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Cited by 897Tissue Engineering and Regenerative MedicinePancreatic function and diabetesBone Tissue Engineering Materials

Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates

Open access
Veiseh, Omid, Doloff, Joshua C., Ma, Minglin, Vegas, Arturo J., Tam, Hok Hei, Bader, Andrew R., Li, Jie, Langan, Erin +22 more·2015·Nature Materials
DOI 10.1038/nmat4290PMC PMC4477281
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Abstract

The efficacy of implanted biomedical devices is often compromised by host recognition and subsequent foreign body responses. Here, we demonstrate the role of the geometry of implanted materials on their biocompatibility in vivo. In rodent and non-human primate animal models, implanted spheres 1.5 mm and above in diameter across a broad spectrum of materials, including hydrogels, ceramics, metals and plastics, significantly abrogated foreign body reactions and fibrosis when compared with smaller spheres. We also show that for encapsulated rat pancreatic islet cells transplanted into streptozotocin-treated diabetic C57BL/6 mice, islets prepared in 1.5-mm alginate capsules were able to restore blood-glucose control for up to 180 days, a period more than five times longer than for transplanted grafts encapsulated within conventionally sized 0.5-mm alginate capsules. Our findings suggest that the in vivo biocompatibility of biomedical devices can be significantly improved simply by tuning their spherical dimensions.

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Crossref · 10.1038/nmat4290

Cites

51 of 51 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 34 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    At 7 days post-transplantation, a glucose tolerance test showed no significant delays in blood glucose correction kinetics as a function of capsule geometry.

    “At 7 days post-transplantation a glucose tolerance test (GTT) was used to evaluate the kinetics of blood glucose correction and no significant delays were measured as a function of capsule geometry”
    Quote in the paperNot a substantial claim
  • Findingown data

    Western blot analysis showed that α-SMA expression in the cellular overgrowth on alginate spheres significantly decreased as sphere size increased.

    “Western blot analysis of α-SMA expression within the cellular overgrowth on spheres showed a significant decrease as sphere size was increased”
    Quote in the paperSubstantial claim
  • Findingown data

    A multiplexed inflammatory mouse cytokine profile further validated the reduction in innate immune cell accumulation with increasing sphere size.

    “These findings were further validated through a multiplexed inflammatory mouse cytokine profile (Figure 2e).”
    Quote in the paperSubstantial claim
  • Findingown data

    In rodent and non-human primate models, implanted spheres with diameters of 1.5 mm or more, made from a wide range of materials, significantly reduced foreign body reactions and fibrosis relative to smaller spheres.

    “In rodent and non-human primate animal models, implanted spheres 1.5 mm and above in diameter across a broad spectrum of materials, including hydrogels, ceramics, metals, and plastics, significantly abrogated foreign body reactions and fibrosis when compared to smaller spheres.”
    Quote in the paperSubstantial claim
  • Findingown data

    q-PCR expression of Col1a1, Col1a2, and αSMA in rats verified that increasing glass sphere size resulted in a significant reduction of fibrosis formation directly on spheres.

    “q-PCR expression analysis of fibrosis markers, collagen 1a1 (Col1a1), collagen 1a2 (Col1a2), and αSMA, verified that increasing sphere size resulted in a significant reduction of fibrosis formation directly on spheres”
    Quote in the paperSubstantial claim
  • May combine two claims. 19
  • The quote only partly states this claim. 2
  • Classified as probably not a substantial claim. 8

  • May combine two claims.

    Findingown data

    Retrieved 1.5 mm spheres from the NHP intraperitoneal study had minimal cellular deposition, lack of immune macrophages, and fibrosis-associated activated myofibroblast coverage.

    “Z-stacked confocal imaging of the retrieved 1.5 mm spheres confirms minimal cellular deposition, a lack of immune macrophages, and fibrosis-associated activated myofibroblast coverage”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Immunofluorescence showed a significant decrease in macrophage (CD68) and myofibroblast (αSMA) deposition across all materials tested with increased sphere size; large SLG20 alginate, LF10/60, glass, and stainless steel spheres had negligible cellular deposition.

