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Cited by 457Electrospun Nanofibers in Biomedical ApplicationsBone Tissue Engineering MaterialsTissue Engineering and Regenerative Medicine

Macrophage functional polarization (M1/M2) in response to varying fiber and pore dimensions of electrospun scaffolds

Open access
Garg, Koyal, Pullen, Nicholas A., Oskeritzian, Carole A., Ryan, John J., Bowlin, Gary L.·2013·Biomaterials
DOI 10.1016/j.biomaterials.2013.02.065PMC PMC3623371
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Abstract

In this study, we investigated the effect of fiber and pore size of an electrospun scaffold on the polarization of mouse bone marrow-derived macrophages (BMMΦs) towards regenerative (M2) or inflammatory (M1) phenotypes. BMMΦs were seeded on Polydioxanone (PDO) scaffolds electrospun from varying polymer concentrations (60, 100, and 140 mg/ml). Higher polymer concentrations yielded larger diameter fibers with larger pore sizes and porosity. BMMΦ cultured on these scaffolds showed a correlation between increasing fiber/pore size and increased expression of the M2 marker Arginase 1 (Arg1), along with decreased expression of the M1 marker inducible nitric oxide synthase (iNOS). Secretion of the angiogenic cytokines VEGF, TGF-β1 and bFGF was higher among cultures employing larger fiber/pore size scaffolds (140 mg/ml). Using a 3D in vitro angiogenesis bead assay, we have demonstrated that the M2-like profile of BMMΦ induced by the 140 mg/ml is functional. Furthermore, our results show that the pore size of a scaffold is a more critical regulator of the BMMΦ polarization compared to the fiber diameter. The study also shows a potential role for MyD88 in regulating M1 BMMΦ signaling on the large vs. small fiber/pore size PDO scaffold. These data are instructive for the rationale design of implantable prosthetics designed to promote in situ regeneration.

Integrity signals

Registry

Crossref · 10.1016/j.biomaterials.2013.02.065

Cites

43 of 43 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 23 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    BMMΦ (M0s and M2s) infiltration into the fibrous structures was greater in larger fiber/pore size scaffolds.

    “The histological evaluation (H&E staining) of PDO scaffolds showed greater BMMΦ (M0s and M2s) infiltration into the fibrous structures of larger fiber/pore size scaffold (Figure 4A).”
    Quote in the paperSubstantial claim
  • Findingown data

    Larger fiber/pore sizes induce statistically higher Arg1 expression.

    “The larger fiber/pore sizes are able to induce statistically higher Arg1 expression.”
    Quote in the paperSubstantial claim
  • Findingown data

    BMMΦ infiltration was statistically higher in the large fiber/pore size scaffold (140 mg/ml) than in the 60 mg/ml scaffold for M0s and M2s.

    “The BMMΦ infiltration was statistically higher in the large fiber/pore size scaffold (140 mg/ml) when compared to the 60 mg/ml scaffold.”
    Quote in the paperSubstantial claim
  • Findingown data

    Secretion of VEGF, TGF-β1, and bFGF was higher in cultures with larger fiber/pore size scaffolds (140 mg/ml).

    “Secretion of the angiogenic cytokines VEGF, TGF-β1 and bFGF was higher among cultures employing larger fiber/pore size scaffolds (140 mg/ml).”
    Quote in the paperSubstantial claim
  • Findingown data

    M0s and M2s on the small fiber/pore size PDO (60 mg/ml) scaffold were concentrated at the surface.

    “The M0s and M2s in the case of small fiber/pore size PDO (60 mg/ml) scaffold were found concentrated at the surface.”
    Quote in the paperNot a substantial claim
  • May combine two claims. 22
  • Classified as probably not a substantial claim. 12

  • May combine two claims.

    Findingown data

    Compressing 140 mg/ml PDO scaffolds reduced pore size from 14 μm to 9 μm without impacting fiber size.

    “This led to a decrease in the pore size of the scaffold from 14 µm to 9 µm without impacting the fiber size.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Statistical differences in scaffold properties were observed only between 60 mg/ml and 140 mg/ml scaffolds; 100 mg/ml and 140 mg/ml scaffolds were not statistically different.

