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Cited by 20Wound Healing and TreatmentsElectrospun Nanofibers in Biomedical ApplicationsTissue Engineering and Regenerative Medicine

Nanosilver alleviates foreign body reaction and facilitates wound repair by regulating macrophage polarization

Open access
You, Chuangang, Zhu, Zhikang, Wang, Shuangshuang, Wang, Xingang, Han, Chunmao, Shao, Huawei·2023·Journal of Zhejiang University SCIENCE B
DOI 10.1631/jzus.b2200447PMC PMC10264175
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Abstract

Foreign body reactions induced by macrophages often cause delay or failure of wound healing in the application of tissue engineering scaffolds. This study explores the application of nanosilver (NAg) to reduce foreign body reactions during scaffold transplantation. An NAg hybrid collagen-chitosan scaffold (NAg-CCS) was prepared using the freeze-drying method. The NAg-CCS was implanted on the back of rats to evaluate the effects on foreign body reactions. Skin tissue samples were collected for histological and immunological evaluation at variable intervals. Miniature pigs were used to assess the effects of NAg on skin wound healing. The wounds were photographed, and tissue samples were collected for molecular biological analysis at different time points post-transplantation. NAg-CCS has a porous structure and the results showed that it could release NAg constantly for two weeks. The NAg-CCS group rarely developed a foreign body reaction, while the blank-CCS group showed granulomas or necrosis in the subcutaneous grafting experiment. Both matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were reduced significantly in the NAg-CCS group. The NAg-CCS group had higher interleukin (IL)-10 and lower IL-6 than the blank CCS group. In the wound healing study, M1 macrophage activation and inflammatory-related proteins (inducible nitric oxide synthase (iNOS), IL-6, and interferon-‍γ (IFN-‍γ)) were inhibited by NAg. In contrast, M2 macrophage activation and proinflammatory proteins (arginase-1, major histocompatibility complex-II (MHC-II), and found in inflammatory zone-1 (FIZZ-1)) were promoted, and this was responsible for suppressing the foreign body responses and accelerating wound healing. In conclusion, dermal scaffolds containing NAg suppressed the foreign body reaction by regulating macrophages and the expression of inflammatory cytokines, thereby promoting wound healing.

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Registry

Crossref · 10.1631/jzus.b2200447

Cites

37 of 37 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

38 of 50 cited sources checked · 4 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    Overactive M1 macrophages can activate M2 macrophages intensively, resulting in a subsequent proliferation of fibrous tissues surrounding the scaffold and aggravating the formation of foreign body granulomas.

    “Besides, overactive M1 macrophages can also activate M2 macrophages intensively, resulting in a subsequent proliferation of fibrous tissues surrounding the scaffold and aggravating the formation of foreign body granulomas (Anderson et al., 2008;Witherel et al., 2021).”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites Anderson et al., 2008 source

      Section 3.1.2 (page unavailable) says alternatively activated macrophages promote fibrogenesis and that biomaterial-adherent macrophages can contribute to a fibrous capsule. Sections 3.1 and 3.2 (pages unavailable) instead describe IL-4 and IL-13 as drivers of alternative activation and foreign body giant-cell formation. The copy does not say overactive M1 macrophages activate M2 macrophages or that this sequence aggravates foreign body granulomas. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites Witherel et al., 2021 source

      The Introduction links both M1- and M2-associated signals to fibrosis, and the Results (Effects of IL4+IL13 release on fibrous capsule properties; page unavailable) report increased matrix deposition around hydrogels given M2-promoting cytokines. But the paper does not show overactive M1 macrophages activating M2 macrophages or establish that this sequence aggravates foreign body granulomas; the reported increase in capsule thickness was only a trend. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
  • Premisecitation

    Uncontrolled infection or inflammation at the early stage of implantation may lead to foreign body reactions and granuloma formation, which suppresses the physiological process of skin wound healing.

