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Cited by 98Bone Tissue Engineering Materialsbiodegradable polymer synthesis and propertiesHydrogels: synthesis, properties, applications

Resorbable Biomaterials Used for 3D Scaffolds in Tissue Engineering: A Review

Open access
Vach Agocsova, Sara, Culenova, Martina, Birova, Ivana, Omanikova, Leona, Moncmanova, Barbora, Danisovic, Lubos, Ziaran, Stanislav, Bakos, Dusan +1 more·2023·Materials
DOI 10.3390/ma16124267PMC PMC10301242
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Abstract

This article provides a thorough overview of the available resorbable biomaterials appropriate for producing replacements for damaged tissues. In addition, their various properties and application possibilities are discussed as well. Biomaterials are fundamental components in tissue engineering (TE) of scaffolds and play a critical role. They need to exhibit biocompatibility, bioactivity, biodegradability, and non-toxicity, to ensure their ability to function effectively with an appropriate host response. With ongoing research and advancements in biomaterials for medical implants, the objective of this review is to explore recently developed implantable scaffold materials for various tissues. The categorization of biomaterials in this paper includes fossil-based materials (e.g., PCL, PVA, PU, PEG, and PPF), natural or bio-based materials (e.g., HA, PLA, PHB, PHBV, chitosan, fibrin, collagen, starch, and hydrogels), and hybrid biomaterials (e.g., PCL/PLA, PCL/PEG, PLA/PEG, PLA/PHB PCL/collagen, PCL/chitosan, PCL/starch, and PLA/bioceramics). The application of these biomaterials in both hard and soft TE is considered, with a particular focus on their physicochemical, mechanical, and biological properties. Furthermore, the interactions between scaffolds and the host immune system in the context of scaffold-driven tissue regeneration are discussed. Additionally, the article briefly mentions the concept of in situ TE, which leverages the self-renewal capacities of affected tissues and highlights the crucial role played by biopolymer-based scaffolds in this strategy.

AI snapshot

Written from the paper’s full text.

TL;DR

This review surveys resorbable biomaterials for 3D tissue-engineering scaffolds, grouping them into fossil-based, natural/bio-based, and hybrid categories and comparing their physicochemical, mechanical, and biological properties. It also discusses scaffold–host immune interactions and in situ TE, concluding that hybrid materials and immunomodulatory design are promising but many formulations remain unoptimized for clinical translation.

Key findings

  • The review classifies scaffold biomaterials into fossil-based polymers (PCL, PVA, PU, PEG, PPF), natural/bio-based materials (HA, PLA, PHB, PHBV, chitosan, fibrin, collagen, starch, hydrogels), and hybrid biomaterials (e.g., PCL/PLA, PCL/PEG, PLA/PEG, PLA/PHB, PCL/collagen, PCL/chitosan, PCL/starch, PLA/bioceramics).
  • Reported scaffold design parameters include PCL porosity >90% for degradation control and cell attachment; PLA ideal pore diameter 100–300 μm with micropores 10–60 μm promoting cell proliferation; HA hydrogel pore size 200–250 μm supporting best cell proliferation and 3D migration; fibrin scaffold pores 0–35.86 µm and 35.86–89.65 µm with total porosity 43.28%; starch porosity: 6–8 μm voids ~20%, 1–35 μm voids ~60%, very small pores 10%, remaining 10% possibly >150 μm.
  • Immune response findings: biological scaffolds induced type-2 immune response with high CD206 (M2) expression and Th2-associated genes, while fossil-based scaffolds caused chronic inflammation with neutrophil infiltration and M2 antigen depletion; aligned larger-diameter fibers favored M2 polarization, and larger pore size had pro-regenerative effects.
  • Hybrid biomaterials are presented as a way to overcome individual material limitations; PLA/PHB 3D-printed objects showed favorable mechanical properties, thermal stability, and cell viability but lacked the porous structure needed for TE, and in situ TE is described as using cell-free bioactive scaffolds to trigger endogenous repair.

Methods

  • Narrative literature review; no primary experimental data, sample, or systematic search protocol reported.
  • The paper categorizes biomaterials and discusses their physicochemical, mechanical, and biological properties, applications in hard and soft TE, and interactions with the host immune system.
  • It also briefly covers in situ TE and biopolymer-based scaffolds, drawing on cited studies rather than performing meta-analysis.

Limitations

  • The paper states that many materials have not been fully optimized for particular TE applications and further work is needed for clinical translation; fabricating an ideal scaffold fulfilling all desired properties remains a challenge.
  • The paper notes that natural polymer degradation cannot be precisely controlled, leading to mismatch between scaffold degradation and new tissue formation; PLA/PHB scaffolds lack the porous structure necessary for TE and require more research.
  • Evident from the text: as a narrative review, it does not report a systematic search strategy, inclusion/exclusion criteria, or quantitative synthesis, so conclusions depend on selected cited studies.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3390/ma16124267

Cites

229 of 229 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

83 of 256 cited sources checked · 30 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    Fossil-based polymers can provide better control over the synthesis and design of the polymer itself.

    “They usually have a controlled structure, no immunological reaction, and a higher degree of processing flexibility. They can also provide better control over the synthesis and design of the polymer itself [11].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [11] Guo, 2014, Synthetic biodegradable functional polymers for tissue engineering: A brief review, Sci. China Chem. source

      Section 2.1 describes synthetic polymers as having controlled structures and explains that their composition and properties can be tuned, supporting the point about control over polymer design. It does not identify these polymers as fossil-based or establish that the advantage applies specifically to fossil-based polymers. Page numbers are unavailable in our copy. (LLM, conf=0.83)

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  • Premisecitation

    In spinal cord repair, freeze-drying technology has made it possible to produce porous structures quickly and easily.

    “In the realm of spinal cord repair, freeze-drying technology has made it possible to produce porous structures quickly and easily [69].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [69] 2017, (Chitosan-g-glycidyl methacrylate)-xanthan hydrogel implant in Wistar rats for spinal cord regeneration, Mater. Sci. Eng. C source

      The available indexed passages identify the paper as a study of a hydrogel implant for spinal cord regeneration, but contain no discussion of how porous structures were produced. Searches for freeze-drying, lyophilization, and porous hydrogel preparation returned only bibliographic material, so the claimed ease and speed of production cannot be verified from our copy. (LLM, conf=0.72)

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  • Premisecitation

    Polymers have successfully found applications in the regeneration of muscles, tendons, heart valves, arteries, bladder, and pancreas.

    “Furthermore, they have successfully found applications in the regeneration of muscles, tendons, heart valves, arteries, bladder, and pancreas [10].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [10] Nikolova, 2019, Recent advances in biomaterials for 3D scaffolds: A review, Bioact. Mater. source
  • Premisecitation

    PLA blending with other bio-based materials or fossil-based polymers with better wettability and faster bioresorbability provides an effective solution to modulate its biodegradability, with respect to the time required for tissue growth and regeneration.

    “PLA blending with other bio-based materials or FBP with better wettability and faster bioresorbability provides an effective solution to modulate its biodegradability, with respect to the time required for tissue growth and regeneration [91].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [91] Ritz, U., Gerke, R., Götz, H., Stein, S., and Rommens, P.M. (2017). A new bone substitute developed from 3D-prints of polylactide (PLA) loaded with collagen i: An In Vitro study. Int. J. Mol. Sci., 18. source

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

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  • Premisecitation

    Tubular PHB textiles are used to promote tissue healing in large vessels and hollow organs.

    “Tubular PHB textiles are also used to promote tissue healing in large vessels and hollow organs [97].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [97] Ravi, 2009, Polymeric Materials for Tissue Engineering of Arterial Substitutes, Vascular source

      The Degradable Polymers as Scaffolds section describes PGA/polyhydroxyoctanoate aortic grafts and a PGA/poly-4-hydroxybutyrate construct, not tubular PHB textiles. Searches for PHB textiles and hollow-organ applications found no passage addressing their claimed use; the relevant passages have no page numbers in our copy. (LLM, conf=0.75)

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  • Classified as probably not a substantial claim. 50
  • May combine two claims. 80
  • The quote only partly states this claim. 1

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

    Premisecitation

    Natural polymers are obtained from natural materials and provide a guarantee of natural structure, biomimetic and bioactive nature.

    “Natural polymers (biopolymers) are obtained from natural materials and provide a guarantee of natural structure, biomimetic and bioactive nature [42].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [42] Liu, F., Chen, Q., Liu, C., Ao, Q., Tian, X., Fan, J., Tong, H., and Wang, X. (2018). Natural Polymers for Organ 3D Bioprinting. Polymers, 10. source

      Section 2, “Properties of Natural Polymers” (page unavailable), says natural polymers occur in nature and that their solutions or hydrogels can provide a mild biomimetic environment and facilitate cellular activities. It does not say that natural origin guarantees a natural structure or that every natural polymer is inherently biomimetic and bioactive. (LLM, conf=0.87)

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

    Premisecitation

    Type I collagen is the quantitatively predominant fibrillar collagen in vertebrates.

    “Type I is the quantitatively predominant fibrillar collagen in vertebrates [52].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [52] Siadat, 2023, Mechanochemistry of collagen, Acta Biomater. source

  • May combine two claims.

    Premisecitation

    Scaffolds can be engineered with bio-based and fossil-based polymers, or with bio-based ceramics with suitable combinations.