    “The statistical differences were only observed in the case of 60 mg/ml and 140 mg/ml scaffolds. The properties of 100 mg/ml and 140 mg/ml scaffolds were not statistically different from one another.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In M1 pre-polarized BMMΦ, iNOS expression is downregulated by increasing fiber/pore size, with statistical difference only between 100 mg/ml and 140 mg/ml PDO scaffolds.

    “The expression of iNOS in M1 pre-polarized BMMΦ is downregulated by increasing fiber/pore size (Figures 5A and C). However, it should be noted that the statistical difference was only found between 100 mg/ml and 140 mg/ml PDO scaffold.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    The 60 mg/ml PDO scaffold was made more porous using air-flow impedance electrospinning without significantly changing its fiber size.

    “In order to investigate which property of the PDO scaffolds plays an important role in BMMΦ phenotype modulation, the 60 mg/ml PDO scaffolds were made more porous and the 140 mg/ml PDO scaffolds were made less porous without significantly changing their fiber size.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Increasing the PDO polymer concentration during electrospinning linearly increased fiber size, pore size, and porosity, while decreasing the surface area to volume ratio.

    “Higher polymer concentrations yielded larger diameter fibers with larger pore sizes and porosity.”
    • Also stated in: § 3.1 Electrospun PDO Properties · plain
      “Increasing the polymer concentration led to a linear increase in the fiber sizes, pore sizes and porosity but decreased the surface area to volume ratio.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The air-flow impedance method produced a statistically significant increase in scaffold pore size and porosity but did not affect fiber size or the surface area to volume ratio.

    “The air-flow impedance method created a statistically significant increase in the pore size and porosity of the scaffold but did not impact the fiber size and the surface area to volume ratio.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    Macrophage conditioned media, especially from the 140 mg/ml scaffold, produced greater average sprout length and higher percentage sprout density than the 20 ng/ml VEGF positive control.

    “BMMΦ conditioned media (especially in the case of 140 mg/ml scaffold) produced greater average length of sprouts and higher percentage density of sprouts compared to the positive control.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    bFGF production was statistically higher on the 140 mg/ml scaffold than the 60 mg/ml scaffold on Day 1 for M0s and M1s and on Day 3 for M2s.

    “The production of bFGF was statistically higher on the 140 mg/ml scaffold compared to the 60 mg/ml scaffold on Day 1 in the case of M0s and M1s and on Day 3 in the case of M2s.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    TNF-α levels fell by Day 3 and trended lower on the 140 mg/ml scaffold.

    “TNF-α levels decreased on Day 3 and trended lower on the 140 mg/ml scaffold.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    M0 macrophages induced about 200-fold higher and M2 macrophages about 2-fold higher sprout length from the 140 mg/ml compared to the 60 mg/ml PDO scaffolds.

    “Overall it was observed that M0s induced a ~200 fold higher and M2s induced a ~2 fold higher length of sprout from the 140 mg/ml compared to the 60 mg/ml PDO scaffolds.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Compared with the 60 mg/ml scaffolds, the 140 mg/ml scaffolds induced a 94-fold higher sprout density from M0s, 7-fold from M1s and 17-fold from M2s.

    “Compared to the 60 mg/ml scaffolds, the 140 mg/ml scaffolds induced a 94 fold higher density of sprouts from M0s, 7 fold higher density of sprouts from M1s and 17 fold higher density of sprouts from M2s.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    TGF-β1 production was statistically higher on the 140 mg/ml scaffold than the 60 mg/ml scaffold on Day 1 for M0s and on both Day 1 and Day 3 for M1s and M2s.

    “The production of TGF-β1 was statistically higher on the 140 mg/ml scaffold compared to the 60 mg/ml scaffold on Day 1 in the case of M0s and on both Day 1 and 3 in the case of M1s and M2s.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    IL-6 levels were not downregulated by the large fiber/pore size PDO and were unaffected by fiber/pore size on either Day 1 or Day 3.

    “Similar to TNF-α, the levels of IL-6 were not downregulated by the large fiber/pore size PDO.”
    • Also stated in: § 3.5 BMMΦ Mediator Secretion · plain
      “IL-6 levels were unaffected by different fiber/pore sizes on either Day 1 or 3.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    Each experiment was done in triplicates and was reproduced at least twice.

