rat cage implant model reflects the foreign body response relevant to clinical implants.

  • May combine two claims.

    Findingown data

    The fraction of elongated cells rose from 0.10 on planar controls to 0.17 on 250 nm, 0.23 on 500 nm, and 0.20 on 2 μm gratings.

    “The fraction of elongated cells increased from 0.10 on planar controls to 0.17 (66% increase), 0.23 (123% increase) and 0.20 (85% increase) on 250 nm, 500 nm and 2 μm gratings, respectively.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The average R-ratio was 1.78 on planar controls, 2.18 on 250 nm gratings, 2.53 on 500 nm gratings, and 2.24 on 2 μm gratings.

    “The average R-ratio of macrophages on planar control was 1.78, but increased to 2.18 on 250 nm gratings and 2.53 on 500 nm gratings, and then decreased slightly to 2.24 on 2 μm gratings.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Between 24 and 48 hours, TNF-α, MIP-1α, and MCP-1 levels were maintained or reduced, while VEGF increased.

    “Between 24 hr to 48 hr, the levels of pro-inflammatory cytokines TNF-α, MIP-1α and MCP-1 were maintained or reduced, while VEGF, a pro-inflammation/pro-wound healing cytokine, increased.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The elongated-cell fraction was statistically significant on 250 nm and 2 μm PCL gratings versus planar control and on 500 nm gratings.

    “While the fraction of elongated cells on each topography was small (less than 25% of total cell population), statistical significance was observed on 250 nm and 2 μm PCL gratings compared to planar control (*p<0.05), and on 500 nm gratings (**p<0.01).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Cell adhesion density at 6 hours was low, around 1 × 100 cells/mm2, and did not exceed the seeding density of 2 × 100 cells/mm2 until between 24 and 48 hours, when proliferation occurred.

    “Morphometric analysis of RAW 264.7 response to topography showed that cell adhesion density on 6 hr samples was low (around 1 × 100 cells/mm2) and did not increase above the cell seeding density (at 2 × 100 cells/mm2) until between 24 hr and 48 hr (Figure 5 E), when proliferation occurred.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Topography-induced MCP-1 secretion was most significant at 24 hours, with increasing MCP-1 levels on increasing grating sizes from planar and 300 nm and 500 nm compared with 1 μm, but was hard to discern at 48 hours.

    “Topography-induced MCP-1 secretion was most significant at 24 hr (*p<0.001) with increasing MCP-1 levels on increasing grating sizes: planar (*p<0.01), 300 nm (*p<0.05) and 500 nm (*p<0.05) compared to 1 μm gratings, but was difficult to discern at 48 hr.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In this system, macrophage elongation increased as topography size decreased, but only down to 500 nm, after which the trend diverged.

    “Macrophage cells studies in our system showed that elongation increased with decreasing topography, but only to a limit of 500 nm before the trend diverged.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    At 21 days, high cellular fusion (>90%) decreased as grating size increased, with high fusion on planar > 500 nm > 2 μm.

    “In the long term response (21 days), high cellular fusion (>90%) was reduced as grating sizes increased: represented as high fusion on planar > 500 nm > 2 μm (Figure 7 G).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Each grating size was tested in triplicate at each time point.

    “Triplicates (n=3) of each grating size were used for each time point.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Topography affects cell morphology and cytokine secretion in vitro.

    “but do affect cell morphology and cytokine secretion in vitro”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The RAW 264.7 murine macrophage cell line is a valid model for macrophage behavior in the foreign body response.
    • Rests on an assumption: Differences in surface chemistry among PCL, PLA, and PDMS do not confound the observed effects of topography.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The Bio-Plex reader was calibrated and validated before every reading according to the manufacturer's instructions.

    “The Bio-Plex reader was calibrated and validated prior to every reading, strictly following the manufacturer's instructions.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All animal protocols were approved by the Institutional Animal Care and Use Committee of Case Western Reserve University.