    “As a result, uncontrolled infection or inflammation at the early stage of implantation may lead to foreign body reactions and granuloma formation, which suppresses the physiological process of skin wound healing”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites Huang et al., 2018 source
    • cites Benayahu et al., 2020 source

      The Results (§2; page not provided) describe inflammatory cells and giant cells as an expected response to the implanted material. The paper does not say that uncontrolled early infection or inflammation causes granulomas or suppresses skin wound healing; its Discussion (§3) instead describes the observed response as part of healing. Its reference to granulation tissue is not evidence of granuloma formation. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
  • Premisecitation

    Our previous studies demonstrated that NAg-CCS was favorable and applicable for treating burn wounds.

    “Our previous studies demonstrated that nanosilver (NAg)-loaded collagen-chitosan scaffold (NAg-CCS) was favorable and applicable for treating burn wounds.”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites You et al., 2012 source

      The Wound therapy section (page unavailable) says silver-nanoparticle dressings may reduce infection and accelerate healing in second-degree burns. It discusses other silver-containing scaffolds, but does not identify or report findings for the specific nanosilver-loaded collagen-chitosan scaffold (NAg-CCS), so it cannot establish that prior studies found NAg-CCS favorable for treating burns. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
    • cites You et al., 2017 source

      The Results section reports faster epithelialization and smaller residual wound areas with NAg-CCS than with CCS. However, the Methods describe surgically excised full-thickness wounds in rats, not burn wounds. The study supports NAg-CCS as promising for wound healing, but does not demonstrate its applicability specifically to burns. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
  • Premisecitation

    Macrophages and giant cells are activated and accumulate when medical devices, prostheses, or biomaterials are implanted.

    “Macrophages and giant cells will be activated and initiated to accumulate when medical devices, prostheses, or biomaterials are implanted”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Sheikh et al., 2015 source
  • Premisecitation

    Apart from antimicrobial effects, NAg-loaded scaffolds can also inhibit the abnormal inflammatory response effectively.

    “Apart from their antimicrobial effects, NAg-loaded scaffolds can also inhibit the abnormal inflammatory response effectively”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites You et al., 2012 source

      The Anti-inflammatory uses section reports that nano-crystalline silver dressings may aid wound healing through anti-inflammatory activity and that silver cream suppresses inflammatory markers. The Wound therapy section reports antibacterial effects for silver-loaded scaffolds, but does not show that those scaffolds effectively inhibit an abnormal inflammatory response. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites You et al., 2017 source
  • Classified as probably not a substantial claim. 9
  • May combine two claims. 29

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

    Premisecitation

    As foreign bodies, successful implantations of tissue engineering products should overcome two obstacles: infection and foreign body reactions.

    “However, as foreign bodies, successful implantations of these products should overcome two obstacles: infection and foreign body reactions”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Weng et al., 2020 source

      The Introduction (page unavailable) says skin-replacement biomaterials must protect wounds from infection, supporting one of the two stated obstacles. The passages on scaffold requirements and challenges do not identify foreign body reactions as an obstacle to implantation. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

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

    Premisecitation

    iNOS is an intermediate metabolite of activated M1 macrophages involved in antibacterial-related biological processes.

    “iNOS is an intermediate metabolite of activated M1 macrophages involved in antibacterial-related biological processes (Orecchioni et al., 2019;Paul et al., 2019).”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites Orecchioni et al., 2019 source

      The “In vivo M1 and in vitro Classically Activated Mφ Common Pathways” section says iNOS signaling is enriched and is a main bacterial-killing pathway in these macrophages. The “In vivo and in vitro M1 Signatures” section identifies iNos (Nos2) as a gene, not an intermediate metabolite; that characterization is unsupported. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites Paul et al., 2019 source

      The Introduction (page not supplied) says M1 macrophages produce iNOS, and the Results (page not supplied) use iNOS as a marker of M1 macrophages. The paper identifies iNOS as inducible nitric oxide synthase, not an intermediate metabolite, and the cited passages concern anti-tumor immunity rather than antibacterial processes. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    In the absence of NAg, long-term abnormal inflammation of the wound tissue may occur resulting in granulomas, infection, or necrosis, eventually leading to the failure of tissue repair.