    “Immunofluorescence stained z-stacked confocal images of retrieved materials showed a significant decrease in macrophage (CD68) and myofibroblast (αSMA) deposition across all materials tested, and significantly, large SLG20 alginate, LF10/60 (endotoxin containing alginate), glass, and stainless steel spheres had negligible cellular deposition”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The size-modulated fibrotic deposition effect is not due to delayed kinetics: after 6 months, 1.5 mm SLG20 alginate spheres were largely free of cellular deposition, whereas 0.3 mm spheres were covered with deposited cells and clumped in fibrotic tissue.

    “Dark field phase contrast images from retrieved capsules show that the 1.5 mm spheres are largely devoid of cellular deposition while the 0.3 mm sized spheres are covered with deposited cells and are clumped together in fibrotic tissue”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The size-modulated fibrotic deposition phenomenon extends to other materials: for SLG20 alginate, LF10/60 alginate, stainless steel, glass, polycaprolactone, and polystyrene spheres implanted in C57BL/6 mice, larger spheres (1.5-2.5 mm) had markedly reduced cellular overgrowth thickness compared to medium-sized spheres (0.4-0.6 mm) after 14 days.

    “Bright-field images from retrieved materials 14 days post-implant revealed significant cellular deposition on the medium-sized versions of all materials tested. Interestingly, all materials tested at an increased size led to a marked reduction of the thickness of cellular overgrowth deposition”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In Sprague-Dawley rats, 2.0 mm glass spheres implanted intraperitoneally had no cellular deposition while 0.5 mm spheres were clumped and embedded in a thick fibrotic capsule after 14 days.

    “Bright field and Z-stacked confocal images obtained from retrieved glass microspheres show that the large spheres are devoid of any cellular deposition while the smaller spheres are significantly clumped together and embedded within a thick fibrotic capsule”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In a pilot non-human primate intraperitoneal study, 1.5 mm SLG20 alginate spheres remained translucent and not embedded in omentum/fat tissue after 14 days, while 0.5 mm spheres were embedded in omentum/fat tissue.

    “The obtained in situ images reveal that the 1.5 mm-sized spheres remain translucent and are not embedded into host omentum/fat tissue after 14 days; conversely, the 0.5 mm sized spheres are impeded in to the omentum/fat tissue”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In STZ-induced diabetic C57BL/6 mice transplanted with rat islets, all mice in the 0.5 mm capsule group failed (BG above 200 mg/dl for 3 consecutive measurements) on average by 30 days, while the 1.5 mm capsule group stayed cured on average until 175 days (greater than 5-fold increase) post-transplantation.

    “All mice (n = 5) in the 0.5 mm capsule group failed (i.e. BG above 200 mg/dl for 3 consecutive measurements), on average, by 30 days following transplantation, while in the 1.5 mm capsule group (n = 5), stayed cured, on average, even until 175 days (greater than a 5-fold increase) post-transplantation”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    At 6 months post-transplantation, retrieved 0.5 mm capsules were covered in cellular deposition and clumped, while 1.5 mm capsules were largely clean and void of cellular deposition.

    “Dark field imaging revealed that the 0.5 mm capsules were covered in cellular deposition and clumped but the 1.5 mm capsules were largely clean and void of cellular deposition”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The size-modulated fibrotic response is not merely a function of total surface area: when 0.5 mm and 1.5 mm spheres were implanted with equalized total surface area, the 1.5 mm spheres had limited cellular deposition while the 0.5 mm spheres had significant deposition.

    “To ensure that the size-modulated fibrotic response effect is not simply a function of surface area, we implanted spheres of two sizes, 0.5 mm and 1.5 mm, normalized in total surface area.”
    • Also stated in: § Abstract · plain
      “Dark field phase contrast images of the retrieved spheres revealed only limited cellular deposition on the 1.5 mm-sized spheres and significant cellular deposition on the 0.5 mm sized spheres”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    In C57BL/6 mice, increasing the diameter of implanted Ba+-cross-linked SLG20 alginate hydrogel spheres from 0.3 to 1.9 mm reduced cellular and fibrotic deposition on the spheres after 14 days.