    “Scaffolds can be engineered with bio-based and fossil-based polymers, or with bio-based ceramics with suitable combinations [9].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [9] Reddy, M.S.B., Ponnamma, D., Choudhary, R., and Sadasivuni, K.K. (2021). A comparative review of natural and synthetic biopolymer composite scaffolds. Polymers, 13. source

      Section 2, “Scaffolding and Its Importance in Biomedical Applications,” says scaffolds can be made with natural or synthetic polymers, bio-based ceramics, or suitable combinations. It does not specify that the synthetic polymers are fossil-based; that material origin is not established by the passage. (LLM, conf=0.86)

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    Premisecitation

    Chitosan is poorly soluble in water under physiological conditions, which limits its widespread use in tissue engineering.

    “However, chitosan is poorly soluble in water under physiological conditions, which limits its widespread use in TE [44].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [44] Wu, 2014, Design of chitosan and its water soluble derivatives-based drug carriers with polyelectrolyte complexes, Mar. Drugs source

      Section 2.2 (Solubility; page unavailable) states that chitosan is insoluble at neutral pH and usually requires acidic solvents to prepare a solution. The paper does not say that this limits its widespread use in tissue engineering; its Introduction instead describes potential bioengineering applications. (LLM, conf=0.86)

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

    Premisecitation

    HA is a linear polyanionic polysaccharide that occurs naturally in all living organisms and maintains an appropriate level of tissue hydration.

    “HA is a linear polyanionic polysaccharide, with the structure of glucuronic acid and N-acetylglucosamine repeating units linked via alternating β-1,4 and β-1,3 glycosidic bonds, which occurs naturally in all living organisms and maintains an appropriate level of tissue hydration [57].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [57] Necas, 2008, Hyaluronic acid (hyaluronan): A review, Vet. Med. source

  • May combine two claims.

    Premisecitation

    Fossil-based polymers usually have a controlled structure, no immunological reaction, and a higher degree of processing flexibility.

    “They usually have a controlled structure, no immunological reaction, and a higher degree of processing flexibility. They can also provide better control over the synthesis and design of the polymer itself [11].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [11] Guo, 2014, Synthetic biodegradable functional polymers for tissue engineering: A brief review, Sci. China Chem. source

      Section 2.1 says synthetic polymers usually have controlled structure, greater processing flexibility, and no immunological concerns. It does not identify them specifically as fossil-based polymers, and ‘no immunological concerns’ does not establish that they cause no immunological reaction. The paper also discusses control over polymer properties through synthesis and design, but not as a comparative advantage of fossil-based polymers. (LLM, conf=0.86)

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

    Premisecitation

    Fibrin naturally assembles into gels and thrombus formation in vivo during wound healing and is an important component of the ECM.

    “Fibrin naturally assembles into gels and thrombus formation in vivo during wound healing and is an important component of the ECM in the body [64].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [64] Leng, 2021, Predicting the mechanical properties of biopolymer gels using neural networks trained on discrete fiber network data, Comput. Methods Appl. Mech. Eng. source

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

    Premisecitation

    Many functional groups have recently been introduced into biopolymers to modify their physical and physiological properties, making them multifunctional and smart.

    “In addition, many functional groups have recently been introduced into biopolymers to modify their physical and physiological properties, making them multifunctional and smart [43].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [43] Zou, 2022, Design of biopolymer-based hemostatic material: Starting from molecular structures and forms, Mater. Today Bio source

  • May combine two claims.

    Premisecitation

    HA is one of the main components of the ECM and can be used to crosslink collagen fibrils, as it participates in mineralization.

    “It is one of the main components of the ECM and can be used to crosslink collagen fibrils, as it participates in mineralization [58].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [58] Zhai, 2020, The application of hyaluronic acid in bone regeneration, Int. J. Biol. Macromol. source

      The Introduction identifies HA as an ECM component, and §4.1 describes its influence on mineralization in a collagen/chitosan/HA scaffold. But §4.1 attributes the scaffold’s crosslinking reaction to chitosan, not to HA crosslinking collagen fibrils; the cited paper does not establish that part of the claim. (LLM, conf=0.86)

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

    Premisecitation

    Electrospun fibers have the potential to be used for drug delivery, wound healing, TE, and regenerative medicine.

    “Electrospun fibers have the potential to be used for drug delivery, wound healing, TE, and regenerative medicine [127].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [127] Bhattarai, R., Bachu, R., Boddu, S.H.S., and Bhaduri, S. (2018). Biomedical Applications of Electrospun Nanofibers: Drug and Nanoparticle Delivery. Pharmaceutics, 11. source

  • May combine two claims.

    Premisecitation

    PHBV is degraded in vivo to hydroxybutyric acid, which is easily metabolized by the body.

    “PHBV is degraded in vivo to hydroxybutyric acid, which is easily metabolized by the body [106].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [106] Kaniuk, 2020, Osteoblasts and fibroblasts attachment to poly(3-hydroxybutyric acid-co-3-hydrovaleric acid) (PHBV) film and electrospun scaffolds, Mater. Sci. Eng. C source

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

    Premisecitation

    Depending on the type of microorganism, growing circumstances, and method of polymer extraction, PHAs can differ in molecular weight, structure, and content.

    “Depending on the type of microorganism, growing circumstances, and method of polymer extraction, they can differ in molecular weight, structure, and content [109,110].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [109] Raza, 2018, Polyhydroxyalkanoates: Characteristics, production, recent developments and applications, Int. Biodeterior. Biodegrad. source
    • cites [110] Pospisilova, 2021, Techniques for increasing the thermal stability of poly[(R)-3-hydroxybutyrate] recovered by digestion methods, Polym. Degrad. Stab. source

      Section 3.1 reports that recovery method affects PHB molecular weight: harsh digestion produced lower-molecular-weight polymer than milder digestion or chloroform extraction of the same biomass. The paper does not establish that microorganism type or growing conditions cause differences in molecular weight, structure, or content across PHAs. (LLM, conf=0.88)

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

    Premisecitation

    PLA is made from renewable and non-toxic sources of raw materials.

    “It is made from renewable and non-toxic sources of raw materials [79].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [79] Su, S., Kopitzky, R., Tolga, S., and Kabasci, S. (2019). Polylactide (PLA) and its blends with poly(butylene succinate) (PBS): A brief review. Polymers, 11. source

      The Introduction states that PLA is derived from renewable resources. Section 7 (Application) describes PLA and PBS as having low toxicity, but it does not say their raw-material sources are non-toxic. No page numbers are available in our copy. (LLM, conf=0.86)

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  • May combine two claims.

    Premisecitation

    One extensively studied combination is PLA combined with HAp, which can be processed using low-cost and stable fused deposition modeling (FDM) technology.

    “One extensively studied combination is PLA combined with HAp, which can be processed using low-cost and stable fused deposition modeling (FDM) technology [189].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [189] Zhang, 2021, 3D printed bone tissue regenerative PLA/HA scaffolds with comprehensive performance optimizations, Mater. Des. source

  • May combine two claims.

    Premisereasoning

    For this reason, sex, age, and comorbidities are also taken into consideration, thus allowing personalized TE.

    “For this reason, sex, age, and comorbidities are also taken into consideration, thus allowing personalized TE [202].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [202] Liu, 2018, Effect of age on biomaterial-mediated in situ bone tissue regeneration, Acta Biomater. source

      The Introduction identifies recipient age as a host-specific factor in biomaterial-mediated bone repair, and the Conclusion reports that age significantly affected bone formation in mice. The paper does not establish that sex or comorbidities are taken into consideration, or that considering these factors enables personalized tissue engineering. (LLM, conf=0.87)

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    Premisecitation

    Depending on the ratio of pro- and anti-inflammatory agents, either extensive fibrosis, in the form of a fibrous capsule, or tissue regeneration evolves from this process.

    “Depending on the ratio of pro- and anti-inflammatory agents, either extensive fibrosis, in the form of a fibrous capsule, or tissue regeneration evolves from this process [204].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [204] Chen, 2021, Foreign Body Reaction to Implanted Biomaterials and Its Impact in Nerve Neuroprosthetics, Front. Bioeng. Biotechnol. source

      The Chronic FBR section says that macrophages switch toward an anti-inflammatory phenotype during the chronic response, yet those cells help form the fibrous capsule. The Acute FBR section describes tissue returning to normal when an implant is degraded. The paper does not say that the ratio of pro- to anti-inflammatory agents determines whether fibrosis or tissue regeneration occurs; page numbers were not provided in our copy. (LLM, conf=0.83)

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    Premisecitation

    Immunoengineering aims to develop easily accessible, resorbable, immunomodulatory scaffolds that would enhance the endogenous pro-regenerative environment in affected sites, in situ.

    “It aims to develop easily accessible, resorbable, immunomodulatory scaffolds that would enhance the endogenous pro-regenerative environment in affected sites, in situ [201].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [201] Russo, V., El Khatib, M., Prencipe, G., Cerveró-Varona, A., Citeroni, M.R., Mauro, A., Berardinelli, P., Faydaver, M., Haidar-Montes, A.A., and Turriani, M. (2022). Scaffold-Mediated Immunoengineering as Innovative Strategy for Tendon Regeneration. Cells, 11. source

      Section 4 says immunoengineering aims to develop immunomodulatory scaffolds that promote a favorable host immune response and tissue regeneration. Section 3 discusses scaffold degradation rates, but the copy does not establish that the scaffolds are intended to be easily accessible or resorbable. The claim’s local, pro-regenerative aim is supported; those two design requirements are not. (LLM, conf=0.86)

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

    Premisereasoning

    Scaffolds should modulate and cooperate with the immune system so that all biochemical processes happening in the affected site lead to tissue repair.