    “Hence, in the absence of NAg, long-term abnormal inflammation of the wound tissue may occur resulting in granulomas, infection, or necrosis, eventually leading to the failure of tissue repair (Chu et al., 2020;Witherel et al., 2021).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites Chu et al., 2020 source
    • cites Witherel et al., 2021 source

      The Introduction (page not provided) says that fibrosis can occur when wound healing fails to resolve, supporting the general link between unresolved healing and pathological tissue changes. It does not address the absence of NAg or say that prolonged inflammation causes granulomas, infection, or necrosis leading to failed repair. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

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

    Premisecitation

    Wound healing of burns and trauma is compromised by various unfavorable factors, the most common of which are wound infection and an abnormal inflammatory response.

    “Wound healing of burns and trauma is compromised by various unfavorable factors, the most common of which are wound infection and an abnormal inflammatory response”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites Shi et al., 2020 source

      The Burns section says infection can worsen superficial and partial-thickness burns, and that increasing exudate during the inflammatory phase can delay healing. It does not identify an abnormal inflammatory response as a cause or establish infection and that response as the most common factors compromising healing of burns and trauma. Page numbers are unavailable in our copy. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites Yang et al., 2021 source

      The Introduction says excessive inflammation and bacterial colonization can prolong healing in diabetic wounds; the Anti-inflammation evaluation likewise calls increased inflammation a major cause of prolonged wound closure in diabetic patients. These passages support the general concern, but they do not establish it specifically for burns and trauma or show that infection and abnormal inflammation are the most common unfavorable factors in those wounds. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

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

    Premisecitation

    M1 and M2 macrophages play coordinating roles in the wound healing process by secreting cytokines such as IL-6, TGF-β, TNF-α, and IL-8 to mobilize peripheral or systemic monocytes and lymphocytes to gather around the wound surface.

    “M1 and M2 macrophages also play coordinating roles in the wound healing process by secreting cytokines, such as IL-6, transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α), and IL-8, to mobilize peripheral or systemic monocytes and lymphocytes to gather around the wound surface (Snyder et al., 2016;Wynn and Vannella, 2016).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Snyder et al., 2016 source
    • cites Wynn and Vannella, 2016 source

      The Introduction (page unavailable) says macrophages of different phenotypes regulate stages of wound repair and produce inflammatory mediators; it also identifies TGF-β1 as a product of wound-healing macrophages. The Tissue Regeneration section (page unavailable) describes TNF-α-producing inflammatory macrophages, but says CCL2 from neighboring hair follicles recruits them. These passages do not support the specific claim that macrophage-secreted IL-6, TGF-β, TNF-α, and IL-8 mobilize monocytes and lymphocytes to the wound surface. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Activation of M2 macrophages at an earlier stage led to faster matrix synthesis and deposition around the implant, reduced the foreign body reaction caused by inflammatory activation, and enabled the healing process to shift from the inflammatory phase to the proliferative phase more quickly, achieving complete wound healing and reducing scar formation.

    “Activation of M2 macrophages at an earlier stage led to faster matrix synthesis and deposition around the implant (Li and Cui, 2021;Furtado et al., 2022), reduced the foreign body reaction caused by inflammatory activation, and enabled the healing process to shift from the inflammatory phase to the proliferative phase more quickly, achieving complete wound healing and reducing scar formation.”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites Li and Cui, 2021 source

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

      Experimental — accuracy not yet measured
    • cites Furtado et al., 2022 source

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

      Experimental — accuracy not yet measured

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

    Premisecitation

    IFN-γ and TNF-α induce activation of M1 macrophages to trigger a respiratory burst, release reactive oxygen species, secrete TNF-α and IL-12, induce iNOS, and upregulate expression of programmed death-ligand 1 (PD-L1).