    “Dark field phase contrast images from retrieved spheres show a marked reduction in cellular deposition onto spheres as their size is increased”
    • Also stated in: § Abstract · plain
      “Interestingly, the larger spheres had significantly reduced fibrotic deposition”
    Quote in the paperSubstantial claim

  • May combine two claims. The quote only partly states this claim.

    Findingown data

    In non-human primates, subcutaneously implanted 1.5 mm SLG20 alginate spheres were not embedded in host tissue and had negligible cellular deposition and lack of fibrosis at 14 and 28 days, whereas 0.5 mm spheres and cylinders were profusely embedded in host tissues with fibrosis up to 100 μm thick.

    “At both 14 and 28 days post implantation retrieval time points the 1.5 mm-sized SLG20 alginate spheres were not embedded in host tissue and freely dissociated from the implant site upon incision with a biopsy punch”
    • Also stated in: § Abstract · plain
      “extensive embedding and fibrosis buildup (up to 100 μm thick) is visible enveloping the implanted cylinders and medium sized spheres.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Western blot analysis of retrieved capsules showed that 4 out of 5 mice in the 0.5 mm group had diminished PDX-1 expression and all 5 had high αSMA; all 5 mice in the 1.5 mm group had high PDX-1 and minimal αSMA.

    “4 out of 5 mice in the 0.5 mm capsule group had comparatively diminished PDX-1 expression and all 5 mice showed high levels of alpha smooth muscle expression; conversely, high levels of PDX-1 and minimal alpha smooth muscle actin were detected in capsules retrieved from all 5 mice in the 1.5 mm capsule group”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The wound-healing phenotype marker expression was elevated at day 4 for both sphere sizes and decreased by day 7 for 1.5 mm spheres.

    “This phenotype was elevated at day 4 for both sizes of spheres implanted in mice, and decreased by day 7 for the 1.5 mm-sized spheres.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    On 1.5 mm spheres, neutrophil numbers were negligible and myeloid and macrophage cell numbers were limited at all time points.

    “Notably, on 1.5 mm-sized spheres we observed negligible numbers of neutrophil cells and a limited number of myeloid and macrophage cells at all time points.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In MAFIA mice with induced macrophage depletion, 0.5 mm spheres retrieved after 14 days had limited cellular deposition, whereas non-depleted MAFIA mice had significant cellular deposition.

    “Dark field microscope images of the retrieved spheres revealed only limited cellular deposition onto spheres implanted in mice with depleted macrophages and conversely significant cellular deposition onto spheres received from mice with macrophages (Supplemental Figure S13).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    By four days after implantation, macrophage and neutrophil accumulation was significantly increased on 0.5 mm spheres and appeared to plateau by day 7.

    “In probing macrophage and neutrophil cells, by four days post-implantation we observed significantly increased accumulation on 0.5 mm-sized spheres, which appears to plateau by day 7 (Figure 5b and c).”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Macrophages have remarkable plasticity allowing them to respond to environmental signals and change phenotype.

    “Macrophage cells have remarkable plasticity that allows them to efficiently respond to environmental signals and change their phenotype to address the implicated stimuli43.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [43] Gordon, S. Alternative activation of macrophages. Nature Rev. Immunol. 3, 23–35 (2003). source

      Not checked in the free run.

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

    Study design and conductcitation

    The material spheres evaluated had relatively smooth surfaces, with roughness below 1 μm.

    “The surface roughness of material spheres we evaluated here only included relatively smooth surfaced materials (<1 μm roughness)32, 33.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [32] Lekka, M., Sainz-Serp, D., Kulik, A. J. & Wandrey, C. Hydrogel microspheres: Influence of chemical composition on surface morphology, local elastic properties, and bulk mechanical characteristics. Langmuir 20, 9968–9977 (2004). source

      Not checked in the free run.

    • cites [33] Shellenberger, K. & Logan, B. E. Effect of molecular scale roughness of glass beads on colloidal and bacterial deposition. Environ. Sci. Technol. 36, 184–189 (2002). source

      Not checked in the free run.

