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Cited by 103Bone Tissue Engineering Materialsbiodegradable polymer synthesis and propertiesNonlinear Optical Materials Studies

In vitro degradation and mechanical properties of PLA-PCL copolymer unit cell scaffolds generated by two-photon polymerization

Open access
Felfel, R M, Poocza, Leander, Gimeno-Fabra, Miquel, Milde, Tobias, Hildebrand, Gerhard, Ahmed, Ifty, Scotchford, Colin, Sottile, Virginie +2 more·2016·Biomedical Materials
DOI 10.1088/1748-6041/11/1/015011
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Abstract

The manufacture of 3D scaffolds with specific controlled porous architecture, defined microstructure and an adjustable degradation profile was achieved using two-photon polymerization (TPP) with a size of 2 × 4 × 2 mm(3). Scaffolds made from poly(D,L-lactide-co-ɛ-caprolactone) copolymer with varying lactic acid (LA) and ɛ -caprolactone (CL) ratios (LC16:4, 18:2 and 9:1) were generated via ring-opening-polymerization and photoactivation. The reactivity was quantified using photo-DSC, yielding a double bond conversion ranging from 70% to 90%. The pore sizes for all LC scaffolds were see 300 μm and throat sizes varied from 152 to 177 μm. In vitro degradation was conducted at different temperatures; 37, 50 and 65 °C. Change in compressive properties immersed at 37 °C over time was also measured. Variations in thermal, degradation and mechanical properties of the LC scaffolds were related to the LA/CL ratio. Scaffold LC16:4 showed significantly lower glass transition temperature (T g) (4.8 °C) in comparison with the LC 18:2 and 9:1 (see 32 °C). Rates of mass loss for the LC16:4 scaffolds at all temperatures were significantly lower than that for LC18:2 and 9:1. The degradation activation energies for scaffold materials ranged from 82.7 to 94.9 kJ mol(-1). A prediction for degradation time was applied through a correlation between long-term degradation studies at 37 °C and short-term studies at elevated temperatures (50 and 65 °C) using the half-life of mass loss (Time (M1/2)) parameter. However, the initial compressive moduli for LC18:2 and 9:1 scaffolds were 7 to 14 times higher than LC16:4 (see 0.27) which was suggested to be due to its higher CL content (20%). All scaffolds showed a gradual loss in their compressive strength and modulus over time as a result of progressive mass loss over time. The manufacturing process utilized and the scaffolds produced have potential for use in tissue engineering and regenerative medicine applications.

Integrity signals

Registry

Crossref · 10.1088/1748-6041/11/1/015011

Cites

78 of 78 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

7 of 58 cited sources checked · 2 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    The molecular weight of LA is higher than CL (114.14 and 144.13 g mol -1 for CL and LA respectively).

    “This was attributed to the fact that the molecular weight of LA was higher than CL (114.14 and 144.13 g mol -1 for CL and LA respectively [52,53]).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [52] Li, 2013, Synthesis, characterization and reactivity of single-site aluminium amides bearing benzotriazole phenoxide ligands: catalysis for ring-opening polymerization of lactide and carbon dioxide/propylene oxide coupling, Dalton Trans. source
    • cites [53] Heijkants, 2005, Extruder synthesis of a new class of polyurethanes: Polyacylurethanes based on poly(ε-caprolactone) oligomers, Polymer source

      Section 3.4, Thermal properties (page unavailable), gives 114.14 g/mol as the molecular mass of an ε-caprolactone monomer. The paper does not give 144.13 g/mol for LA or compare LA’s molecular weight with CL’s, so it supports only the CL value. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
  • Interpretationcitation

    The limited variation in pore sizes between different LC scaffolds meant these small differences would not influence the degradation effect observed.

    “However the limited variation in the pore sizes between different LC scaffolds [69,70] meant these small differences would not influence the degradation effect observed.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [69] Sung, 2004, The effect of scaffold degradation rate on 3D cell growth and angiogenesis, Biomaterials source
    • cites [70] Yang, 2001, The design of scaffolds for use in tissue engineering. Part I. Traditional factors, Tissue Eng. source

      The indexed passages on pore sizes (FIG. 3, page unavailable) and degradation (Materials, page unavailable) discuss separate topics. A search for pore-size effects on degradation found no passage addressing LC scaffolds or showing that small pore-size differences would not influence the observed degradation effect. (LLM, conf=0.72)

      Experimental — accuracy not yet measured
    • Rests on an assumption: The surface area/volume ratio of the scaffolds depends on pore size, and the degradation rate of scaffolds is expected to increase as the surface area/volume ratio increases.
  • Findingown data

    The translation of the STL model to the structure was good and reproducible in terms of pores and throat sizes achieved.