    “All protocols were approved by the Institutional Animal Care and Use Committee of Case Western Reserve University.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Macrophages in this system showed no distinctive morphology or orientation trends with topography, unlike mesenchymal stem cells and smooth muscle cells, which had over 80% elongation and alignment.

    “The lack of distinctive trends in cell morphology and orientation changes of both RAW 264.7 and in vivo macrophage cells to the topography differed from our previous studies involving other cell types, such as mesenchymal stem cells [26] and smooth muscle cells [45], that showed over 80% cell elongation and alignment.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [26] Yim, 2007, Synthetic nanostructures inducing differentiation of human mesenchymal stem cells into neuronal lineage, Exp Cell Res source

      Not checked in the free run.

    • cites [45] Yim, 2005, Nanopattern-induced changes in morphology and motility of smooth muscle cells, Biomaterials source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Morphology measurements used at least 150 cells in each triplicate sample per grating size.

    “Morphology measurements were made from at least 150 cells in each triplicate sample (n=3) per grating size.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    The cage implant model is an established system for studying host tissue-implant responses.

    “using the cage implant model, an established system for studying host tissue-implant response [44].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [44] Miller, 1989, Generation of IL-1-like activity in response to biomedical polymer implants: a comparison of in vitro and in vivo models, J Biomed Mater Res source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    SEM imaging confirmed the elongated morphologies and pseudopodia.

    “confirmed by SEM imaging (Supplementary Figure 4)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Larger topography (500 nm-2 μm) limits macrophage activation and inflammation-related processes, but topography-induced sensitivity reaches a limit around 500 nm.

    “Our results suggest that larger size topography (500 nm-2 μm) limits macrophage activation and inflammation-related processes but topography-induced sensitivity reaches a limit around 500 nm.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    MCP-1 stimulates murine FBGC fusion in vivo.

    “MCP-1 (macrophage chemoattractant protein-1), a chemokine that recruits macrophage and promotes migration, also stimulates murine FBGC fusion in vivo [54].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [54] Kyriakides, 2004, The CC chemokine ligand, CCL2/MCP1, participates in macrophage fusion and foreign body giant cell formation, Am J Pathol source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Although micro- to submicron gratings did not produce a distinctive pattern, topography affects cell morphology, in vitro cytokine secretion, and in vivo cell adhesion, especially for larger patterns compared with planar controls.

    “Although the response to topography in the form of gratings from micro- to submicron scale has not revealed a distinctive pattern, topography indeed affects cell morphology, cytokine secretion in vitro, and cell adhesion in vivo particularly for larger size patterns compared to planar controls.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    MIP-1α participates in chemotaxis and recruitment of monocytes and leukocytes during inflammation.

    “while MIP-1α is involved in chemotaxis and recruitment of monocytes and leukocytes during the inflammatory response.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    The macrophage size sensitivity resembles phagocytosis, in which micron-scale particles are internalized more than nanoscale particles, with peak phagocytosis near 2 μm diameter.

    “The phenomenon appears to mirror that of phagocytosis, where macrophages preferentially internalize particulates in the micron range over the nanometric range, with peak phagocytosis observed with particles of approximately 2 μm in diameter [46-48].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [46] Ahsan, 2002, Targeting to macrophages: role of physicochemical properties of particulate carriers–liposomes and microspheres – on the phagocytosis by macrophages, J Control Release source

      Not checked in the free run.

    • cites [47] Schafer, 1992, Phagocytosis of nanoparticles by human immunodeficiency virus (HIV)-infected macrophages: a possibility for antiviral drug targeting, Pharm Res source

      Not checked in the free run.

    • cites [48] Tabata, 1988, Effect of the size and surface charge of polymer microspheres on their phagocytosis by macrophage, Biomaterials source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Larger topographical cues (2 μm gratings) may physically interrupt or constrain fibrous scar tissue formation, reducing cell adhesion density and limiting FBGC fusion compared with planar controls.