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

    Premisecitation

    For materials larger than 100 μm, greater thickness is generally thought to produce proportionally stronger foreign body responses and fibrosis.

    “At the macro level (>100 μm in size), it is generally held that thicker materials produce a proportionally higher magnitude of foreign body responses and fibrosis3, 21.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [3] Nichols, S. P., Koh, A., Storm, W. L., Shin, J. H. & Schoenfisch, M. H. Biocompatible materials for continuous glucose monitoring devices. Chem. Rev. 113, 2528–2549 (2013). source

      Not checked in the free run.

    • cites [21] Helton, K. L., Ratner, B. D. & Wisniewski, N. A. Biomechanics of the sensor-tissue interface-effects of motion, pressure, and design on sensor performance and the foreign body response-part I: Theoretical framework. J. Diabetes Sci. Technol. 5, 632–646 (2011). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Malaga et al. reported that in rat gluteal muscle implants, circular rod cross-sections caused the least foreign body response, then pentagonal, and triangular caused the most.

    “Among the shapes tested, circular rods produced the least amount of foreign body responses followed by pentagonal, and then triangular.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] Matlaga, B. F., Yasenchak, L. P. & Salthouse, T. N. Tissue response to implanted polymers: The significance of sample shape. J. Biomed. Mater. Res. 10, 391–397 (1976). source

      Not checked in the free run.

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

    Premisecitation

    A regulatory macrophage phenotype correlates with elevated expression of IL10, Light, and Sphk1.

    “Meanwhile, a regulatory macrophage phenotype has been characterized to correlate with elevated expression of Interleukin 10 (IL10), TNF superfamily member 14 (Light), and Sphingosine Kinase 1 (Sphk1)44, 45, 46.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [44] Mosser, D. M. & Edwards, J. P. Exploring the full spectrum of macrophage activation. Nature Rev. Immunol. 8, 958–969 (2008). source

      Not checked in the free run.

    • cites [45] Murray, P. J. et al. Macrophage activation and polarization: Nomenclature and experimental guidelines. Immunity 41, 14–20 (2014). source

      Not checked in the free run.

    • cites [46] Gordon, S. & Martinez, F. O. Alternative activation of macrophages: Mechanism and functions. Immunity 32, 593–604 (2010). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Ward et al. reported that larger implanted polyurethane cylinders caused greater foreign body reactions and a thicker fibrotic layer around the implant.

    “They found that increasing the size of implanted materials resulted in larger foreign body reactions, and the formation of a thicker layer of fibrosis around the implant23.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [23] Ward, W. K., Slobodzian, E. P., Tiekotter, K. L. & Wood, M. D. The effect of microgeometry, implant thickness and polyurethane chemistry on the foreign body response to subcutaneous implants. Biomaterials 23, 4185–4192 (2002). source

      Not checked in the free run.

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

    Premisecitation

    The MAFIA model's EGFP transgene enables in situ fluorescent monitoring of macrophages.

    “Furthermore, an EGFP transgene included in this model enables the in situ fluorescent monitoring of macrophage cells42.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] Burnett, S. H. et al. Conditional macrophage ablation in transgenic mice expressing a Fas-based suicide gene. J. Leukocyte Biol. 75, 612–623 (2004). source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Macrophages can be categorized into three activation states: classical/pro-inflammatory, alternative/pro-healing, and regulatory.

    “There is a broad spectrum of macrophage activations which can be categorized into three states namely, classical activation (pro-inflammatory, MClassic), alternative activation (pro-healing, MWound), and regulatory activation (MReg)44.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [44] Mosser, D. M. & Edwards, J. P. Exploring the full spectrum of macrophage activation. Nature Rev. Immunol. 8, 958–969 (2008). source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    A pro-wound healing macrophage phenotype correlates with upregulation of Dcir, Stab1, CCL22, YM1, and Arg1.