    “In addition, scaffolds should modulate and cooperate with the immune system so that all biochemical processes happening in the affected site lead to tissue repair.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [198] Green, 2021, Immunoengineering has arrived, J. Biomed. Mater. Res. A source

      The Introduction says tissue-engineering scaffolds can be designed for a bioactive, healing interaction with the body through careful engineering of the immune system. “Immunoengineering for Regeneration and Discovery” reports that some scaffolds promote tissue repair through immune responses, but also describes a material that produces fibrosis. The source does not support the claim that all biochemical processes at the affected site can be made to lead to repair. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    The research confirmed the biocompatibility of PLA, as well as endotoxin contamination levels, that were below the FDA limit.

    “The research confirmed the biocompatibility of PLA, as well as endotoxin contamination levels, that were below the FDA limit.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [91] Ritz, U., Gerke, R., Götz, H., Stein, S., and Rommens, P.M. (2017). A new bone substitute developed from 3D-prints of polylactide (PLA) loaded with collagen i: An In Vitro study. Int. J. Mol. Sci., 18. source

  • May combine two claims.

    Premisecitation

    Another challenge is their low bioactivity, which can be addressed by incorporating ceramic materials such as hydroxyapatite (HAp), tricalcium phosphate (TCP), or bioactive glasses.

    “Another challenge is their low bioactivity, which can be addressed by incorporating ceramic materials such as hydroxyapatite (HAp), tricalcium phosphate (TCP), or bioactive glasses.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [184] Dhandayuthapani, 2011, Polymeric Scaffolds in Tissue Engineering Application: A Review, Int. J. Polym. Sci. source

      The “Polymers for Scaffolds” section identifies HAP, TCP, and bioactive glasses as bioactive ceramics and describes combining degradable polymers with inorganic bioactive particles. Section 8 reports high bioactivity for a PLGA/HAP composite scaffold. The copy does not establish that the polymers themselves have low bioactivity, so it supports the proposed composite approach but not the stated challenge. (LLM, conf=0.83)

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

    Premisecitation

    Immunoengineering investigates and modulates each component of TE (materials, cells, and regulatory molecules), considering intervention with the host immune system.

    “Immunoengineering investigates and modulates each component of TE (materials, cells, and regulatory molecules), considering intervention with the host immune system [198].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [198] Green, 2021, Immunoengineering has arrived, J. Biomed. Mater. Res. A source

      The Introduction says immunoengineering investigates and modulates the immune system and includes improving interactions between tissue-engineered constructs and the host. “Immunoengineering for Regeneration and Discovery” discusses biomaterials, immune cells, and signaling molecules, but the paper does not establish that immunoengineering investigates and modulates each component of tissue engineering as the claim states. Page numbers are not available in our copy. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Although many scaffolds have been successfully applied in vivo or utilized in clinical medicine to restore damaged tissues, adverse effects such as extensive inflammatory response leading to transplant rejection were often observed.

    “Although many scaffolds have been successfully applied in vivo or utilized in clinical medicine to restore damaged tissues, adverse effects such as extensive inflammatory response leading to transplant rejection were often observed.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [199] Molina, 2021, Design Challenges in Polymeric Scaffolds for Tissue Engineering, Front. Bioeng. Biotechnol. source

      The Introduction says some engineered tissues have been approved for human use, but transplantation can be limited by complications leading to biomaterial rejection. The Immunomodulation section describes inflammatory responses to implanted scaffolds and says immune reactions usually restrict transplant integration. It does not establish that many scaffolds have been successfully used clinically or that extensive inflammation leading to rejection was often observed. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    While PHB and low molecular weight PLA are miscible, PHB and high molecular weight PLA are not.

    “While PHB and low molecular weight PLA are miscible, PHB and high molecular weight PLA are not [168,180].”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [168] D’Anna, A., Arrigo, R., and Frache, A. (2019). PLA/PHB Blends: Biocompatibilizer Effects. Polymers, 11. source

      The Introduction and Results and Discussion (§3.4; page unavailable) describe PLA/PHB blends as immiscible. The paper does not compare low- and high-molecular-weight PLA or establish that PHB is miscible with the former but not the latter. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [180] Menčík, P., Přikryl, R., Krobot, Š., Melčová, V., Kontárová, S., Plavec, R., Bočkaj, J., Horváth, V., and Alexy, P. (2022). Evaluation of the Properties of PHB Composite Filled with Kaolin Particles for 3D Printing Applications Using the Design of Experiment. Int. J. Mol. Sci., 23. source

      The Introduction states that PHB is miscible with polylactic acid at different ratios and temperatures. It does not distinguish low- from high-molecular-weight PLA or support the claim that PHB and high-molecular-weight PLA are not miscible (searched: low and high molecular weight, miscibility). (LLM, conf=0.86)

      Experimental — accuracy not yet measured

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    Premisecitation

    This stage is also characterized by the recruitment of neutrophils and by the release of the cytokines IL-4 and IL-13 from the mast cells.

    “This stage is also characterized by the recruitment of neutrophils and by the release of the cytokines IL-4 and IL-13 from the mast cells.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [205] Veiseh, 2019, Domesticating the foreign body response: Recent advances and applications, Adv. Drug Deliv. Rev. source

      The Review of the Foreign Body Response section (page not available) says neutrophils appear at the implantation site within hours and predominate for the first two days, supporting their recruitment during the early response. The passages found do not say that mast cells release IL-4 or IL-13, so that part of the claim is unsupported. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

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    Premisecitation

    Adjacent capillaries dilate, and cytokines together with damage-associated molecular patterns (DAMPs) are released from platelets, damaged cells, and ECM.

    “Adjacent capillaries dilate, and cytokines together with damage-associated molecular patterns (DAMPs) are released from platelets, damaged cells, and ECM.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [205] Veiseh, 2019, Domesticating the foreign body response: Recent advances and applications, Adv. Drug Deliv. Rev. source

      The Review of the Foreign Body Response (FBR) says that endogenous structures are released from damaged tissue and that infiltrating monocytes secrete cytokines. It does not describe adjacent capillaries dilating or establish that platelets, damaged cells, and ECM release the stated combination of cytokines and DAMPs. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

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    Premisecitation

    The chronic stage is predominantly mediated by macrophages and foreign body giant cells, which are generated from the fused macrophages.

    “This stage is predominantly mediated by macrophages and foreign body giant cells, which are generated from the fused macrophages.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [207] Barone, 2022, Prevention of the foreign body response to implantable medical devices by inflammasome inhibition, Proc. Natl. Acad. Sci. USA source

      The Discussion names macrophages and foreign body giant cells among cells recruited during the foreign body response, and says macrophages activate fibroblasts that mediate fibrosis. It does not say that macrophages and giant cells predominantly mediate the chronic stage or that giant cells form by macrophage fusion. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

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    Premisenone given

    Lymphocytes also participate, but their role still remains poorly understood.

    “In addition, lymphocytes also participate, but their role still remains poorly understood.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [207] Barone, 2022, Prevention of the foreign body response to implantable medical devices by inflammasome inhibition, Proc. Natl. Acad. Sci. USA source

      The Discussion says the role of dendritic cells in the foreign body response remains poorly understood, but does not make that statement about lymphocytes. The Methods list B cells, T cells and natural killer cells among cell types distinguishable by the RNA-seq analysis; they do not establish the claimed participation or characterize their role. Searches for lymphocytes and their role found no passage that settles the claim. (LLM, conf=0.72)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Scaffold modification with nanohybrid components positively influenced M2 macrophage polarization, osteogenesis, and angiogenesis.

    “Moreover, scaffold modification with nanohybrid components positively influenced the M2 type of macrophage polarization as well as osteogenesis and angiogenesis.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [228] Xue, 2022, Enhanced tissue regeneration through immunomodulation of angiogenesis and osteogenesis with a multifaceted nanohybrid modified bioactive scaffold, Bioact. Mater. source

  • The quote only partly states this claim.

    Premisecitation

    PLA/hydroxyapatite composite scaffolds with nanohybrid surface modification accelerated bone healing in rats with large bone defects.

    “When applied in vivo to repair large bone defects (animal model, rats), accelerated bone healing was observed.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [228] Xue, 2022, Enhanced tissue regeneration through immunomodulation of angiogenesis and osteogenesis with a multifaceted nanohybrid modified bioactive scaffold, Bioact. Mater. source

  • May combine two claims.

    Premisecitation

    Proteins from blood and serum are adsorbed on the scaffold surface, activating the coagulation pathway and leading to the formation of a temporary matrix.

    “Simultaneously, proteins from blood and serum are adsorbed on the scaffold surface, activating the coagulation pathway and leading to the formation of a temporary matrix [205].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [205] Veiseh, 2019, Domesticating the foreign body response: Recent advances and applications, Adv. Drug Deliv. Rev. source

      The Review of the Foreign Body Response section (page unavailable) describes early protein adsorption on implanted biomaterial surfaces, including adsorption of the plasma protein fibrinogen. It does not state that this adsorption activates the coagulation pathway or forms a temporary matrix; searches for those terms and “provisional matrix” found no supporting passage. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Macrophages, by crosstalk with the myofibroblasts, regulate the degradation of the implanted material and also coordinate the formation of granulation tissue, which is the precursor for fibrous capsule development.