    “IFN-γ and TNF-α induce activation of Ml macrophages to trigger a respiratory burst, release reactive oxygen species, secrete TNF-α and IL-12, induce iNOS, and upregulate expression of programmed death-ligand 1 (PD-L1) (Jain and Vogel, 2018;Tan et al., 2019).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Jain and Vogel, 2018 source

      The Methods (Macrophage activation; page not provided) use LPS, not IFN-γ and TNF-α, to induce M1 activation. The sections on late pro-inflammatory gene expression and cytokine secretion report iNOS expression and secretion of TNF-α and IL-12 after LPS stimulation. Our copy does not establish the claimed respiratory burst, reactive oxygen species release, or PD-L1 upregulation. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites Tan et al., 2019 source

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

    Premisecitation

    M2 macrophages are induced by IL-4 and IL-13 to upregulate IL-10 and FIZZ-1 and secrete less IL-12 and nitric oxide, weakening the phagocytosis of pathogenic microorganisms.

    “M2 macrophages are induced by IL-4 and IL-13 to upregulate IL-10 and FIZZ-1 and secrete less IL-12 and nitric oxide, weakening the phagocytosis of pathogenic microorganisms (Locati et al., 2020;Yunna et al., 2020;Witherel et al., 2021).”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites Locati et al., 2020 source

      The sections on macrophage plasticity and adaptation to the tumor microenvironment (pages unavailable) identify IL-4 and IL-13 as drivers of M2 or M2-like activation. The post-transcriptional-control section reports reduced iNOS and IL-12 alongside M2 markers in a specific microRNA-related context. Our copy does not establish the claimed IL-10 and FIZZ-1 upregulation or that these changes weaken phagocytosis of pathogenic microorganisms. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites Yunna et al., 2020 source
    • cites Witherel et al., 2021 source

      The Results (Preparation of hybrid macrophage phenotypes) and Discussion say that IL-4 and IL-13 promote M2 polarization. The paper does not report the claimed increase in IL-10 and FIZZ-1, decrease in IL-12 and nitric oxide, or weakened phagocytosis of pathogens. The Discussion instead distinguishes IL-10-stimulated M2c macrophages from the IL-4/IL-13-stimulated M2a phenotype studied here. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Interpretationown data

    NAg-CCS inhibited the inflammatory response to foreign bodies and promoted high-quality tissue repair.

    “These results indicated that NAg-CCS inhibited the inflammatory response to foreign bodies and promoted high-quality tissue repair (You et al., 2017).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites You et al., 2017 source

  • May combine two claims.

    Findingown data

    NAg was evenly distributed and tightly combined with the collagen in the NAg-CCS.

    “The NAg was evenly distributed and tightly combined with the collagen”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the rat subcutaneous implantation, the NAg-CCS group rarely developed a foreign body reaction, while the blank-CCS group showed granulomas or necrosis.

    “The NAg-CCS group rarely developed a foreign body reaction, while the blank-CCS group showed granulomas or necrosis in the subcutaneous grafting experiment.”
    • Also stated in: § 3.2 Subcutaneous implantation of scaffolds in rats · plain
      “In the NAg-CCS group, no foreign body reaction was observed around the scaffolds”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The blank CCS and NAg-CCS differ only in the presence of NAg, so observed differences are attributable to NAg.

  • May combine two claims.

    Findingown data

    In the miniature pig wound model, wound healing of the NAg-CCS group was faster and better than that of the blank CCS group.

    “They show that the wound healing of the NAg-CCS group was faster and better than that of the blank CCS group”
    • Also stated in: § 3.4 Wound repair experiment in miniature pigs · plain
      “Calculation of the wound area at different time points after implantation confirmed that the wound healing rate of the NAg-CCS group was significantly faster than that of the blank CCS group”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The blank CCS and NAg-CCS differ only in the presence of NAg, so observed differences are attributable to NAg.
    • Rests on an assumption: The rat subcutaneous implantation model and miniature pig wound model are adequate to predict the effects of NAg-CCS on foreign body reaction and wound healing in humans.

  • May combine two claims.

    Findingown data

    In the rat subcutaneous implantation, the NAg-CCS group had fewer multinucleated giant cells and more orderly tissue growth than the blank CCS group.