    “The translation of the STL model to the structure (see figure 5) was good and reproducible in terms of pores and throat sizes achieved (see table 3).”
    Quote in the paperNot a substantial claim
  • Findingown data

    When rating the different compositions in terms of conversion percentage at 30 °C, they followed the order of LC16:4 > 18:2 > 9:1.

    “When rating the different compositions in terms of conversion percentage at 30 °C, they followed the order of LC16:4 > 18:2 > 9:1.”
    Quote in the paperNot a substantial claim
  • Findingreasoning

    Pore geometry deviated from spherical shape to ellipsoidal with aspect ratio of approximately 1.10 for the produced scaffolds.

    “Pore geometry deviated from spherical shape to ellipsoidal with aspect ratio of approximately 1.10 for the produced scaffolds.”
    Quote in the paperNot a substantial claim
  • May combine two claims. 32
  • Classified as probably not a substantial claim. 27

  • May combine two claims.

    Premisecitation

    Recent approaches managed to create scaffolds bigger than 15 mm3 and offer encouraging preclinical results, underlining the potential of TPP to deliver microstructures of good reproducibility at scale.

    “Nevertheless the technology is constantly improving and recent approaches managed to create scaffolds bigger than 15 mm 3 [74,75] and offer encouraging preclinical results [76] underlining the potential of TPP to deliver microstructures of good reproducibility at scale.”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [74] Hsieh, 2010, 3D microstructured tissue scaffolds fabricated by two-photon laser scanning photolithography, Biomaterials source
    • cites [75] Ovsianikov, 2012, Engineering 3D cell-culture matrices: multiphoton processing technologies for biological and tissue engineering applications, Expert Rev. Med. Devices source
    • cites [76] Bückmann, 2014, An elasto-mechanical unfeelability cloak made of pentamode metamaterials, Nat. Commun. source

      The cited paper’s Numerical calculations section describes a fabricated pentamode cloak microstructure with a total volume of 2 mm³, not a scaffold larger than 15 mm³. The preclinical-results phrase has a separate citation [76] and is not attributed to this source. (LLM, conf=0.88)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured

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

    Premisecitation

    Several research groups have investigated the potential of 2PP for biomedical applications with biocompatible resins such as PLA, PCL, PEG or the use of proteins as scaffold material, which have the potential for clinical application.

    “Several research groups have been investigated the potential of 2PP for biomedical applications with biocompatible resins such as PLA [28], PCL [29], PEG [30] or the use of proteins as scaffold material [31,32], which have the potential for clinical application [33].”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [28] Danilevicius, 2015, The effect of porosity on cell ingrowth into accurately defined, laser-made, polylactide-based 3D scaffolds, Appl. Surf. Sci. source
    • cites [29] Claeyssens, 2009, 3D Biodegradable Structures Fabricated by Two-Photon Polymerization, Langmuir source
    • cites [30] Ovsianikov, 2011, 3D laser micro- and nano-structuring of acrylated poly(ethylene glycol) materials and evaluation of their cytoxicity for tissue engineering applications, Acta Biomater. source

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

    Premisecitation

    Gamma radiation was preferred as a method of sterilisation due to its high efficiency, high penetration and negligible thermal effects.

    “Gamma radiation was preferred as a method of sterilisation due to its high efficiency, high penetration and negligible thermal effects [61].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [61] Cottam, 2009, Effect of sterilisation by gamma irradiation on the ability of polycaprolactone (PCL) to act as a scaffold material, Med. Eng. Phys. source

      The Introduction says gamma irradiation is likely to be the method of choice for many PCL implants and is highly penetrative. Section 2.2 describes the dose used to ensure thorough sterilisation, but the paper does not give high efficiency or negligible thermal effects as reasons for preferring it. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

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

    Premisecitation

    Resolutions of up to 50 μm have been achieved using photo-polymerization techniques for the spatial patterning of materials in a layer-by-layer approach by stereo-lithography.