    “The larger topographical cues (2 μm gratings) could be presenting a physical interruption or constraint to the fibrous scar tissue formation process, reducing cell adhesion density and limiting FBGC fusion on larger gratings compared to planar controls.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationcitation

    The limit of macrophage sensitivity to nanotopographical cues could be compared to surface-area dependence of nanoparticle pro-inflammatory responses and to particle shape and size effects on internalization kinetics.

    “While the infinitely long parallel gratings, compared to a cell dimension, provide a non-phagocytosable surface, the limit of macrophage sensitivity to nanotopographical cues could be compared to a surface area dependence on pro-inflammation response, analogous to surface area dependence of nanoparticles in determining inflammatory response [50, 51], and the influence of particle shape and size on”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [50] Limbach, 2005, Oxide nanoparticle uptake in human lung fibroblasts: effects of particle size, agglomeration, and diffusion at low concentrations, Environ Sci Technol source

      Not checked in the free run.

    • cites [51] Hussain, 2009, Oxidative stress and proinflammatory effects of carbon black and titanium dioxide nanoparticles: role of particle surface area and internalized amount, Toxicology source

      Not checked in the free run.

    • cites [52] Gratton, 2008, The effect of particle design on cellular internalization pathways, Proc Natl Acad Sci U S A source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Macrophages seemed relatively insensitive to nanotopography below 500 nm and preferred to respond to 500 nm, 1 μm, and 2 μm gratings.

    “Macrophage cells appeared to be relatively insensitive to nanotopography (less than 500 nm), preferring to respond to 500 nm, 1 μm and 2 μm gratings.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    VEGF promotes blood vessel dilation and angiogenesis during inflammation to aid wound healing in damaged tissue.

    “VEGF promotes blood vessel dilation and angiogenesis in the event of inflammation to promote wound healing in damaged tissue.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Cellular responses to topography affect cell function, including adhesion strength, spreading, intracellular signaling, and differentiation potential.

    “Cellular responses to topography are known to affect cell function in terms of adhesion strength, spreading, intracellular signaling and differentiation potential [59-61].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [59] Kulangara, 2009, Substrate topography shapes cell function, Soft Matter source

      Not checked in the free run.

    • cites [60] Vogel, 2006, Local force and geometry sensing regulate cell functions, Nat Rev Mol Cell Biol source

      Not checked in the free run.

    • cites [61] Yim, 2005, Significance of synthetic nanostructures in dictating cellular response, Nanomedicine source

      Not checked in the free run.

45 of 45

  • The paper relies on this without support.

    The RAW 264.7 murine macrophage cell line is a valid model for macrophage behavior in the foreign body response.

    “Adherent murine macrophage cell line, RAW 264.7 (ATCC, Manassas, VA), was grown in Dulbecco's Modified Eagle's Medium (DMEM) cell culture media supplemented with 10% fetal bovine serum, penicillin (100 μg/mL) and streptomycin (100 μg/mL).”

  • The paper relies on this without support.

    The rat cage implant model reflects the foreign body response relevant to clinical implants.

    “Samples of PCL gratings nanoimprinted on Mylar were evaluated in rats using the cage implant model to determine the effect of topography on foreign body reaction.”

  • The paper relies on this without support.

    Differences in surface chemistry among PCL, PLA, and PDMS do not confound the observed effects of topography.

    “RAW 264.7 was cultured on 3 different types of polymers, PCL, PLA and PDMS gratings, to examine macrophage response to topography independent of surface chemistry.”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Upregulation of TNF-α and VEGF provided a mixture of M1 and M2 phenotype in smaller gratings (higher surface roughness).

    “Upregulation of TNF‐α and VEGF provided a mixture of M1 and M2 phenotype in smaller gratings (higher surface roughness).”