    “The NAg-CCS group had fewer multinucleated giant cells and the tissue grew in a more orderly manner”
    Quote in the paperSubstantial claim

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

    Findingown data

    NAg-CCS has a porous, sponge-like structure.

    “NAg-CCS has a porous structure”
    • Also stated in: § 3.1 Construction and characterization of NAg-CCS · plain
      “They were slightly yellow, with hollow and sponge-like structures inside the scaffold.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The blank CCS with a mixture of NAg released 50% of NAg on Day 2, while no sudden release was observed in the NAg-CCS group.

    “The release study revealed that the blank CCS with a mixture of NAg released 50% of NAg on Day 2, while no sudden release was observed in the NAg-CCS group”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The cumulative release of NAg from NAg-CCS was (80.45±1.70)%, slightly lower than that of the blank CCS group ((90.78±5.21)%).

    “the cumulative release of NAg was (80.45±1.70)%, which was slightly lower than that of the blank CCS group ((90.78±5.21)%).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the miniature pig wound model, on postoperative Day 7, the NAg-CCS group wound was red and moist, while the blank CCS group wound failed to combine tightly with little substantial neovascularization.

    “On postoperative Day 7, the wound of the NAg-CCS group was red and moist, while the wound and blank CCS failed to combine tightly in the blank CCS group, with little substantial neovascularization on the wound base.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the miniature pig wound model, in the NAg-CCS group, the scaffold structure was degraded and there was flocculent secretion of new collagen at the base on postoperative Day 7.

    “In the NAg-CCS group, the scaffold structure was degraded, and there was a flocculent secretion of new collagen at the base on postoperative Day 7.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the miniature pig wound model, on postoperative Day 14, inflammation in the blank-CCS group was still pronounced without evident epithelialization, while inflammatory cell infiltration in the NAg-CCS group was significantly reduced compared with Day 7.

    “On postoperative Day 14, inflammation in the blank-CCS group was still pronounced, without showing evident epithelialization; in contrast, the infiltration of inflammatory cells in the NAg-CCS group was significantly reduced compared with that on postoperative Day 7.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the miniature pig wound model, HE staining on Day 7 showed the NAg-CCS scaffolds were replaced by new granulation tissues, while residual scaffolds in the blank CCS group were distinguishable with hyperemia, loose tissues, and gaps.

    “HE staining (Fig. 4d) showed that on Day 7, the scaffolds of the NAg-CCS group had been replaced by new granulation tissues, while the residual scaffolds in the blank CCS group were easily distinguishable from the surrounding tissues, showing hyperemia, loose tissues, and gaps.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the miniature pig wound model, by the third week after implantation, collagen deposition in the NAg-CCS group was reduced, while the blank CCS group still had numerous collagen depositions showing as globular forms.

    “By the third week after implantation, the collagen deposition of the NAg-CCS group was reduced, while the blank CCS group still had numerous collagen depositions, showing as globular forms.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the miniature pig wound model, on postoperative Day 14, newly formed collagen in the NAg-CCS group was staggered, and the inflammatory response was gradually reducing.

    “In contrast, the newly formed collagen in the NAg-CCS group was staggered, and the inflammatory response of the NAg-CCS group was gradually reducing.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the miniature pig wound model, on postoperative Day 14, the blank CCS group still had degraded collagen particles and newly formed collagen was disordered.

    “On postoperative Day 14, the blank CCS group still had degraded collagen particles, and the newly formed collagen was disordered.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the miniature pig wound model, on postoperative Day 28, collagen in the blank CCS group was distributed unidirectionally in bundles, while collagen in the NAg-CCS group was distributed in a staggered pattern.

    “On postoperative Day 28, unidirectional distribution of collagen in bundles was observed in the blank CCS group, while the collagen in the NAg-CCS group was distributed in a staggered pattern.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the miniature pig wound model, on postoperative Day 60, skin repaired by NAg-CCS had an epidermis and dermis with mature and complete skin appendages, while the blank CCS group had a disordered skin tissue structure.