    “Resolutions of up to 50 μm have been achieved using photo-polymerization techniques for the spatial In vitro degradation and mechanical properties of PLA-PCL copolymer unit cell scaffolds generated by two-photon polymerization patterning of materials in a layer-by-layer approach by stereo-lithography [16,17].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [16] Stampfl, 2008, Photopolymers with tunable mechanical properties processed by laser-based high-resolution stereolithography, J. Micromech. Microeng. source
    • cites [17] Lee, 2007, Poly(propylene fumarate) bone tissue engineering scaffold fabrication using stereolithography: effects of resin formulations and laser parameters, Biomacromolecules source

  • May combine two claims.

    Premisecitation

    The required time for complete resorption of PDLLA is approximately 1-2 years, whilst PCL requires 2-4 years.

    “It was reported that the required time for complete resorption (degradation time) of poly(D,L-lactide) (PDLLA) is approximately 1-2 years, whilst poly(ɛ-caprolactone) (PCL) requires 2-4 years [1,67,68].”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [1] Woodruff, 2010, The return of a forgotten polymer—Polycaprolactone in the 21st century, Prog. Polym. Sci. source

      Section 3 (Biodegradation; page not provided) states that PCL homopolymer takes two to four years to degrade completely, depending on its starting molecular weight. The copy does not give a one-to-two-year complete-resorption time for PDLLA; Section 1 says only that PCL degrades more slowly than poly(D,L-lactide). (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [67] Middleton, 2000, Synthetic biodegradable polymers as orthopedic devices, Biomaterials source
    • cites [68] Maurus, 2004, Bioabsorbable implant material review, Oper. Tech. Sports Med. source

  • May combine two claims.

    Findingown data

    SEM micrographs revealed a high similarity of structure and consistency with the applied model.

    “SEM micrographs revealed a high similarity of structure and consistency with the applied model.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The midpoint glass transition temperatures (Tg) for LC16:4, 18:2 and 9:1 were 4.8, 31 and 33 °C respectively.

    “The midpoint glass transition temperatures (T g ) for LC16:4, 18:2 and 9:1 were 4.8, 31 and 33 °C respectively.”
    Quote in the paperNot a substantial claim

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

    Findingnone given

    The lower initiation limit of the polymerization with the UV source used appeared to be at 8-9 s, including the time needed for the lamp to develop full power.

    “The lower initiation limit of the polymerization with the UV source used appeared to be at 8-9 s, including the time needed for the lamp to develop full power.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    The molecular weight results for the LC scaffolds correlated with the monomer incorporation: LC18:2 and 9:1 showed higher values (see 3-5%) than theoretical molecular weights, while LC16:4 had 6% less than the predicted value.

    “This also correlated with the molecular weight results obtained for the LC scaffolds, as LC18:2 and 9:1 showed higher values (see 3-5%) than theoretical molecular weights, while LC16:4 had 6% less than the predicted value.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The pore sizes for all LC scaffolds were see 300 μm and throat sizes varied from 152 μm (for LC9:1) to 177 μm (for LC16:4 and 18:2).

    “The pore sizes for all LC scaffolds were see 300 μm and throat sizes varied from 152 μm (for LC9:1) to 177 μm (for LC16:4 and 18:2), see table 3.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Endothermic peaks were observed at 281 o C for LC16:4 and 365 °C for LC18:2 and 9:1, and represented decomposition temperature (Td).

    “Endothermic peaks were also observed at 281 o C for LC16:4 and 365 °C (see figure 7) for LC18:2 and 9:1, and represented decomposition temperature (T d ).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Initial increases were seen in the wet weight of LC16:4, 18:2 and 9:1 scaffolds respectively up to 5 (at 37 °C) and 2 d at 50 and 65 °C, followed by stabilisation in weights of all scaffolds.

    “Initial increases were seen in the wet weight of LC16:4, 18:2 and 9:1 scaffolds respectively up to 5 (at 37 °C) and 2 d at 50 and 65 °C, followed by stabilisation in weights of all scaffolds.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The lactide richer derivatives (9:1 and 18:2) tended to incorporate a lactide unit more than the target value, whereas the caprolactone richer LC16:4 had one LA unit less.

    “The lactide richer derivatives (9:1 and 18:2) tended to incorporate a lactide unit more than the target value, whereas the caprolactone richer LC16:4 had one LA unit less.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    The temperature dependency was most prominent in LC9:1, resulting in large steps between 30 °C and 70 °C, with a change in ΔH of see 25 J g -1 , compared with a change of <8 J g -1 for the other compositions.