    From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [147]

    The Results (§3.4; page unavailable) report higher TNF-α and VEGF secretion on smaller gratings than on 1 μm gratings at 48 hours, and the Discussion (§4; page unavailable) identifies them as pro-inflammatory and pro-wound-healing cytokines, respectively. The paper does not establish a mixed M1/M2 phenotype or identify smaller gratings as having higher surface roughness; its cytokine findings also vary by time point. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Chen et al. confirmed topography-induced polarization on PCL, PLA, and poly(dimethyl siloxane) imprinted with 250-2000 nm grooves.

    “Chen et al. confirmed this topography‐induced polarization on PCL, poly(lactic acid) (PLA), and poly(dimethyl siloxane) imprinted with 250–2000 nm grooves.[ 147 ]”

    From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [147]

    The Introduction and Results §3.2 report PCL, PLA, and PDMS gratings and macrophage elongation in response to their topography. They do not establish macrophage polarization as a functional phenotype: the reported response is primarily morphological. Methods §2.1 also specifies 300–1000 nm widths for PDMS, rather than the full 250–2000 nm range implied for all three materials. Page numbers are unavailable in our copy. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Seeded RAW 264.7 established its longest elongation in 500 nm grooves.

    “Seeded RAW 264.7 established its longest elongation in 500 nm grooves.”

    From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [147]

  • Irregular topographies with dimensions similar to aligned patterns produce circularly spreading macrophages with M1 characteristics.

    “irregular topographies with similar dimensions produce circularly spreading macrophages with M1 characteristics”

    From Modeling mechanical activation of macrophages during pulmonary fibrogenesis for targeted anti-fibrosis therapy (2024) · cites this paper as [39]

  • Aligned patterns with micron-level feature sizes promote M2 macrophage differentiation through forced alignment.

    “Aligned patterns with feature sizes in the micron level were shown to promote M2 macrophage differentiation through forced alignment”

    From Modeling mechanical activation of macrophages during pulmonary fibrogenesis for targeted anti-fibrosis therapy (2024) · cites this paper as [39]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Day-21 adhesion trend is reversed in the abstract

    Major

    The abstract says macrophage adhesion density was lower on 2 μm gratings than on planar controls at 21 days. The results report a statistically significant increase on those gratings at Day 21, reversing the stated conclusion.

1 of 1

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Related

Authors
Chen, S., Jones, J. A., Xu, Y., Low, H.-Y., Anderson, J. M., & Leong, K. W.
Affiliations
  • Johns Hopkins University (US)
  • Case Western Reserve University (US)
  • Institute of Materials Research and Engineering (SG)
  • Duke University (US)
Corresponding author
Leong, Kam W.
ORCID
Venue
Biomaterials
Publisher
Elsevier BV
Published
2010-05
Volume
31
Issue
13
Pages
3479-3491
ISSN
0142-9612 (ISSN-L)
DOI
10.1016/j.biomaterials.2010.01.074
PMC
PMC2837101
OpenAlex
W2038846800
Cited by
389
References
73
Citations by year
2026: 13 · 2025: 21 · 2024: 21 · 2023: 24 · 2022: 30 · 2021: 38 · 2020: 28 · 2019: 31 · 2018: 23 · 2017: 32 · 2016: 24 · 2015: 24 · 2014: 30 · 2013: 16 · 2012: 15
FWCI
7.00
Type
journal article
Language
en
Open access
Licence
Locations
  • Biomaterials (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • DukeSpace (Duke University) (submittedVersion, cc-by-nc-nd)
Funders
National Institutes of Health (EB000282, HL83008)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
topography, foreign body reaction, cell adhesion, cell fusion, fibrous capsule formation, TNF-α, vascular endothelial growth factor, RAW 264.7 macrophages, polycaprolactone, polylactic acid, polydimethylsiloxane
MeSH terms
Animals, Cell Line, Foreign-Body Reaction, Macrophages, Microscopy, Electron, Scanning, Models, Biological, Polymers, Surface Properties, Tumor Necrosis Factor-alpha, Vascular Endothelial Growth Factor A, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-05.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-05.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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