    “Each experiment was done in triplicates and was reproduced at least twice.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationown data

    The data are instructive for rational design of implantable prosthetics to promote in situ regeneration.

    “These data are instructive for the rationale design of implantable prosthetics designed to promote in situ regeneration.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: In vitro BMMΦ responses to PDO scaffolds predict in vivo regeneration.

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

    Premisecitation

    MΦ phenotype is a continuum of functional states between M1 and M2.

    “The actual MΦ phenotype is viewed as a continuum of functional states between these two opposing ends [13].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] Kou, 2011, Macrophage and dendritic cell phenotypic diversity in the context of biomaterials, J Biomed Mater Res A source

      Not checked in the free run.

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

    Premisecitation

    M1s invade tissues by degrading and destroying them to clear pathogens and debris.

    “It is known that M1s invade tissues by degrading and destroying it in an attempt to clear the tissue of pathogens and debris [13].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] Kou, 2011, Macrophage and dendritic cell phenotypic diversity in the context of biomaterials, J Biomed Mater Res A source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    PDO scaffolds used in the study were endotoxin-free, with endotoxin levels 0.03-0.09 EU/ml, at least 12,000 times lower than the LPS concentration used to activate BMMΦs and below the USP standard of <0.25 EU/ml.

    “The values for endotoxin content ranged from 0.03 – 0.09 EU/ml. Therefore, the highest endotoxin level for any scaffold was at least 12,000 times lower than the lowest amount used to activate BMMΦs (100 ng/ml of LPS corresponding to 1100 EU/ml) and well below the acceptable U.S. Pharmacopeia standard for clinical applications (<0.25 EU/ml). This study indicated that the PDO materials used in this”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [31] General chapter <85> bacterial endotoxins test, US pharmacopeia 31-national formulary 26. United States Pharmacopeial Convention, Rockville, MD; 2009.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    PDO exhibits high flexibility, higher strength retention, slower absorption rate, and lower inflammatory response compared to poly(glycolide lactide) and poly(glycolic acid).

    “It exhibits high flexibility, higher strength retention, slower absorption rate, and lower inflammatory response as compared to poly(glycolide lactide) and poly(glycolic acid) [18].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [18] Boland, 2005, Electrospinning polydioxanone for biomedical applications, Acta Biomater source

      Not checked in the free run.

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

    Premisecitation

    The surface area to volume ratio formulas given by Boland et al. were used.

    “The surface area to volume ratio of the scaffolds was calculated using the formulas given by Boland et al. [18]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [18] Boland, 2005, Electrospinning polydioxanone for biomedical applications, Acta Biomater source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Increased fiber/pore size shifts the macrophage phenotype in vitro towards a more M2, tissue regenerative phenotype, as evidenced by increased Arg1, TGF-β1, VEGF and bFGF expression.

    “we have demonstrated that increased fiber/pore size shifts the MΦ phenotype to a more M2, tissue regenerative phenotype in vitro, as evidenced by increased Arg1, TGF-β1, VEGF, bFGF expression.”
    • Also stated in: § 5. Conclusion · boosted
      “BMMΦ acquire a more tissue regenerative M2 phenotype on scaffolds with larger fiber and pore dimensions as evidenced by the increased production of Arg1, VEGF, bFGF and TGF-β1.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: An M2 macrophage phenotype promotes healing and integration of the biomaterial with the host tissue, enhancing tissue regeneration.

  • May combine two claims.

    Interpretationown data

    MyD88 has a role in regulating macrophage signaling on large versus small fiber/pore size PDO scaffolds, and scaffolds of different fiber/pore sizes signal to macrophages differently.

    “This result indicates a potential role for MyD88 in regulating M1 BMMΦ signaling on the large vs. small fiber/pore size PDO scaffold.”
    • Also stated in: § 4. Discussion · hedged
      “The study indicates a potential role for MyD88 in regulating M1 BMMΦ signaling on the large vs. small fiber/pore size PDO scaffold.”
    • Also stated in: § 5. Conclusion · boosted
      “We have also shown that the scaffolds with different fiber/pore sizes signal to the BMMΦs differently and have identified MyD88 to be a key component involved in the signaling mechanism.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Both fiber and pore dimensions increase linearly with polymer concentration.