    “Macrophages, by crosstalk with the myofibroblasts, regulate the degradation of the implanted material and also coordinate the formation of granulation tissue, which is the precursor for fibrous capsule development [207].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [207] Barone, 2022, Prevention of the foreign body response to implantable medical devices by inflammasome inhibition, Proc. Natl. Acad. Sci. USA source

      The Discussion says macrophages activate acta2-expressing fibroblasts that mediate fibrosis. The paper also says macrophages try to degrade implanted material and are thought to coordinate the fibroblast response that forms a capsule. It does not describe macrophages coordinating granulation-tissue formation or identify granulation tissue as a precursor to the capsule. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    PEG exhibits low immunogenicity and nontoxicity.

    “PEG exhibits low immunogenicity and nontoxicity [29].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [29] Zhang, 2022, Polyethylene glycol crosslinked decellularized single liver lobe scaffolds with vascular endothelial growth factor promotes angiogenesis In Vivo, Hepatobiliary Pancreat. Dis. Int. source

  • May combine two claims.

    Premisecitation

    PU exhibits low cytotoxicity, interfacial tension, high thrombo-resistance, oxygen permeability, and suitable mechanical properties for various pharmaceutical and biomedical applications.

    “In addition, PU exhibits low cytotoxicity, interfacial tension, high thrombo-resistance, oxygen permeability, and suitable mechanical properties for various pharmaceutical and biomedical applications, such as wound dressing materials, drug carriers, and antimicrobial filters [40].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [40] Naureen, 2021, Recent advances in tissue engineering scaffolds based on polyurethane and modified polyurethane, Mater. Sci. Eng. C source

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

    Premisecitation

    Scaffolds should exhibit the ability to withstand mechanical stress.

    “Furthermore, scaffolds should exhibit the ability to withstand mechanical stress [7,8].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [7] De Boer, J., Blitterswijk, C.A.V., Uquillas, J.A., and Malik, N. (2023). Tissue Engineering, Academic Press. [3rd ed.].

      Not checked in the free run.

    • cites [8] De Boer, J., Blitterswijk, C.A.V., Uquillas, J.A., and Malik, N. (2023). Tissue Engineering, Academic Press. [3rd ed.].

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    PCL is an extremely tough aliphatic polyester and is widely used in various biomedical applications.

    “PCL is an extremely tough aliphatic polyester and is widely used in various biomedical applications [16].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] Boccaccini, A.R., Ma, P.X., and Liverani, L. (2022). Tissue Engineering Using Ceramics and Polymers, Woodhead Publishing. [3rd ed.]. Woodhead Publishing Series in Biomaterials.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The deposition of minerals is facilitated by the appropriate arrangement of collagen fibrils, which also enhances the bone's mechanical qualities.

    “The deposition of minerals is facilitated by the appropriate arrangement of collagen fibrils, which also enhances the bone’s mechanical qualities [53].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [53] Liu, 2022, Aging exacerbates the morphological and mechanical response of mineralized collagen fibrils in murine cortical bone to disuse, Acta Biomater. source

  • May combine two claims.

    Premisecitation

    Fossil-based polymers are widely used in tissue engineering, and their chemical, physical, mechanical, and morphological properties can be adjusted according to the intended application.

    “FBPs are widely used in TE, and their chemical, physical, mechanical, and morphological properties (e.g., pore size and distribution, surface texture, typology, and crosslinking) can be adjusted according to the intended application (Figure 2) [13].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] Yang, 2021, Synthesis, Properties, and Applications of Bio-Based Cyclic Aliphatic Polyesters, Biomacromolecules source

  • May combine two claims.

    Premisecitation

    Alginate and chitosan have reduced immunogenicity and demonstrated structural stability.

    “Alginate and chitosan have reduced immunogenicity and demonstrated structural stability as well [48].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [48] Venkatesan, 2014, Chitosan-alginate biocomposite containing fucoidan for bone tissue engineering, Mar. Drugs source

      Checked before — its earlier verdict is held back until a new check runs.

  • May combine two claims.

    Premisecitation

    Degradation of PPF occurs by hydrolysis of ester bonds, and the rate depends on the molecular mass of the main chain, used crosslinkers, and crosslink density.

    “Degradation of PPF occurs by hydrolysis of the ester bonds, and the rate of degradation depends on the molecular mass of the main chain, used crosslinkers, and the crosslink density [35].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] Cai, 2019, Poly(propylene fumarate)-based materials: Synthesis, functionalization, properties, device fabrication and biomedical applications, Biomaterials source

  • May combine two claims.

    Premisecitation

    One of the major advantages of fossil-based polymers is their customizable porosity, large-scale production, and long shelf life.

    “One of their major advantages is their customizable porosity, large-scale production, and long shelf life [15].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] Liu, 2020, Current applications of poly(lactic acid) composites in tissue engineering and drug delivery, Compos. B Eng. source

  • May combine two claims.

    Premisecitation

    Experiments showed that the proliferation and survival rates of fibroblasts were sufficient, allowing skin regeneration.

    “In the context of skin TE, studies have demonstrated that a layer-by-layer method is suitable for modeling PCL scaffolds. These provide a suitable matrix for the fabrication of cell-colonized constructs consisting of epidermal and dermal skin layers. Experiments also showed that the proliferation and survival rates of fibroblasts were sufficient, allowing skin regeneration [16].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] Boccaccini, A.R., Ma, P.X., and Liverani, L. (2022). Tissue Engineering Using Ceramics and Polymers, Woodhead Publishing. [3rd ed.]. Woodhead Publishing Series in Biomaterials.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    PCL has low decomposition rates and is highly flammable, non-toxic, and inexpensive.

    “PCL is bioresorbable and has good stiffness, mechanical elasticity, thermal stability, biocompatibility, and rheological and viscoelastic properties. It has low decomposition rates and is highly flammable, non-toxic, and inexpensive [16].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] Boccaccini, A.R., Ma, P.X., and Liverani, L. (2022). Tissue Engineering Using Ceramics and Polymers, Woodhead Publishing. [3rd ed.]. Woodhead Publishing Series in Biomaterials.

      Not checked in the free run.

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

    Premisecitation

    Fossil-based polymers can be classified according to their hydrophilicity, hydrophobicity, and degradability.

    “These polymers can be classified according to their hydrophilicity, hydrophobicity, and degradability [16].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] Boccaccini, A.R., Ma, P.X., and Liverani, L. (2022). Tissue Engineering Using Ceramics and Polymers, Woodhead Publishing. [3rd ed.]. Woodhead Publishing Series in Biomaterials.

      Not checked in the free run.

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

    Premisecitation

    Because of hydrogen bonds, the main chain's helical shape coils around the side chain.

    “Because of hydrogen bonds, the main chain’s helical shape coils around the side chain [67].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [67] Byram, 2020, Biomimetic silk fibroin and xanthan gum blended hydrogels for connective tissue regeneration, Int. J. Biol. Macromol. source

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

    Premisecitation

    Biomaterials are fundamental components in tissue engineering scaffolds and play a critical role.

    “Biomaterials represent the basic components and play a crucial role in scaffold engineering [2].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] Kalsi, 2021, Biomaterials for tissue engineered bone Scaffolds: A review, Mater. Today Proc. source

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

    Premisecitation

    Biocompatibility is an essential prerequisite for biomaterials, encompassing specific mechanical, biochemical, and physical properties.

    “Biocompatibility is an essential prerequisite for biomaterials, encompassing specific mechanical, biochemical, and physical properties [3].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [3] Schatkoski, 2021, Current advances concerning the most cited metal ions doped bioceramics and silicate-based bioactive glasses for bone tissue engineering, Ceram. Int. source

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

    Premisecitation

    XG side chains are made up of D-mannose and D-glucuronic acid in a 2:1 ratio, and its backbone is the same as that of cellulose.

    “Its side chains are made up of D-mannose and D-glucuronic acid in a 2:1 ratio, and its backbone is the same as that of cellulose [66].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [66] Douglas, 2018, Novel self-gelling injectable hydrogel/alpha-tricalcium phosphate composites for bone regeneration: Physiochemical and microcomputer tomographical characterization, J. Biomed. Mater. Res. A source

      Checked before — its earlier verdict is held back until a new check runs.

  • May combine two claims.

    Premisecitation

    Poor cell adhesion and slow degradability are disadvantages of PCL.

    “On the other hand, poor cell adhesion and slow degradability are disadvantages of this synthetic biopolymer [17].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17] Ilha, 2022, Nanosilica: Polycaprolactone ratio and heat treatment modify the wettability of nanosilica/polycaprolactone coatings for application in aqueous systems, Surf. Interfaces source

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

    Premisecitation

    Standard use of collagen graft substitutes involves seeding them with mesenchymal stem cells, which have the capacity for osteogenic differentiation.

    “Standard use of collagen graft substitutes involves seeding them with mesenchymal stem cells, which have the capacity for osteogenic differentiation [55].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [55] Gharati, 2022, Comparison Capacity of Collagen Hydrogel and Collagen/Strontium Bioglass Nanocomposite Scaffolds with and Without mesenchymal Stem Cells in Regeneration of Critical Sized Bone Defect in a Rabbit Animal Model, Biol. Trace Elem. Res. source

  • May combine two claims.