    “The temperature dependency was most prominent in LC9:1, resulting in large steps between 30 °C and 70 °C, with a change in ΔH of see 25 J g -1 , compared with a change of <8 J g -1 for the other compositions.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Heating-cooling cycles covered a range of temperatures (37 °C-20 °C) which was around the glass transition temperature for LC18:2 and LC9:1 scaffolds, whilst Tg of LC16:4 was out of this range.

    “Heating-cooling cycles covered a range of temperatures (37 °C-20 °C) which was around their glass transition temperature for LC18:2 and 9:1 scaffolds, whilst T g of LC16:4 was out of this range.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    For commercialization, the writing time is still the main limitation; manufacturing scaffolds of one cubic centimeter with the current set-up would lead to writing times of about 6 d.

    “For commercialization, the writing time is still the main limitation, for example for manufacturing scaffolds of one cubic centimeter with the current set-up would lead to writing times of see 6 d.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Pore sizes were in the ideal range of 200-400 μm, known to facilitate osteo-differentiation and functional bone formation.

    “Pore sizes were in the ideal range of 200-400 μm, known to facilitate osteo-differentiation and functional bone formation [12,57,58].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [12] Tse, 2010, Preparation of hydrogel substrates with tunable mechanical properties, Curr Protoc. Cell Biol. source
    • cites [57] Papaioannou, 2006, Assessment of vascular wall shear stress and implications for atherosclerotic disease, Int. J. Cardiol. source
    • cites [58] Papaioannou, 2005, Vascular wall shear stress: basic principles and methods, Hellenic J. Cardiol.

      Not checked in the free run.

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

    Premisecitation

    The long wavelength of the NIR allows for deeper penetration into the material and thus structuring in millimeter dimensions and a submicron resolution.

    “The long wavelength of the NIR allows for deeper penetration into the material and thus structuring in millimeter dimensions and a submicron resolution (figure 1(A)) [23][24][25][26][27].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [23][24][25][26][27]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationreasoning

    LC9:1 generated more heat due to the [molecular weight]:[methacryl-group] ratio, resulting in a higher double bond density which correlated with the higher ΔH values.

    “LC9:1 generated more heat due to the [molecular weight]:[methacryl-group] ratio, resulting in a higher double bond density which correlated with the higher ΔH values.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    The main purpose of accelerated degradation studies is to attain degradation profiles within a shorter period of time and descriptive to that obtained at standard degradation conditions.

    “The main purpose of accelerated degradation studies is to attain degradation profiles within a shorter period of time and descriptive to that obtained at standard degradation conditions [35].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [35] Lam, 2008, Dynamics of in vitro polymer degradation of polycaprolactone-based scaffolds: accelerated versus simulated physiological conditions, Biomed. Mater. source

  • May combine two claims.

    Interpretationreasoning

    No crystallisation or melting peaks were detected for any of the scaffolds, possibly due to the high crosslinking in the photo-polymerisation process.

    “No crystallisation or melting peaks were detected for any of the scaffolds, possibly due to the high crosslinking in the photo-polymerisation process.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Incomplete chain-end-capping with methacrylate groups would consequently affect the mechanical properties, cause local acidification and fast degradation of the LC chains.

    “This would consequently affect the mechanical properties, cause local acidification and fast degradation of the LC chains due to the lack of complete chain-end-capping with methacrylate groups [54].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [54] Burdick, 2003, An initial investigation of photocurable 3D lactic acid based scaffolds in a critical-sized cranial defect, Biomaterials source

  • Classified as probably not a substantial claim.

    Premisecitation

    Higher resolutions can be obtained by using two-photon absorption (TPA) where excitation wavelengths in the near-infrared (NIR) were used in combination with femtosecond pulsed lasers.

    “Higher resolutions can be obtained by using two-photon absorption (TPA) where excitation wavelengths in the near-infrared (NIR) were used in combination with femtosecond pulsed lasers [18][19][20].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [18][19][20]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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

    Study design and conductcitation

    Writing parameters were kept constant for all scaffolds since they can influence the mechanical properties and degradation of the resulting polymer structures.