    “Both fiber and pore dimensions increase linearly with concentration [18].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [18] Boland, 2005, Electrospinning polydioxanone for biomedical applications, Acta Biomater source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Pore size is a crucial property of tissue engineering scaffolds and a key determinant of a scaffold's success through its influence on cell infiltration, nutrient/oxygen exchange and angiogenesis.

    “Pore size has always been a crucial property of tissue engineering scaffolds and a key determinant of a scaffold’s success through their influence on cell infiltration, nutrient/oxygen exchange, and angiogenesis [41, 42].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [41] Yannas, 1989, Synthesis and characterization of a model extracellular matrix that induces partial regeneration of adult mammalian skin, Proc Natl Acad Sci USA source

      Not checked in the free run.

    • cites [42] Dagalakis, 1980, Design of an artificial skin. Part III. Control of pore structure, J Biomed Mater Res source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationown data

    These data are instructive for designing and engineering biomaterials that can promote in situ angiogenesis and tissue regeneration.

    “These data are instructive for the design and engineering of biomaterials that can promote in situ angiogenesis and tissue regeneration.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: An M2 macrophage phenotype promotes healing and integration of the biomaterial with the host tissue, enhancing tissue regeneration.
    • Rests on an assumption: In vitro macrophage responses to scaffold architecture predict in vivo tissue regeneration outcomes.

  • May combine two claims.

    Interpretationown data

    Macrophages of M2 phenotype are functional and can support angiogenesis.

    “we have shown that the BMMΦs of M2 phenotype are functional and can support angiogenesis.”
    • Also stated in: § 5. Conclusion · boosted
      “We further demonstrated that these BMMΦs of M2 phenotype are functional and support angiogenesis”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The 140 mg/ml PDO scaffold signals to M1 macrophages through a MyD88-dependent mechanism, whereas the 60 mg/ml PDO scaffold signals through a MyD88-independent mechanism.

    “The 140 mg/ml PDO scaffold signal to M1s through a MyD88-dependant mechanism whereas, 60 mg/ml PDO scaffold signals through a MyD88-independent mechanism.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Macrophages play a key role in the success and potential failure of any biomaterial.

    “macrophages play a key role in the success and potential failure of any biomaterial”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Greisler et al. [21, 33–36]

      Not checked in the free run.

    • cites Valentin et al. [37] Valentin, 2009, Macrophage participation in the degradation and remodeling of extracellular matrix scaffolds, Tissue Eng Part A source

      Not checked in the free run.

    • cites Brown et al. [4] Brown, 2009, Macrophage phenotype and remodeling outcomes in response to biologic scaffolds with and without a cellular component, Biomaterials source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    M1s are pro-inflammatory and microbicidal; M2s are immunomodulatory, reparative, and poorly microbicidal.

    “In general, M1s or classically activated MΦs are pro-inflammatory and microbicidal, whereas M2s or alternatively activated MΦs are immunomodulatory, reparative, and poorly microbicidal [7–12].”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [7] Fairweather, 2009, Alternatively activated macrophages in infection and autoimmunity, J Autoimmun source

      Not checked in the free run.

    • cites [8] Gordon, 2003, Alternative activation of macrophages, Nat Rev Immunol source

      Not checked in the free run.

    • cites [9] Gordon, 2010, Alternative activation of macrophages: mechanism and functions, Immunity source

      Not checked in the free run.

    • cites [10] Martinez, 2009, Alternative activation of macrophages: an immunologic functional perspective, Annu Rev Immunol source

      Not checked in the free run.

    • cites [11] Varin, 2009, Alternative activation of macrophages: immune function and cellular biology, Immunobiology source

      Not checked in the free run.

    • cites [12] Galli, 2011, Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils, Nat Immunol source

      Not checked in the free run.

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

    Premisecitation

    The grid method has been used in a previous study to quantify migration of sprouts in a 3D matrix.