    “A pro-wound healing phenotype of macrophage correlates with up regulation in expression of Dendritic Cell Immune Receptor (Dcir), Stabilin 1 (Stab1), chemokine (C-C motif) ligand 22 (CCL22), Chitinase-like 3 (YM1), and Arginase 1 (Arg1)44, 45, 46.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [44] Mosser, D. M. & Edwards, J. P. Exploring the full spectrum of macrophage activation. Nature Rev. Immunol. 8, 958–969 (2008). source

      Not checked in the free run.

    • cites [45] Murray, P. J. et al. Macrophage activation and polarization: Nomenclature and experimental guidelines. Immunity 41, 14–20 (2014). source

      Not checked in the free run.

    • cites [46] Gordon, S. & Martinez, F. O. Alternative activation of macrophages: Mechanism and functions. Immunity 32, 593–604 (2010). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The effect of sphere size on biocompatibility was independent of total implanted surface area and was visible with all materials tested.

    “This effect was demonstrated to be independent of total implanted surface area and visible with all materials tested.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Increasing implant size alone is insufficient to resist foreign body responses; a spherical shape is also integral for resisting host fibrosis/rejection.

    “Further, our finding suggests that simply increasing implant size is insufficient to resist foreign body responses and that a spherical shape is also integral for resisting host fibrosis/rejection.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    A pro-inflammatory macrophage phenotype correlates with elevated expression of TNFα, IL1, and IRF5.

    “A pro-inflammatory macrophage phenotype correlates with elevated expression of Tumor Necrosis Factor α (TNF α), Interleukin 1 (IL1), and Interferon Regulatory Factor 5 (IRF5)44, 45, 46.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [44] Mosser, D. M. & Edwards, J. P. Exploring the full spectrum of macrophage activation. Nature Rev. Immunol. 8, 958–969 (2008). source

      Not checked in the free run.

    • cites [45] Murray, P. J. et al. Macrophage activation and polarization: Nomenclature and experimental guidelines. Immunity 41, 14–20 (2014). source

      Not checked in the free run.

    • cites [46] Gordon, S. & Martinez, F. O. Alternative activation of macrophages: Mechanism and functions. Immunity 32, 593–604 (2010). source

      Not checked in the free run.

28 of 28

  • The paper relies on this without support.

    No prior study has examined the effect of sphere diameter on biocompatibility.

    “Interestingly, to our knowledge no one has studied the effect of sphere diameter on biocompatibility.”

  • The paper relies on this without support.

    Larger 1.5 mm sized spherical capsules have not previously been evaluated for islet cell encapsulation.

    “Thus, to our knowledge larger 1.5 mm sized spherical capsules have previously not been evaluated for islet cell encapsulation.”

  • The paper relies on this without support.

    Findings in rodents and non-human primates about foreign body response to implanted spheres translate to humans.

    “Our findings suggest that the in vivo biocompatibility of biomedical devices can be significantly improved by simply tuning their spherical dimensions.”
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?

  • Smoother implant designs avoiding sharp corners can decrease tissue damage and chronic FBR.

    “Smoother implant designs, avoiding sharp corners which can be particularly damaging to tissue when motion between the two occurs, can also be implemented to decrease tissue damage and chronic FBR (Veiseh et al., 2015).”

    From Foreign Body Reaction to Implanted Biomaterials and Its Impact in Nerve Neuroprosthetics (2021) · cites this paper as Veiseh et al., 2015

    The passage indexed under Abstract says that smooth, well-contoured implants without acute angles are more biocompatible, and the paper reports that implant geometry affects foreign body reactions and fibrosis (page unavailable). It does not establish that sharp corners cause damage specifically when the implant moves against tissue, or that smoothing corners reduces that damage. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Decreasing the size of encapsulation devices down to the scale of individual islet microcapsules increases nutrient diffusion shortly after transplantation compared to macroencapsulation devices, but smaller capsule sizes have also been shown to induce a robust foreign body response and subsequent fibrosis.

    “Interestingly, while decreasing the size of encapsulation devices down to the scale of individual islet microcapsules increases nutrient diffusion shortly after transplantation when compared to macroencapsulation devices, smaller capsule sizes have been shown to also induce a robust foreign body response and subsequent fibrosis.”