    “Writing parameters were kept constant for all scaffolds since they can influence the mechanical properties and degradation of the resulting polymer structures [59].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [59] Farkas, 2015, Four-order stiffness variation of laser-fabricated photopolymer biodegradable scaffolds by laser parameter modulation, Mater. Sci. Eng. C source

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

    Interpretationcitation

    The higher temperature dependency of LC9:1 could have been related to the higher amount of double bonds present and the accessibility of these with increase in temperature and subsequent reduction in viscosity.

    “This could have been related to the higher amount of double bonds present and the accessibility of these with increase in temperature and subsequent reduction in viscosity [55].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [55] Tobita, 1998, Molecular weight distribution formed through chain-length-dependent crosslinking reactions, Macromol. Theory Simul. source

  • Classified as probably not a substantial claim.

    Premisecitation

    Relating accelerated degradation at elevated temperatures to 37 °C allows effective fast screening rather than long term studies saving research funds and time.

    “Relating accelerated degradation at elevated temperatures to 37 °C allows effective fast screening rather than long term studies saving research funds and time [34].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [34] Pietrzak, 2003, The influence of temperature on the degradation rate of lactosorb copolymer, J. Craniofac. Surg. source

  • May combine two claims.

    Interpretationcitation

    A second phase of increase in the scaffold weights was seen after 25 and 6 d of degradation at 50 and 65 °C respectively, which was a consequence of imbalance between water uptake and mass loss (i.e. mass loss due to hydrolytic degradation became dominant).

    “In contrast, a second phase of increase in the scaffold weights was seen after 25 and 6 d of degradation at 50 and 65 °C respectively, which was a consequence of imbalance between water uptake and mass loss (i.e.mass loss due to hydrolytic degradation became dominant) [38].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [38] Felfel, 2015, Accelerated in vitro degradation properties of polylactic acid/phosphate glass fibre composites, J. Mater. Sci. source

  • May combine two claims.

    Interpretationown data

    The calculations of conversions revealed the high reactivity and large differences between temperatures for LC9:1, which are a result of its incomplete conversion at low temperatures (less than 70%).

    “The calculations of conversions revealed the high reactivity and large differences between temperatures for LC9:1, which are a result of its incomplete conversion at low temperatures (less than 70%).”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Validated accelerated degradation studies are an attractive research tool to explore the influence of the physico-chemical factors as well as other influences such as initiators and polymer blends.

    “Therefore, validated accelerated degradation studies are an attractive research tool [38] to explore the influence of the physico-chemical factors as well as other influences such as initiators and polymer blends.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [38] Felfel, 2015, Accelerated in vitro degradation properties of polylactic acid/phosphate glass fibre composites, J. Mater. Sci. source

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

    Premisecitation

    Body temperature varies significantly between human and certain animals such as pigs and rabbits (approximately 1-3 °C higher than humans) which are commonly used as in vivo models.

    “Moreover, body temperature varies significantly between human and certain animals such as pigs and rabbits (approximately 1-3 °C higher than humans) which are commonly used as in vivo models [34].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [34] Pietrzak, 2003, The influence of temperature on the degradation rate of lactosorb copolymer, J. Craniofac. Surg. source

  • May combine two claims.

    Interpretationcitation

    Values of Tg and Td for LC18:2 and 9:1 were similar, whilst LC16:4 showed significantly lower results, which was ascribed to the variation in D,L lactide ratio to ɛ-caprolactone (LA/CL) ratio in different scaffolds.

    “Values of T g and T d for LC18:2 and 9:1were similar, whilst LC16:4 showed significantly lower results, which was ascribed to the variation in D,L lactide ratio to ɛ-caprolactone (LA/CL) ratio in different scaffolds [65,66] (see table 2).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [65] Fernández, 2013, A new generation of poly(lactide/ε-caprolactone) polymeric biomaterials for application in the medical field, J. Biomed. Mater. Res. A source
    • cites [66] Fernández, 2012, Synthesis, structure and properties of poly(L-lactide-co--caprolactone) statistical copolymers, J. Mech. Behav. Biomed. Mater. source

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

    Premisecitation

    The degradation rate of degradable polymers is controlled by numerous factors such as degree of crystallinity, chemical structure, molecular weight, porosity, surface/volume ratio, manufacturing methods, implantation site, applied load, degradation temperature and pH of the degradation medium.

    “The degradation rate of degradable polymers is controlled by numerous factors such as degree of crystallinity, chemical structure, molecular weight, porosity, surface/volume ratio, manufacturing methods, implantation site, applied load, degradation temperature and pH of the degradation medium [34][35][36][37].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [34][35][36]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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

    Interpretationnone given

    The deviation of pore geometry from spherical to ellipsoidal was suggested to be due to the refractive stretching of the precursor along Z-direction.