    “This grid has been used in a previous study to quantify the migration of sprouts in a 3D matrix [29].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [29] Vernon, 1999, A novel, quantitative model for study of endothelial cell migration and sprout formation within three-dimensional collagen matrices, Microvasc Res source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    The results of this study can be extrapolated to predict macrophage responses to other biomaterials.

    “The authors believe that the results of this study can be extrapolated to predict MΦ responses to other biomaterials as well.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: An M2 macrophage phenotype promotes healing and integration of the biomaterial with the host tissue, enhancing tissue regeneration.
    • Rests on an assumption: In vitro macrophage responses to scaffold architecture predict in vivo tissue regeneration outcomes.

  • Classified as probably not a substantial claim.

    Premisecitation

    The pore size, porosity and surface area to volume ratio were measured using a method described by Soliman et al.

    “The pore size, porosity and surface area to volume ratio of the scaffolds was measured using a method described by Soliman et al. [26].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [26] Soliman, 2011, Controlling the porosity of fibrous scaffolds by modulating the fiber diameter and packing density, J Biomed Mater Res A source

      Not checked in the free run.

32 of 32

  • The paper relies on this without support.

    In vitro BMMΦ responses to PDO scaffolds predict in vivo regeneration.

    “These data are instructive for the rationale design of implantable prosthetics designed to promote in situ regeneration.”

  • The paper relies on this without support.

    The differences in BMMΦ response across PDO scaffolds are due to fiber/pore size rather than other scaffold properties.

    “BMMΦ cultured on these scaffolds showed a correlation between increasing fiber/pore size and increased expression of the M2 marker Arginase 1 (Arg1), along with decreased expression of the M1 marker inducible nitric oxide synthase (iNOS).”

  • The paper relies on this without support.

    An M2 macrophage phenotype promotes healing and integration of the biomaterial with the host tissue, enhancing tissue regeneration.

    “Such a functional M2 phenotype is likely to promote healing and integration of the biomaterial with the host tissue to enhance tissue regeneration.”

  • The paper relies on this without support.

    In vitro macrophage responses to scaffold architecture predict in vivo tissue regeneration outcomes.

    “These data are instructive for the design and engineering of biomaterials that can promote in situ angiogenesis and tissue regeneration.”
4 of 4

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?

  • The collection of secreted cytokines creates an anti-proliferative environment, destroys local matrix, and induces tissue reorganization, allowing increased migratory process and improved pathogen clearance.

    “The collection of secreted cytokines creates an anti‐proliferative environment, destroys local matrix, and induces tissue reorganization, which allows for an increased migratory process and improved pathogen clearance.[ 36 ]”

    From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [36]

    The Introduction describes M1 macrophages as secreting pro-inflammatory cytokines, having anti-proliferative functions, and promoting matrix destruction and tissue reorganization that lets them migrate through injured tissue to clear pathogens. It attributes matrix destruction and reorganization to enzymes such as matrix metalloproteinases, however, not to the collection of secreted cytokines as the claim states. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Increased fiber/pore size (0.35 ± 0.2 to 2.8 ± 0.5 μm fiber diameter; 0.96 ± 0.09 to 14.73 ± 0.63 μm pore size) increased expression of M2 marker Arg1 and angiogenic cytokines, VEGF, TGF-β1, and bFGF, while decreasing the M1 marker iNOS.

    “Increased fiber/pore size (0.35 ± 0.2 to 2.8 ± 0.5 µm fiber diameter; 0.96 ± 0.09 to 14.73 ± 0.63 µm pore size) increased expression of M2 marker Arg1 and angiogenic cytokines, VEGF, TGF‐β1, and basic fibroblast growth factor (bFGF), while decreasing the M1 marker iNOS.”

    From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [36]

    Results §§3.4–3.5 report higher Arg1, lower iNOS, and increased secretion of the named growth factors on larger fiber/pore scaffolds. The claim omits important limits: VEGF increased with size in M0 macrophages, but not M1 or M2, and bFGF increases depended on phenotype and day. The exact fiber and pore measurements are not stated in the passages available from our copy (Results §3.1 describes the size trend without those values); page numbers were not provided. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Larger fiber diameter of polydioxanone enhanced M2 macrophage polarization.