    Premisecitation

    Composite scaffolds based on collagen and HA enhanced the biological properties of seeded cells, resulting in a higher proliferation and differentiation rate, leading to bone regeneration.

    “Another study determined that composite scaffolds based on collagen and HA enhanced the biological properties of seeded cells, which resulted in a higher proliferation and differentiation rate, leading to bone regeneration [63].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [63] Dawson, 2008, Development of specific collagen scaffolds to support the osteogenic and chondrogenic differentiation of human bone marrow stromal cells, Biomaterials source

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

    Premisecitation

    In fibrin scaffolds, pores are distributed in the range of 0-35.86 μm and 35.86-89.65 μm, with a total porosity of 43.28%.

    “In the fibrin scaffold, pores can be distributed in the range of 0–35.86 µm and 35.86–89.65 µm, with a total porosity of 43.28% [65].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [65] Sawadkar, P., Mandakhbayar, N., Patel, K.D., Buitrago, J.O., Kim, T.H., Rajasekar, P., Lali, F., Kyriakidis, C., Rahmani, B., and Mohanakrishnan, J. (2021). Three dimensional porous scaffolds derived from collagen, elastin and fibrin proteins orchestrate adipose tissue regeneration. J. Tissue Eng., 12. source

      Checked before — its earlier verdict is held back until a new check runs.

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

    Premisecitation

    Recently, nanocomposite fibers using chitosan and XG were created to transmit bioactive compounds.

    “Recently, nanocomposite fibers using chitosan and XG were created to transmit bioactive compounds [68].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [68] Shekarforoush, 2018, Electrospun xanthan gum-chitosan nanofibers as delivery carrier of hydrophobic bioactives, Mater. Lett. source

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

    Premisecitation

    The primary objective of scaffolds is to mimic the structure and function of the extracellular matrix of the original tissue.

    “The primary objective of scaffolds is to mimic the structure and function of the extracellular matrix (ECM) of the original tissue [6].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6] De Boer, J., Blitterswijk, C.A.V., Uquillas, J.A., and Malik, N. (2023). Tissue Engineering, Academic Press. [3rd ed.].

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    High molecular weight HA inhibits cell proliferation and migration, while low molecular weight HA is involved in cell reproduction.

    “High molecular weight HA inhibits cell proliferation and migration, while low molecular weight HA is involved in cell reproduction [60].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [60] Zhao, 2015, Effect of molecular weight and concentration of hyaluronan on cell proliferation and osteogenic differentiation In Vitro, Biochem. Biophys. Res. Commun. source

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

    Premisecitation

    PEG is a water-soluble, non-ionic, and biodegradable synthetic polymer that has a wide range of applications in tissue engineering.

    “PEG is a water-soluble, non-ionic, and biodegradable synthetic polymer that has a wide range of applications in TE [29].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [29] Zhang, 2022, Polyethylene glycol crosslinked decellularized single liver lobe scaffolds with vascular endothelial growth factor promotes angiogenesis In Vivo, Hepatobiliary Pancreat. Dis. Int. source

  • May combine two claims.

    Premisecitation

    PCL is bioresorbable and has good stiffness, mechanical elasticity, thermal stability, biocompatibility, and rheological and viscoelastic properties.

    “PCL is bioresorbable and has good stiffness, mechanical elasticity, thermal stability, biocompatibility, and rheological and viscoelastic properties. It has low decomposition rates and is highly flammable, non-toxic, and inexpensive [16].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] Boccaccini, A.R., Ma, P.X., and Liverani, L. (2022). Tissue Engineering Using Ceramics and Polymers, Woodhead Publishing. [3rd ed.]. Woodhead Publishing Series in Biomaterials.

      Not checked in the free run.

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

    Premisecitation

    PHB is a bioresorbable low-molecular-weight aliphatic polyester and belongs to the most widely used biocompatible PHAs with an isotactic semicrystalline structure.

    “As a bioresorbable low-molecular-weight aliphatic polyester, PHB belongs to the most widely used biocompatible PHAs with an isotactic semicrystalline structure [93].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [93] Bakhtiari, 2021, Modified poly(3-hydroxybutyrate)-based scaffolds in tissue engineering applications: A review, Int. J. Biol. Macromol. source

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

    Premisecitation

    With varying distributions of the isomers in the structure, PLA can be produced in a variety of molecular weights between several thousand and several million.

    “With varying distributions of the isomers in the structure, PLA can be produced in a variety of molecular weights between several thousand and several million [81].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [81] Maadani, 2022, Performance comparison of PLA- and PLGA-coated porous bioceramic scaffolds: Mechanical, biodegradability, bioactivity, delivery and biocompatibility assessments, J. Control. Release source

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

    Premisecitation

    Starch consists of many glucose units connected by glycosidic bonds.

    “This carbohydrate consists of many glucose units connected by glycosidic bonds [73].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [73] Mohamad, 2020, Effect of very fine nanoparticle and temperature on the electric and dielectric properties of MC-PbS polymer nanocomposite films, Results Phys. source

      Checked before — its earlier verdict is held back until a new check runs.

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

    Premisecitation

    Naturally occurring PHAs are ubiquitous components of animal cell membranes.

    “Naturally occurring PHAs are ubiquitous components of animal cell membranes.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [92] Chen, 2013, Elastomeric biomaterials for tissue engineering, Prog. Polym. Sci. source

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

    Premisecitation

    PHB can be produced by many types of microorganisms due to its bacterial origin.

    “In addition, it can be produced by many types of microorganisms due to its bacterial origin [92].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [92] Chen, 2013, Elastomeric biomaterials for tissue engineering, Prog. Polym. Sci. source

  • May combine two claims.

    Premisecitation

    The morphology and crystal structure of PHAs can be modified and influenced by mixing with additives, mainly nucleating agents, suitable plasticizers, and fillers, and are expected to significantly affect physical properties such as thermal, mechanical characteristics, and bioresorbability.

    “The morphology and crystal structure of these materials can be modified and influenced by mixing with additives, mainly nucleating agents, suitable plasticizers, and fillers, and are expected to significantly affect physical properties such as thermal, mechanical characteristics, and bioresorbability [111].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [111] Eesaee, 2022, Morphology and crystallization behaviour of polyhydroxyalkanoates-based blends and composites: A review, Biochem. Eng. J. source

  • May combine two claims.

    Premisecitation

    As the implant bio-resorbs, patients do not need a second surgery to remove it, which lowers healthcare expenses and enables a progressive restoration of tissue function.

    “As the implant bio-resorbs, patients do not need a second surgery to remove it, which lowers healthcare expenses and enables a progressive restoration of tissue function [84].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [84] Singhvi, 2019, Polylactic acid: Synthesis and biomedical applications, J. Appl. Microbiol. source

  • May combine two claims.

    Premisecitation

    By combining several polymers, the costs of the final product can be significantly reduced, and sufficient or even better properties are maintained.

    “By combining, the costs of the final product can be significantly reduced, and sufficient or even better properties are maintained [122].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [122] Visakh, P.M., Markovic, G., and Pasquini, D. (2017). Recent Developments in Polymer Macro, Micro and Nano Blends, Woodhead Publishing.

      Not checked in the free run.

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

    Premisecitation

    Low-molecular-weight poly-3-hydroxybutyrate (P3HB) is present in relatively high concentrations in human blood, and 3-hydroxybutyric acid (3HB) is a naturally occurring human metabolite found in the heart, liver, brain, lungs, and muscle tissue.

    “Low-molecular-weight poly-3-hydroxybutyrate (P3HB) is present in relatively high concentrations in human blood, and 3-hydroxybutyric acid (3HB) is a naturally occurring human metabolite found in the heart, liver, brain, lungs, and muscle tissue [92].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [92] Chen, 2013, Elastomeric biomaterials for tissue engineering, Prog. Polym. Sci. source

  • May combine two claims.

    Premisecitation

    Compared to PCL alone, the PCL/PEG/PCL triblock copolymer has been noted to have lower acidity, higher rate of degradation, as well as lower hydrophilicity, thus making it a better alternative to constructing scaffolds for TE applications.

    “Compared to PCL alone, the PCL/PEG/PCL triblock copolymer has been noted to have lower acidity, higher rate of degradation, as well as lower hydrophilicity, thus making it a better alternative to constructing scaffolds for TE applications [147].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [147] Dolatabadi, 2023, Simvastatin-loaded PCL/PEG nanofibrous scaffold: A prospective approach for suppression 5-fluorouracil resistance in MKN-45 gastric cancer cells, J. Drug Deliv. Sci. Technol. source

  • May combine two claims.

    Premisecitation

    The choice of pore size depends on the method used to construct the scaffold and may have an impact on its mechanical and dynamic stability.

    “The choice of pore size depends on the method used to construct the scaffold and may have an impact on its mechanical and dynamic stability [88].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [88] Baptista, 2021, Morphological and mechanical characterization of 3D printed PLA scaffolds with controlled porosity for trabecular bone tissue replacement, Mater. Sci. Eng. C source

  • May combine two claims.

    Premisecitation

    In tissue engineering, PLA satisfies the requirements to produce scaffold-based implants, since it is a bioabsorbable polymer that is hydrolytically degradable and does not form hazardous compounds while being broken down.