    “This was suggested to be due to the refractive stretching of the precursor along Z-direction.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Claes et al found that PLA pins completely lost their flexural strength after 18 months and 96 h of immersion in NaCl at 37 °C and 70 °C respectively.

    “They found that the pins completely lost their flexural strength after 18 months and 96 h of immersion in NaCl at 37 °C and 70 °C respectively.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [39] Claes, 1996, New bioresorbable pin for the reduction of small bony fragments: design, mechanical properties and in vitro degradation, Biomaterials source

  • May combine two claims.

    Premisecitation

    Variation in the methacrylation could lead to less stable structures, more unsolidified residues in the material and open chain ends after photochemical vitrification.

    “Variation in the methacrylation could lead to less stable structures, more unsolidified residues in the material and open chain ends after photochemical vitrification.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [54] Burdick, 2003, An initial investigation of photocurable 3D lactic acid based scaffolds in a critical-sized cranial defect, Biomaterials source

  • May combine two claims.

    Interpretationown data

    At low temperatures the conversion was the lowest for all precursors, an effect reversed at 70 °C, a temperature at which the motility (molecule size) is a function of conversion.

    “At low temperatures the conversion was the lowest for all precursors, an effect reversed at 70 °C, a temperature at which the motility (molecule size) is a function of conversion.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Gamma sterilisation is known to induce molecular changes for polymeric materials by chain scission and crosslinking.

    “However, gamma sterilisation is known to induce molecular changes for polymeric materials by chain scission and crosslinking [61][62][63].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [61][62][63]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationreasoning

    These materials have the potential to replace state-of-the-art implants and allografts as they can offer slower degradation and softer mechanics and avoid the acidity-burst at degradation compared to LA.

    “These materials have the potential to replace state-of-theart implants and allografts as they can offer slower degradation and softer mechanics and avoid the acidity-burst at degradation compared to LA”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    Degradation and compression tests were completed at day 90 and 83 respectively because LC18:2 and 9:1 scaffolds became brittle and difficult to handle for weighing and mechanical testing.

    “The degradation and compression tests were completed at day 90 and 83 respectively because the LC18:2 and 9:1 scaffolds became brittle and difficult to handle for weighing and mechanical testing.”
    Quote in the paperNot a substantial claim

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

    Premisenone given

    Previous studies have suggested that degradation activation energies were independent of the geometry and composition of the PLLA-PGA copolymers.

    “Previous studies have suggested that degradation activation energies were independent of the geometry and composition of the PLLA-PGA copolymers.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Accelerated degradation tests can be afforded an expectation of degradation profiles in a short period of time by correlating the results of the 70 °C test with that obtained at 37 °C.

    “It was concluded that accelerated degradation tests can be afforded an expectation of degradation profiles in a short period of time by correlating the results of the 70 °C test with that obtained at 37 °C.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [39] Claes, 1996, New bioresorbable pin for the reduction of small bony fragments: design, mechanical properties and in vitro degradation, Biomaterials source

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

    Premisecitation

    A rapid loss of tensile strength was seen for PGLA multifilament braids degraded at higher temperatures.

    “A rapid loss of tensile strength was seen for specimens degraded at higher temperatures.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [40] Deng, 2005, Effect of load and temperature on in vitro degradation of poly(glycolide-co-L-lactide) multifilament braids, Biomaterials source

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

    Premisecitation

    Pietrzak et al. applied the Arrhenius equation to change in inherent viscosity for a 82%PLLA-18%PGA copolymer and obtained an activation energy of 100.1 kJ mol−1.

    “Pietrzak et al [34] applied the Arrhenius equation to change in inherent viscosity for a 82%PLLA-18%PGA copolymer and obtained an activation energy of 100.1 kJ”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [34] Pietrzak, 2003, The influence of temperature on the degradation rate of lactosorb copolymer, J. Craniofac. Surg. source

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

    Premisecitation

    Weir et al. and Agrawal et al. determined activation energies for 50%PLA-50%PGA copolymer and PLLA (113.9 and 100.5 kJ mol−1) through the change in molecular weight against degradation temperature.