    “Garg et al. supported M2 polarization results when using mouse bone marrow‐derived macrophages (BMDMs), showing that larger fiber diameter of polydioxanone‐enhanced M2 macrophage polarization.[ 36 ]”

    From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [36]

    The Discussion reports that mouse bone marrow-derived macrophages became more M2-like on polydioxanone scaffolds with larger fibers and pores. But the Discussion and Results §3.8 say pore size was a more crucial regulator than fiber diameter; the study does not establish that larger fiber diameter alone enhanced M2 polarization. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Predictable angiogenesis can be identified by upregulation and secretion of VEGF by macrophages as seen in the FBR in vitro models.

    “Hence, predictable angiogenesis can be identified by upregulation and secretion of VEGF by macrophages as seen in the FBR in vitro models.[ 36 , 41 ]”

    From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [36]

    Results §3.5 reports increased VEGF production by macrophages on larger-pore scaffolds for the M0 phenotype, and §3.6 reports greater endothelial sprouting with macrophage-conditioned media in an in vitro assay. The paper does not establish VEGF upregulation or secretion as a predictor of angiogenesis in FBR models; §3.6 also attributes sprouting to other growth factors in the conditioned media. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Macrophages exposed to foreign biomaterials take part in fibrous encapsulation, remodeling, and angiogenesis.

    “Macrophages that are exposed to foreign biomaterials take part in various processes, including fibrous encapsulation, remodeling, and angiogenesis.[ 36 ]”

    From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [36]

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.

  • M0 sprout-length fold change has a zero baseline

    Minor

    The paper reports no sprouting for M0-conditioned media from the 60 mg/ml scaffold. A sprout length at 140 mg/ml therefore cannot be described as 200-fold the length at 60 mg/ml.

  • M0 sprout-density fold change has a zero baseline

    Minor

    With no sprouting reported for M0-conditioned media from the 60 mg/ml scaffold, its density of sprouts is zero. The reported 94-fold density comparison against that scaffold is consequently undefined.

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. General chapter <85> bacterial endotoxins test, US pharmacopeia 31-national formulary 26. United States Pharmacopeial Convention, Rockville, MD; 2009.

Cited by

Sorted by citations

Related

Authors
Garg, K., Pullen, N. A., Oskeritzian, C. A., Ryan, J. J., & Bowlin, G. L.
Affiliations
Virginia Commonwealth University (US)
Corresponding author
Bowlin, Gary L.
ORCID
Venue
Biomaterials
Publisher
Elsevier BV
Published
2013-06
Volume
34
Issue
18
Pages
4439-4451
ISSN
0142-9612 (ISSN-L)
DOI
10.1016/j.biomaterials.2013.02.065
PMC
PMC3623371
OpenAlex
W2070438219
Cited by
457
References
43
Citations by year
2026: 28 · 2025: 35 · 2024: 40 · 2023: 35 · 2022: 48 · 2021: 65 · 2020: 55 · 2019: 39 · 2018: 24 · 2017: 26 · 2016: 32 · 2015: 12 · 2014: 17 · 2013: 1
FWCI
7.34
Type
journal article
Language
en
Open access
Licence
Locations
  • Biomaterials (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of General Medical Sciences (K12GM093857)
  • National Institute of Allergy and Infectious Diseases (R01AI059638, R01AI095494)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Electrospun Nanofibers in Biomedical Applications
  • Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
macrophage polarization, M1/M2 macrophages, electrospun scaffolds, fiber diameter, pore size, polydioxanone, bone marrow-derived macrophages, arginase-1, inducible nitric oxide synthase, angiogenic cytokines, vascular endothelial growth factor, TGF-β1, basic fibroblast growth factor, MyD88, scaffold porosity, tissue regeneration
MeSH terms
Animals, Arginase, Bone Marrow Cells, Endotoxins, Macrophages, Mice, Inbred C57BL, Microscopy, Electron, Scanning, Phenotype, Signal Transduction, Porosity, Polydioxanone, Cell Polarity, Culture Media, Conditioned, Neovascularization, Physiologic, Tissue Engineering, Endothelial Cells, Mice, Nitric Oxide Synthase Type II, Myeloid Differentiation Factor 88, Tissue Scaffolds

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