    From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [103]

    Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • The size effect was persistent in in vivo mouse, rat, and monkey models, implanting in both subcutaneous and intraperitoneal space, irrespective to the range of materials used, including alginate, stainless steel, glass, PCL, and polystyrene (PS).

    “This extensive study showed observation in size effect to be persistent in in vivo mouse, rat, and monkey models, implanting in both subcutaneous and intraperitoneal space, irrespective to the range of materials used, including alginate, stainless steel, glass, PCL, and polystyrene (PS).”

    From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [122]

  • These size observations are restricted to spherical shapes, as changing the geometry and increasing the biomaterial size provoked in contrast fibrosis or implant rejection.

    “However, these size observations are restricted to spherical shapes, as changing the geometry and increasing the biomaterial size provoked in contrast fibrosis or implant rejection.”

    From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [122]

  • Spheres with a small diameter (≤0.5 mm) induced severe FBR, while large spheres (1.5 mm) scarcely provoked FBR.

    “Veiseh et al. supported this dimension effect, as spheres with a small diameter (≤0.5 mm) induced severe FBR, while large spheres (1.5 mm) scarcely provoked FBR.[ 122 ]”

    From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [122]

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.

  • Conflicting duration of blood-glucose control

    Major

    The 1.5-mm capsule group is described as remaining cured on average until day 175, when the experiment stopped. Later, the paper says mice in that treatment group lost blood-glucose control after approximately 140 days.

  • Figure 4c is assigned to two different results

    Minor

    The text cites Figure 4c for both histology of retrieved primate implants and a glucose-tolerance test of transplanted islets, leaving the panel's identity inconsistent.

2 of 2

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Authors
Veiseh, O., Doloff, J. C., Ma, M., Vegas, A. J., Tam, H. H., Bader, A. R., Li, J., Langan, E., Wyckoff, J., Loo, W. S., Jhunjhunwala, S., Chiu, A., Siebert, S., Tang, K., Hollister-Lock, J., Aresta-Dasilva, S., Bochenek, M., Mendoza-Elias, J., Wang, Y., Qi, M., Lavin, D. M., Chen, M., Dholakia, N., Thakrar, R., Lacík, I., Weir, G. C., Oberholzer, J., Greiner, D. L., Langer, R., & Anderson, D. G.
Affiliations
  • Boston Children's Hospital (US)
  • Koch Institute for Integrative Cancer Research At MIT (US)
  • Massachusetts Institute of Technology (US)
  • University of Illinois Chicago (US)
  • Joslin Diabetes Center (US)
  • University of Massachusetts Chan Medical School (US)
Corresponding author
Anderson, Daniel G.
ORCID
Venue
Nature Materials
Publisher
Springer Science and Business Media LLC
Published
2015-05-18
Volume
14
Issue
6
Pages
643-651
ISSN
  • 1476-1122 (ISSN-L)
  • 1476-4660
DOI
10.1038/nmat4290
PMC
PMC4477281
OpenAlex
W1482515349
Cited by
897
References
51
Citations by year
2026: 63 · 2025: 71 · 2024: 77 · 2023: 79 · 2022: 72 · 2021: 118 · 2020: 107 · 2019: 98 · 2018: 67 · 2017: 69 · 2016: 65 · 2015: 11
FWCI
71.23
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Materials (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship@UMassChan (acceptedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
  • PMC
Funders
  • National Institutes of Health (4r37eb000244-34, 5u54ca119349-05)
  • National Cancer Institute (U54CA151884, CA151884, P30CA014051, P30-CA-14051, U54 CA-119349)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK091526)
  • National Institute of Biomedical Imaging and Bioengineering (EB-000244, R01EB000244, R37-EB000244, EB 000351, R01EB000351)
  • National Institute of Dental and Craniofacial Research (DE013023, R01DE013023)
Topics
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
Keywords
foreign body reaction, biocompatibility, implant geometry, islet transplantation, alginate capsules, streptozotocin-induced diabetes, fibrosis, hydrogels, ceramics, metals, plastics, non-human primates, rodent models
MeSH terms
Animals, Foreign-Body Reaction, Mice, Inbred C57BL, Primates, Mice

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