    “Weir et al [49] and Agrawal et al [71] determined activation energies for 50%PLA-50%PGA copolymer and PLLA (113.9 and 100.5 kJ mol -1 ) through the change in molecular weight against degradation temperature.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [49] Weir, 2004, Degradation of poly-L-lactide. Part 2: increased temperature accelerated degradation, Proc. Inst. Mech. Eng. H source
    • cites [71] Agrawal, 1997, Elevated temperature degradation of a 50:50 copolymer of PLA-PGA, Tissue Eng. source

  • May combine two claims.

    Interpretationown data

    Mechanical properties of these scaffolds were mainly dependent on their material composition (LA/CL ratio) as all scaffolds have almost the same porosity and pore sizes.

    “Mechanical prop-erties of these scaffolds were mainly dependent on their material composition (i.e.LA/CL ratio) as all scaffolds have almost the same porosity and pore sizes.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    The time required to reach a given breaking strength at different temperature followed an Arrhenius equation and the activation energies calculated were 96.12 to 102.38 kJ mol -1.

    “The time required to reach a given breaking strength at different temperature followed an Arrhenius equation and the activation energies calculated were 96.12 to 102.38 kJ mol -1 .”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [40] Deng, 2005, Effect of load and temperature on in vitro degradation of poly(glycolide-co-L-lactide) multifilament braids, Biomaterials source

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

    Premisecitation

    Arrhenius relation has been conducted for the change in several parameters of biodegradable polymers such as molecular weight, breaking strength, viscosity and mass loss.

    “Arrhenius relation has been conducted for the change in several parameters of biodegradable polymers such as molecular weight, breaking strength, viscosity and mass loss [34,38,49,71,72].”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [34] Pietrzak, 2003, The influence of temperature on the degradation rate of lactosorb copolymer, J. Craniofac. Surg. source
    • cites [38] Felfel, 2015, Accelerated in vitro degradation properties of polylactic acid/phosphate glass fibre composites, J. Mater. Sci. source
    • cites [49] Weir, 2004, Degradation of poly-L-lactide. Part 2: increased temperature accelerated degradation, Proc. Inst. Mech. Eng. H source
    • cites [71] Agrawal, 1997, Elevated temperature degradation of a 50:50 copolymer of PLA-PGA, Tissue Eng. source
    • cites [72] Deng, 2008, A study on in vitro degradation behavior of a poly(glycolide-co-l-lactide) monofilament, Acta Biomater. source

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

    Premisecitation

    Degradation activation energy was also determined for 10%PLLA-90%PGA through change in tensile breaking strength during degradation at different temperatures, and the activation energy ranged between 95.9 and 102.6 kJ mol−1.

    “Degradation activation energy was also determined for 10%PLLA-90%PGA through change in tensile breaking strength during degradation at different temperatures [40].The activation energy ranged between 95.9 kJ mol -1 and 102.6 kJ mol -1 .”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [40] Deng, 2005, Effect of load and temperature on in vitro degradation of poly(glycolide-co-L-lactide) multifilament braids, Biomaterials source

  • May combine two claims.

    Premisecitation

    Tensile modulus and strength of the copolymer films decreased from 1343 to 12 MPa and from 26.6 to 17.2 MPa respectively as the CL contents increased from 10 to 30%.

    “Tensile modulus and strength of the copolymer films decreased from 1343 to 12 MPa and from 26.6 to 17.2 MPa respectively as the CL contents increased from 10 to 30%.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [66] Fernández, 2012, Synthesis, structure and properties of poly(L-lactide-co--caprolactone) statistical copolymers, J. Mech. Behav. Biomed. Mater. source

  • May combine two claims.

    Interpretationown data

    The onset glass transition for LC16:4 scaffolds (-1.6 ± 1 °C) was significantly lower than the testing temperature, and this explained the lower variation in results showing a smooth and gradual decrease in their compressive modulus and strength properties.

    “The onset glass transition for LC16:4 scaffolds (-1.6 ± 1 °C) was significantly lower than the testing temperature and this explained the lower variation in results showing a smooth and gradual decrease in their compressive modulus and strength properties (inset, figures 11 (A) and (B)).”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Similar findings were published for poly(L-lactide-co-ε-caprolactone) copolymers by Fernandez et al.