    “On postoperative Day 60, the skin repaired by the NAg-CCS had an epidermis and dermis, with mature and complete skin appendages; in contrast, the blank CCS group had a disordered skin tissue structure.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the wound healing study, M2 macrophage activation and proteins (arginase-1, MHC-II, FIZZ-1) were promoted by NAg.

    “In contrast, M2 macrophage activation and proinflammatory proteins (arginase-1, major histocompatibility complex-II (MHC-II), and found in inflammatory zone-1 (FIZZ-1)) were promoted”
    Quote in the paperSubstantial claim
    • Rests on an assumption: IL-6 and IL-10 are valid markers of M1 and M2 macrophages in this model.

  • May combine two claims.

    Findingown data

    In the miniature pig wound model, in the early stage, the regenerated dermis of both groups was thin; the blank CCS group still had a visible undegraded scaffold surrounded by many inflammatory cells and blood cells.

    “In the early stage, the regenerated dermis of the two groups was thin; the blank CCS group still had a visible undegraded scaffold, which was blue-gray and was surrounded by many inflammatory cells and blood cells.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the miniature pig wound model, collagen regeneration of the NAg-CCS group was stable and orderly, with uniform collagen distribution.

    “The collagen regeneration of the NAg-CCS group was stable and orderly, and collagen distribution was uniform”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The inflammatory response of the NAg-CCS group was gradually alleviated, and the newly formed collagen in the NAg-CCS group was staggered, almost resembling normal skin on postoperative Days 21 and 28.

    “Additionally, the inflammatory response of the NAg-CCS group was gradually alleviated, and the newly formed collagen in the NAg-CCS group was staggered, almost resembling normal skin on postoperative Days 21 and 28.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Dermal scaffolds containing NAg suppressed the foreign body reaction by regulating macrophages and the expression of inflammatory cytokines, thereby promoting wound healing.

    “In conclusion, dermal scaffolds containing NAg suppressed the foreign body reaction by regulating macrophages and the expression of inflammatory cytokines, thereby promoting wound healing.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: NAg is released from NAg-CCS in vivo in a manner similar to the in vitro release profile.
    • Rests on an assumption: The blank CCS and NAg-CCS differ only in the presence of NAg, so observed differences are attributable to NAg.
    • Rests on an assumption: IL-6 and IL-10 are valid markers of M1 and M2 macrophages in this model.
    • Rests on an assumption: In wound repair, M1 and M2 macrophages are sequentially activated, with M1 early and M2 in the middle stage.
    • Rests on an assumption: The rat subcutaneous implantation model and miniature pig wound model are adequate to predict the effects of NAg-CCS on foreign body reaction and wound healing in humans.

  • May combine two claims.

    Interpretationreasoning

    The promotion of M2 macrophage activation and proteins was responsible for suppressing foreign body responses and accelerating wound healing.

    “and this was responsible for suppressing the foreign body responses and accelerating wound healing.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: IL-6 and IL-10 are valid markers of M1 and M2 macrophages in this model.
    • Rests on an assumption: In wound repair, M1 and M2 macrophages are sequentially activated, with M1 early and M2 in the middle stage.

  • May combine two claims.

    Interpretationreasoning

    NAg ameliorated the foreign body reaction after scaffold implantation and reduced the infiltration of giant cells and inflammatory cells around the scaffolds in the early stage.

    “This indicated that NAg ameliorated the foreign body reaction after scaffold implantation and reduced the infiltration of giant cells and inflammatory cells around the scaffolds in the early stage.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Inflammation plays a dominant role in necrosis elimination, pathogen suppression, and regulation of the immune microenvironment.

    “Inflammation, as an important component present throughout the whole period of wound repair, plays a dominant role in necrosis elimination, pathogen suppression, and regulation of the immune microenvironment”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Bergan, 2005 source
    • cites Forbes and Cooper, 2013 source
    • cites Wicks et al., 2014 source

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

    Study design and conductnone given

    Experiments were approved and supervised by the Animal Care and Ethical Committee of the Second Affiliated Hospital of Zhejiang University (No. 2020-720).