    “In the context of TE, PLA satisfies the requirements to produce scaffold-based implants, since it is a bioabsorbable polymer that is hydrolytically degradable and does not form hazardous compounds while being broken down (Figure 5) [84].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [84] Singhvi, 2019, Polylactic acid: Synthesis and biomedical applications, J. Appl. Microbiol. source

  • May combine two claims.

    Premisecitation

    PHB is a thermoplastic polymer that can easily be processed into textiles with good flexibility.

    “Although PHB is stiff and brittle, with an elongation at break typically less than 5%, its thermoplastic polymer can easily be processed into textiles with good flexibility.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [96] Martin, 2003, Medical applications of poly-4-hydroxybutyrate: A strong flexible absorbable biomaterial, Biochem. Eng. J. source
    • Rests on an assumption: PHB is stiff and brittle, with an elongation at break typically less than 5%.

  • May combine two claims.

    Premisecitation

    PHB is a member of the PHA group and shows a good degree of biocompatibility with various cells.

    “Polyhyroxybutyrate (PHB) is a member of the PHA group and shows a good degree of biocompatibility with various cells.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [92] Chen, 2013, Elastomeric biomaterials for tissue engineering, Prog. Polym. Sci. source

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

    Premisecitation

    PLA has been used in different biomedical applications, as it is fully FDA-approved.

    “PLA has been used in different biomedical applications, as it is fully FDA-approved [82].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [82] Tyler, 2016, Polylactic acid (PLA) controlled delivery carriers for biomedical applications, Adv. Drug Deliv. Rev. source

  • May combine two claims.

    Premisecitation

    Starch hydroxyl groups increase the attraction of phosphate and calcium ions of the bone skeleton, which can speed up apatite nucleation and subsequent bone mineralization, improving overall bone tissue regeneration.

    “Starch hydroxyl groups also increase the attraction of ions (phosphate and calcium) of the bone skeleton, which can speed up and make the apatite nucleation and subsequent bone mineralization faster and more efficient, which improves the overall regeneration of the bone tissue [78].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [78] Mahmoud, 2020, In Vitro and In Vivo study of naturally derived alginate/hydroxyapatite bio composite scaffolds, Int. J. Biol. Macromol. source

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

    Premisecitation

    Various methods exist to chemically crosslink dextran to form a hydrogel.

    “There are various methods to chemically crosslink dextran to form a hydrogel [71].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [71] Batra, 2009, Nonadditive effects of mixed crowding on protein stability, Proteins Struct. Funct. Bioinform. source

      Checked before — its earlier verdict is held back until a new check runs.

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

    Premisecitation

    For the sustained delivery of bioactive compounds, LA and glycolic acid were already proposed as bioresorbable matrices in 1973.

    “For the sustained delivery of bioactive compounds, LA and glycolic acid were already proposed as bioresorbable matrices in 1973 [89].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [89] Auras, 2004, An overview of polylactides as packaging materials, Macromol. Biosci. source

  • May combine two claims.

    Premisecitation

    PCL/PLA has been noted as one of the most investigated blends among biodegradable polymer composites, as they have shown improved mechanical and thermal properties of PCL.

    “PCL/PLA has been noted as one of the most investigated blends among biodegradable polymer composites, as they have shown improved mechanical and thermal properties of PCL.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [123] Ahmed, S. (2021). In Applications of Advanced Green Materials, Woodhead Publishing. Woodhead Publishing in Materials.

      Not checked in the free run.

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

    Premisecitation

    Possible causes of the remaining 10% of the overall porosity are pores larger than 150 μm.

    “Possible causes of the remaining 10% of the overall porosity are pores larger than 150 μm [74].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [74] Karathanos, 1993, Porosity and pore size distribution of starch materials, J. Food Eng. source

  • May combine two claims.

    Premisecitation

    The issue of bulk deterioration and a lack of local flexibility is raised by typically irreversible chemical crosslinking.

    “The issue of bulk deterioration and a lack of local flexibility is raised by typically irreversible chemical crosslinking [117].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [117] Banerjee, 2021, Dextran-based scaffolds for in-situ hydrogelation: Use for next generation of bioartificial cardiac tissues, Carbohydr. Polym. source

  • May combine two claims.

    Premisecitation

    Due to its high crystallinity, PHBV is stiff and brittle, resulting in very poor mechanical properties.

    “Due to its high crystallinity, PHBV is stiff and brittle, resulting in very poor mechanical properties.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [101] Tong, 2012, Electrospinning and Evaluation of PHBV-Based Tissue Engineering Scaffolds with Different Fibre Diameters, Surface Topography and Compositions, J. Biomater. Sci. Polym. Ed. source

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Premisecitation

    Biodegradable matrices recommended for hard tissue tissue engineering must be uniformly degraded in the human body during bone mineralization to improve bone tissue replacement and growth processes.

    “Biodegradable matrices recommended for hard tissue TE must be uniformly degraded in the human body during bone mineralization to improve bone tissue replacement and growth processes [77].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [77] You, 2022, Dielectric and biodegradation properties of biodegradable nano-hydroxyapatite/starch bone scaffold, J. Mater. Res. Technol. source

      Checked before — its earlier verdict is held back until a new check runs.

  • May combine two claims.

    Premisecitation

    The degradation product of PHB is 3HB, which is non-toxic and a natural metabolite occurring in multiple tissues in the human body.

    “The degradation product of PHB is 3HB, which is non-toxic and, as mentioned above, a natural metabolite occurring in multiple tissues in the human body [92].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [92] Chen, 2013, Elastomeric biomaterials for tissue engineering, Prog. Polym. Sci. source

  • May combine two claims.

    Premisecitation

    PCL blends exhibited better mechanical, thermal, or viscoelastic properties.

    “Moreover, PCL blends exhibited better mechanical, thermal, or viscoelastic properties [123].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [123] Ahmed, S. (2021). In Applications of Advanced Green Materials, Woodhead Publishing. Woodhead Publishing in Materials.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The addition of PEG improves the hydrophilicity of PCL, and so cell adherence is also enhanced.

    “The addition of PEG improves the hydrophilicity of PCL, and so cell adherence is also enhanced.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [147] Dolatabadi, 2023, Simvastatin-loaded PCL/PEG nanofibrous scaffold: A prospective approach for suppression 5-fluorouracil resistance in MKN-45 gastric cancer cells, J. Drug Deliv. Sci. Technol. source

  • May combine two claims.

    Premisecitation

    PHBV has a high melting point and high crystallization.

    “PHBV has a high melting point and high crystallization.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [101] Tong, 2012, Electrospinning and Evaluation of PHBV-Based Tissue Engineering Scaffolds with Different Fibre Diameters, Surface Topography and Compositions, J. Biomater. Sci. Polym. Ed. source

  • May combine two claims.

    Premisecitation

    The dominant agent controlling the final mechanical properties of PCL/starch blends is the composite/component ratio, which makes it possible to design a highly stiff (more starch content) or more flexible and thermoplastic (more PCL content) scaffold.

    “The dominant agent controlling the final mechanical properties is the composite/component ratio, which makes it possible to design a highly stiff (more starch content) or more flexible and thermoplastic (more PCL content) scaffold.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [163] Ghavimi, 2014, Polycaprolactone/starch composite: Fabrication, structure, properties, and applications, J. Biomed. Mater. Res. A source

  • May combine two claims.

    Premisecitation

    These ceramics interact with physiological fluids and form strong bonds to hard tissues, and in some cases, soft tissues, through cellular activity.

    “These ceramics interact with physiological fluids and form strong bonds to hard tissues, and in some cases, soft tissues, through cellular activity.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [184] Dhandayuthapani, 2011, Polymeric Scaffolds in Tissue Engineering Application: A Review, Int. J. Polym. Sci. source

      Checked before — its earlier verdict is held back until a new check runs.

  • May combine two claims.

    Premisecitation

    PCL/starch blends present biomaterials with proven biocompatibility and anti-inflammatory characteristics.

    “PCL/starch blends present biomaterials with proven biocompatibility and anti-inflammatory characteristics.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [163] Ghavimi, 2014, Polycaprolactone/starch composite: Fabrication, structure, properties, and applications, J. Biomed. Mater. Res. A source

  • May combine two claims.

    Premisecitation

    Bioceramics possess excellent biocompatibility, osteoinductivity, corrosion resistance, and high compressive strength.

    “They possess excellent biocompatibility, osteoinductivity, corrosion resistance, and high compressive strength.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [185] Thomas, S., Balakrishnan, P., and Sreekala, M.S. (2018). Fundamental Biomaterials: Ceramics, Woodhead Publishing. Woodhead Publishing Series in Biomaterials.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing).

    Premisecitation

    K. J. Zhu alleged that the rates of drug release and biodegradation could be tailored by adjusting polymer composition.

    “K. J. Zhu alleged that the rates of drug release and biodegradation could be tailored by adjusting polymer composition [170].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [170] Zhu, 1990, Preparation, characterization, and properties of polylactide (PLA)–poly(ethylene glycol) (PEG) copolymers: A potential drug carrier, J. Appl. Polym. Sci. source

  • May combine two claims.

    Premisecitation

    PLA has better processability, reproducibility, and mechanical properties, but crystallization, brittleness, low thermal resistance, and low heat deflection temperature are considered to be major disadvantageous properties of PLA.

    “Despite having better processability, reproducibility, and mechanical properties, on the other hand, crystallization, brittleness, low thermal resistance, and low heat deflection temperature are considered to be major disadvantageous properties of PLA.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [167] Rangappa, S.M., Parameswaranpillai, J., Siengchin, S., and Ramesh, M. (2022). Biodegradable Polymers, Blends and Composites, Woodhead Publishing. Woodhead Publishing Series in Composites Science and Engineering.

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    This type of material could be adjusted for 3D printing technology, and thus achieve the engineering of patient-tailored bone grafts.

    “It means that this type of material could be adjusted for 3D printing technology, and thus achieve the engineering of patient-tailored bone grafts [173,174,175].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [173] Salehi, 2022, The effect of polyethylene glycol on printability, physical and mechanical properties and osteogenic potential of 3D-printed poly (l-lactic acid)/polyethylene glycol scaffold for bone tissue engineering, Int. J. Biol. Macromol. source
    • cites [174] Serra, 2014, Relevance of PEG in PLA-based blends for tissue engineering 3D-printed scaffolds, Mater. Sci. Eng. C source
    • cites [175] Asadollahi, 2022, Improving mechanical properties and biocompatibility of 3D printed PLA by the addition of PEG and titanium particles, using a novel incorporation method, Bioprinting source

  • May combine two claims.

    Premisecitation

    Bioceramics have limitations, including a brittle surface, low fracture toughness, reduced mechanical reliability, low elasticity, and exceptionally high stiffness compared to human bone's cortical properties.

    “However, they also have limitations, including a brittle surface, low fracture toughness, reduced mechanical reliability, low elasticity, and exceptionally high stiffness compared to human bone’s cortical properties.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [185] Thomas, S., Balakrishnan, P., and Sreekala, M.S. (2018). Fundamental Biomaterials: Ceramics, Woodhead Publishing. Woodhead Publishing Series in Biomaterials.

      Not checked in the free run.

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

    Premisecitation

    Bioceramics belong to a class of inorganic and nonmetallic ceramics utilized for repairing and reconstructing damaged musculoskeletal and periodontal structures.

    “Bioceramics belong to a class of inorganic and nonmetallic ceramics utilized for repairing and reconstructing damaged musculoskeletal and periodontal structures.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [185] Thomas, S., Balakrishnan, P., and Sreekala, M.S. (2018). Fundamental Biomaterials: Ceramics, Woodhead Publishing. Woodhead Publishing Series in Biomaterials.

      Not checked in the free run.

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

    Premisecitation

    Already in 1990, the PLA/PEG block copolymers were characterized as potential materials suitable for drug carriers.

    “Already in 1990, the PLA/PEG block copolymers were characterized as potential materials suitable for drug carriers.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [170] Zhu, 1990, Preparation, characterization, and properties of polylactide (PLA)–poly(ethylene glycol) (PEG) copolymers: A potential drug carrier, J. Appl. Polym. Sci. source

  • May combine two claims.

    Premisecitation

    The authors focused on the characterization of the 3D printed PLA/PHB-derived objects, and results showed their favorable mechanical properties, thermal stabilities, and cell viability.

    “The authors focused on the characterization of the 3D printed PLA/PHB-derived objects, and results showed their favorable mechanical properties, thermal stabilities, and cell viability [182].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [182] Rydz, 2018, A comparative study of three-dimensional printing directions: The degradation and toxicological profile of a PLA/PHA blend, Polym. Degrad. Stab. source

  • May combine two claims.

    Premisecitation

    Bioceramics exhibit higher strength under compression but are weaker under tension, necessitating careful consideration when designing scaffolds for specific biomedical applications.

    “Bioceramics exhibit higher strength under compression but are weaker under tension, necessitating careful consideration when designing scaffolds for specific biomedical applications [185].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [185] Thomas, S., Balakrishnan, P., and Sreekala, M.S. (2018). Fundamental Biomaterials: Ceramics, Woodhead Publishing. Woodhead Publishing Series in Biomaterials.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    Although PLA/PHB blends hold great potential to be applied in the form of scaffolds to repair damaged tissues, more research is needed in this field to adjust the blend's properties so scaffolds with advanced characteristics can be engineered.

    “Although PLA/PHB blends hold great potential to be applied in the form of scaffolds to repair damaged tissues, more research is needed in this field to adjust the blend’s properties so scaffolds with advanced characteristics can be engineered.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The porous structure of PCL/PLA scaffolds for TE is favorable and almost necessary.

  • May combine two claims.

    Premisecitation

    The addition of PLA to HAp significantly alters the mechanical properties from brittle to ductile fracture, leading to notable improvements in flexural and compressive strength.

    “The addition of PLA to HAp significantly alters the mechanical properties from brittle to ductile fracture, leading to notable improvements in flexural and compressive strength [194].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [194] Hu, 2023, Cold sintering constructed in situ drug-loaded high strength HA-PLA composites: Potential bone substitution material, Ceram. Int. source

  • May combine two claims.

    Interpretationreasoning

    Through controlled porous structures and scaffold design, the material can further regulate degradation and facilitate new bone formation according to the patient's requirements.

    “Through controlled porous structures and scaffold design, the material can further regulate degradation and facilitate new bone formation according to the patient’s requirements.”
    Quote in the paperNot a substantial claim

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

    Interpretationnone given

    Fabricating an ideal scaffold that fulfills all desired properties remains a challenge.

    “However, fabricating an ideal scaffold that fulfills all desired properties, including biocompatibility, biodegradability, viscoelasticity, mechanical strength, structural stability, antimicrobial activity, clinical simplicity, and cost-effectiveness, remains a challenge.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    The solution might present the incorporation of basic molecules with the ability to neutralize redundant acidity and maintain pH homeostasis in this biochemical environment.

    “The solution might present the incorporation of basic molecules with the ability to neutralize redundant acidity and maintain pH homeostasis in this biochemical environment [219].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [219] Shen, 2019, Electrospun acid-neutralizing fibers for the amelioration of inflammatory response, Acta Biomater. source

  • May combine two claims.

    Premisecitation

    Non-degradable materials usually provoke the formation of the fibrotic capsule, which in some cases might be beneficial (artificial joint stabilization).

    “Non-degradable materials usually provoke the formation of the fibrotic capsule, which in some cases might be beneficial (artificial joint stabilization).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [208] Ye, 2021, Promoting musculoskeletal system soft tissue regeneration by biomaterial-mediated modulation of macrophage polarization, Bioact. Mater. source

      Checked before — its earlier verdict is held back until a new check runs.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationnone given

    Development of 3D scaffolds holds promise for improved tissue regeneration, transitioning from animal studies to intended clinical use.

    “Despite significant progress in biomaterial research, the development of 3D scaffolds holds promise for improved tissue regeneration, transitioning from animal studies to intended clinical use.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Results from animal studies of 3D scaffolds translate to intended clinical use in humans.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Premisecitation

    Scaffold-based in situ tissue engineering presents a new perspective for the effective restoration of damaged organs.

    “In the context of regenerative medicine, scaffold-based in situ TE presents a new perspective for the effective restoration of damaged organs [229].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [229] Cao, 2020, New perspectives: In-situ tissue engineering for bone repair scaffold, Compos. B Eng. source

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Interpretationreasoning

    Considering all the aforementioned facts, hybrid bio-based/fossil-based scaffolds might present a good compromise for scaffold immunoengineering.

    “Considering all the aforementioned facts, hybrid bio-based/fossil-based scaffolds might present a good compromise for scaffold immunoengineering.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    The acute inflammatory phase lasts approximately 3-7 days.

    “The acute inflammatory phase lasts approximately 3–7 days.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [203] Chandorkar, 2019, The Foreign Body Response Demystified, ACS Biomater. Sci. Eng. source

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

    Interpretationreasoning

    Combining multiple biomaterials to create hybrid materials with enhanced functionalities has the potential to overcome the limitations of each material and meet clinical requirements.

    “The combination of multiple biomaterials to create hybrid materials with enhanced functionalities has the potential to overcome the limitations of each material and meet clinical requirements.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationnone given

    Biomaterials discussed in this review offer advantages as scaffold materials in tissue engineering but also have limitations that restrict their individual applications.

    “While the biomaterials discussed in this review offer advantages as scaffold materials in TE, they also have limitations that restrict their individual applications.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    It is also crucial to control degradation kinetics, mechanical stimuli, and oxygen concentrations in the transplanted site.

    “It is also crucial to control degradation kinetics, mechanical stimuli, and oxygen concentrations in the transplanted site [210].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [210] Zhang, 2021, Effect of cyclic mechanical loading on immunoinflammatory microenvironment in biofabricating hydroxyapatite scaffold for bone regeneration, Bioact. Mater. source

      Checked before — its earlier verdict is held back until a new check runs.

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

    Interpretationnone given

    Geometrical features such as exposed surface area, pore distribution, porosity, and architecture influence the rate of cell penetration within the scaffold volume and the formation of extracellular matrix.

    “Geometrical features such as exposed surface area, pore distribution, porosity, and architecture influence the rate of cell penetration within the scaffold volume and the formation of the extracellular matrix (ECM).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Conversely, they ought to modulate immune cells together with the degree of inflammation and thus hinder fibrosis of the tissue.

    “Conversely, they ought to modulate immune cells together with the degree of inflammation and thus hinder fibrosis of the tissue [209].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [209] Tan, 2021, Decellularized scaffold and its elicited immune response towards the host: The underlying mechanism and means of immunomodulatory modification, Biomater. Sci. source

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

    Premisecitation

    Immunomodulatory scaffolds should have properties that will not negatively interfere with the host immune system and cause extensive scar formation.