    “Experiments were approved and supervised by the Animal Care and Ethical Committee of the Second Affiliated Hospital of Zhejiang University (No. 2020-720).”
    Quote in the paperNot a substantial claim
34 of 34

  • The paper relies on this without support.

    NAg is released from NAg-CCS in vivo in a manner similar to the in vitro release profile.

    “The NAg-CCS group showed a slow release of NAg within two weeks”

  • The paper relies on this without support.

    The blank CCS and NAg-CCS differ only in the presence of NAg, so observed differences are attributable to NAg.

    “followed by subcutaneous implantation of an NAg-CCS (one on one side and the blank CCS on the other side).”

  • The paper relies on this without support.

    IL-6 and IL-10 are valid markers of M1 and M2 macrophages in this model.

    “the number of IL-6-positive cells (M1 macrophages) on Days 3 and 7 after scaffold implantation in the NAg-CCS group was much lower than that in the blank CCS group”
    “the number of IL-10-positive cells (M2 macrophages) on Day 3 after scaffold implantation in the NAg-CCS group was not significantly different from that of the blank CCS group”

  • The paper relies on this without support.

    In wound repair, M1 and M2 macrophages are sequentially activated, with M1 early and M2 in the middle stage.

    “In the process of wound repair, two types of macrophages are sequentially activated.As a scavenger, M1 macrophages participate in antiinfection and the formation of foreign-body giant cells at the early stage, whereas M2 macrophages are involved mainly in the middle stage of wound repair.”

  • The paper relies on this without support.

    The rat subcutaneous implantation model and miniature pig wound model are adequate to predict the effects of NAg-CCS on foreign body reaction and wound healing in humans.

    “The NAg-CCS was implanted on the back of rats to evaluate the effects on foreign body reactions.”
    “Miniature pigs were used to assess the effects of NAg on skin wound healing.”
5 of 5

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.

  • A collagen finding cites a macrophage-marker panel

    Minor

    The discussion cites Fig. 6b for collagen I and III content, but the caption identifies that panel as western blots of CD163 and CD68.

  • The same markers are classified as both pro- and anti-inflammatory

    Minor

    The abstract calls arginase-1, MHC-II, and FIZZ-1 proinflammatory, whereas the results classify the same three markers as anti-inflammatory.

  • The control scaffold's 50% silver release is dated differently

    Minor

    The results place the control's approximately 50% release on Day 2, while the Fig. 1 caption places the sudden release on Day 1.

3 of 3

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Authors
You, C., Zhu, Z., Wang, S., Wang, X., Han, C., & Shao, H.
Affiliations
  • Second Affiliated Hospital of Zhejiang University (CN)
  • The First People's Hospital of Wenling (CN)
Corresponding author
  • Han, Chunmao
  • Shao, Huawei
ORCID
Venue
Journal of Zhejiang University SCIENCE B
Publisher
Zhejiang University Press
Published
2023-06
Volume
24
Issue
6
Pages
510-523
ISSN
  • 1673-1581 (ISSN-L)
  • 1862-1783
DOI
10.1631/jzus.b2200447
PMC
PMC10264175
OpenAlex
W4380422883
Cited by
20
References
37
Citations by year
2026: 7 · 2025: 6 · 2024: 7
FWCI
2.19
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Zhejiang University SCIENCE B (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (81601681 and 81871558, 81601681, 81871558)
Topics
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
  • Physical Sciences › Materials Science › Biomaterials › Electrospun Nanofibers in Biomedical Applications
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
silver nanoparticles, foreign body reaction, wound healing, macrophage polarization, collagen-chitosan scaffold, tissue engineering scaffolds, M1/M2 macrophage balance, arginase-1, subcutaneous implantation, silver release
MeSH terms
Animals, Foreign Bodies, Foreign-Body Reaction, Macrophage Activation, Silver, Swine, Wound Healing, Interleukin-6, Tissue Inhibitor of Metalloproteinase-1, Chitosan, Rats

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 2026-10-11.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-11.

Cited sources are checked by gpt-6-sol.

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.

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