    “Immunomodulatory scaffolds should have properties that will not negatively interfere with the host immune system and cause extensive scar formation.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [209] Tan, 2021, Decellularized scaffold and its elicited immune response towards the host: The underlying mechanism and means of immunomodulatory modification, Biomater. Sci. source

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

    Interpretationreasoning

    However, multiple big pores might negatively affect the mechanical stability of the structure, so an adequate balance needs to be found.

    “However, multiple big pores might negatively affect the mechanical stability of the structure, so an adequate balance needs to be found.”
    Quote in the paperNot a substantial claim

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

    Premisenone given

    In situ tissue engineering technology relies on advanced, bioactive, cell-free scaffolds, which should trigger endogenous healing mechanisms at the affected site.

    “On the contrary, in situ TE technology relies on the application of advanced, bioactive, cell-free scaffolds, which should trigger the endogenous healing mechanisms right at the affected site.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationnone given

    Many of the reviewed materials have not been fully optimized for particular tissue engineering applications.

    “However, it should be noted that many of these materials have not been fully optimized for particular TE applications, and further work is needed to optimize their formulations for translation into clinical practice for targeted applications.”
    Quote in the paperSubstantial claim
114 of 114

  • The paper relies on this without support.

    Increasing demand for organs and tissues, driven by limitations of autografts and allografts, has stimulated the development of tissue engineering.

    “Increasing demand for organs and tissues, driven by the need to address limitations associated with autografts and allografts, has stimulated the development of TE as a field of scientific inquiry.”

  • The paper relies on this without support.

    Bio-based polymer scaffolds generally exhibit minimal immune responses and promote favorable cell interactions.

    “Bio-based polymer scaffolds generally exhibit minimal immune responses and promote favorable cell interactions, while fossil-based polymers are comparatively more economical, possess greater strength and offer improved functionality.”

  • The paper relies on this without support.

    Fossil-based polymers may exert toxic effects and elicit adverse immune responses.

    “However, they may exert toxic effects and elicit adverse immune responses.”

  • The paper relies on this without support.

    Hybrid biomaterials exhibit enhanced functionalities and can address limitations associated with individual materials.

    “Hybrid biomaterials, comprising combinations of two or more biomaterials, exhibit enhanced functionalities and can address the limitations associated with individual materials, thereby satisfying a broad range of clinical requirements.”

  • The paper relies on this without support.

    The interaction between biomaterial-based scaffolds and the host organism is crucial for their successful translation into clinical medicine.

    “Notably, the interaction between biomaterial-based scaffolds and the host organism is described, as this phenomenon is deemed crucial for their successful translation into clinical medicine.”

  • The paper relies on this without support.

    Current trends in scaffold fabrication are more focused on natural or bio-based polymers.

    “However, current trends in scaffold fabrication are more focused on natural or bio-based polymers.”

  • The paper relies on this without support.

    PHB is stiff and brittle, with an elongation at break typically less than 5%.

    “Although PHB is stiff and brittle, with an elongation at break typically less than 5%, its thermoplastic polymer can easily be processed into textiles with good flexibility.”

  • The paper relies on this without support.

    Numerous factors of chemical synthesis, including bulk material processing, surface treatment, sterilization, and adding a plasticizer to the polymer matrix, have a significant impact on the biocompatibility of the final medical implant.

    “Additionally, numerous other factors of chemical synthesis, including bulk material processing, surface treatment, sterilization, and adding a plasticizer to the polymer matrix, have a significant impact on the biocompatibility of the final medical implant.”

  • The paper relies on this without support.

    The biocompatibility, bioresorbability, and wet electrospinnability have allowed PHBV to be widely accepted as a microbial copolymer that is often used for TE of scaffolds.

    “The biocompatibility, bioresorbability, and wet electrospinnability have allowed PHBV to be widely accepted as a microbial copolymer that is often used for TE of scaffolds.”

  • The paper relies on this without support.

    The advantage of PHBV is that it minimizes the risk of inflammatory reactions in tissues since its biodegradation products are components of human blood.

    “The advantage of PHBV is that it minimizes the risk of inflammatory reactions in tissues since its biodegradation products are components of human blood.”

  • The paper relies on this without support.

    The porous structure of PCL/PLA scaffolds for TE is favorable and almost necessary.

    “The porous structure of PCL/PLA scaffolds for TE is favorable and almost necessary.”

  • The paper relies on this without support.

    Scaffolds derived from PLA/PHB blends do not have the porous structure necessary for TE.

    “However, scaffolds derived from PLA/PHB blends do not have the porous structure necessary for TE.”

  • The paper relies on this without support.

    The degradation of natural polymer matrices cannot be precisely controlled, which leads to a discrepancy between scaffold degradation and the formation of the new tissue.

    “On the other hand, the degradation of these matrices cannot be precisely controlled, which leads to a discrepancy between scaffold degradation and the formation of the new tissue.”

  • The authors state this as an assumption.

    Scaffold-driven immune response affects the recruitment of endogenous stem cells and regulatory molecules responsible for the healing process.

    “It is assumed that scaffold-driven immune response further affects the recruitment of endogenous stem cells and regulatory molecules responsible for the healing process [232].”

  • The paper relies on this without support.

    Type-2 immune response constitutes protective immunity.

    “These findings indicated that biological scaffolds induced type-2 immune response (i.e., protective immunity).”

  • The paper relies on this without support.

    Results from animal studies of 3D scaffolds translate to intended clinical use in humans.

    “Despite significant progress in biomaterial research, the development of 3D scaffolds holds promise for improved tissue regeneration, transitioning from animal studies to intended clinical use.”
16 of 16

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.

  • The listed fibrillar collagen types total eight, not seven

    Minor

    Types I-V account for five types; adding XI, XXIV, and XXVII gives eight, contrary to the stated seven.

  • PEG addition is said to both increase and decrease PCL hydrophilicity

    Minor

    The paragraph says adding PEG improves PCL hydrophilicity, then says a PCL/PEG/PCL copolymer has lower hydrophilicity than PCL alone.

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 8

  1. De Boer, J., Blitterswijk, C.A.V., Uquillas, J.A., and Malik, N. (2023). Tissue Engineering, Academic Press. [3rd ed.].
  2. De Boer, J., Blitterswijk, C.A.V., Uquillas, J.A., and Malik, N. (2023). Tissue Engineering, Academic Press. [3rd ed.].
  3. De Boer, J., Blitterswijk, C.A.V., Uquillas, J.A., and Malik, N. (2023). Tissue Engineering, Academic Press. [3rd ed.].
  4. Affar, 2018, Poly(ethylene glycol) (PEG) and Synthetic PEG Derivatives for Tissue Engineering and Cell Delivery, Mater. Matters, 13, 90
  5. Song, W., Lee, B.H., Li, H., and Tan, L.P. (2019). Biomaterials in Translational Medicine, Academic Press.
  6. Ragunathan, S., Govindasamy, G., Raghul, D.R., Karuppaswamy, M., and VijayachandraTogo, R.K. (2019). Materials Today: Proceedings, Elsevier Ltd.
  7. Sandanamsamy, L., Harun, W.S.W., Ishak, I., Romlay, F.R.M., Kadirgama, K., Ramasamy, D., Idris, S.R.A., and Tsumori, F. (2022). Progress in Additive Manufacturing, Springer Science and Business Media Deutschland GmbH.
  8. Freier, T. (2006). Polymers for Regenerative Medicine, Springer.

Cited by

Sorted by citations

Related

Authors
Vach Agocsova, S., Culenova, M., Birova, I., Omanikova, L., Moncmanova, B., Danisovic, L., Ziaran, S., Bakos, D., & Alexy, P.
Affiliations
  • Institute of Natural and Synthetic Polymers, Faculty of Chemical and Food Technology, Slovak University of Technology, 812 37 Bratislava, Slovakia
  • Panara a.s., Krskanska 21, 949 05 Nitra, Slovakia
  • Slovak University of Technology in Bratislava (SK)
  • National Institute of Rheumatic Diseases, Nabrezie I. Krasku 4, 921 12 Piestany, Slovakia
Corresponding author
Culenova, Martina
ORCID
Venue
Materials
Publisher
MDPI AG
Published
2023-06-08
Volume
16
Issue
12
Pages
4267
ISSN
1996-1944 (ISSN-L)
DOI
10.3390/ma16124267
PMC
PMC10301242
OpenAlex
W4380085278
Cited by
98
References
217
Citations by year
2026: 28 · 2025: 42 · 2024: 25 · 2023: 3
FWCI
2.13
Type
journal article
Language
en
Open access
Licence
Locations
  • Materials (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • CEMBAM—Center for Medical Bioadditive Research and Production, ITMS2014+ (313011V358)
  • Operational Programme Integrated Infrastructure (313011V358)
  • European Regional Development Fund (313011V358)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
  • Physical Sciences › Materials Science › Biomaterials › biodegradable polymer synthesis and properties
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
Keywords
resorbable biomaterials, 3D scaffolds, tissue engineering, biodegradable polymers, hybrid biomaterials, biocompatibility, biodegradability, host immune response, tissue regeneration, in situ tissue engineering, biopolymer scaffolds, hard tissue engineering, soft tissue engineering, chitosan, collagen, hydrogels, polycaprolactone, polylactic acid

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 2026-11-05.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-11-05.

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.

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

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