    “Similar findings were published for poly(L-lactide-co-ε-caprolactone) copolymers by Fernandez et al [66].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [66] Fernández, 2012, Synthesis, structure and properties of poly(L-lactide-co--caprolactone) statistical copolymers, J. Mech. Behav. Biomed. Mater. source

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

    Premisecitation

    Tensile strength of PGLA braids decreased by ~10% after soaking in PBS for 10 d at 47.5 °C, whereas 30 d were required to reach 10% loss in the strength at 37 °C.

    “Tensile strength of the braids decreased by ~10% after soaking in PBS for 10 d at 47.5 °C.However, 30 d were required to reach 10% loss in the strength at 37 °C.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [40] Deng, 2005, Effect of load and temperature on in vitro degradation of poly(glycolide-co-L-lactide) multifilament braids, Biomaterials source
52 of 52

  • The paper relies on this without support.

    Complex architectures with specifically controlled micro- and macro-scale features are difficult to achieve using traditional scaffold fabrication techniques.

    “However, complex architectures with specifically controlled micro-and macro-scale features have been difficult to achieve.”

  • The paper relies on this without support.

    The rate of hydrolysis of biodegradable polymers increases with degradation temperature, making correlation between short-term high-temperature and long-term physiological-temperature degradation achievable.

    “The rate of hydrolysis is known to increase with degradation temper ature which would potentially make the correlation between short-term effects at high temperature and long-term effects at physiological temperature achievable.”

  • The paper relies on this without support.

    Degradable devices can take up to several years for complete degradation at physiological temperature (37 °C), depending on the polymer and geometry.

    “Depending on the polymer and geometry, degradable devices can take up to several years for complete degradation at physiological temperature (37 °C).”

  • The paper relies on this without support.

    Schwarz Primitive minimal surface derived unit cells potentially have higher load-bearing capacities due to their strain distribution.

    “The 3D scaffold structures were based on a Schwarz Primitive (P) minimal surface derived unit cells which potentially have higher loadbearing capacities due to their strain distribution.”

  • The paper relies on this without support.

    For two-photon polymerization, only optically transparent materials are suitable, and materials with higher caprolactone contents tend to form optical disturbing crystallites at room temperature.

    “For TPP, only optical transparent materials are suitable and materials with higher caprolactone contents tending to form optical disturbing crystallites at room temperature.”

  • The paper relies on this without support.

    The relative monomer contents of LC render the polymer more hydrophilic or hydrophobic and influence the degradation rate, viscosity of the precursor, mechanical behavior of the cross-linked and solidified material and degradation behaviour.

    “Their relative monomer contents render the polymer more hydrophilic or hydrophobic and influence the degradation rate, viscosity of the precursor and mechanical behavior of the cross-linked and solidified material and degradation behaviour.”

  • The paper relies on this without support.

    The surface area/volume ratio of the scaffolds depends on pore size, and the degradation rate of scaffolds is expected to increase as the surface area/volume ratio increases.

    “Note the surface area/ volume ratio of the scaffolds depends on pore size and the degradation rate of scaffolds is expected to increase as the surface area/volume ratio increased.”
7 of 7

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.

  • Reported pore aspect ratios exceed their defined maximum

    Minor

    The paper defines pore aspect ratio as the minor axis divided by the major axis, which cannot exceed 1. Table 3 reports values above 1 for every scaffold type.

  • Compression-test standard points to the wrong reference

    Minor

    The methods cite reference 51 for the ASTM compression-test standard, but reference 51 is a chemistry paper; the ASTM standard appears as reference 50.

  • Activation-energy units disagree within the paper

    Minor

    The methods assign activation energy units containing inverse kelvin, but the results report activation energies without that temperature dimension.

  • A modulus value is assigned to an unlisted scaffold composition

    Minor

    The initial compressive-modulus statement assigns the third value to LC9:2, whereas the study identifies that scaffold as LC9:1.

4 of 4

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Authors
Felfel, R. M., Poocza, L., Gimeno-Fabra, M., Milde, T., Hildebrand, G., Ahmed, I., Scotchford, C., Sottile, V., Grant, D. M., & Liefeith, K.
Affiliations
  • University of Nottingham (GB)
  • Institute for Bioprocessing and Analytical Measurement Techniques (DE)
Corresponding author
  • Grant, David M
  • Liefeith, Klaus
ORCID
Venue
Biomedical Materials
Publisher
IOP Publishing
Published
2016-02-01
Volume
11
Issue
1
Pages
015011
ISSN
  • 1748-6041 (ISSN-L)
  • 1748-605X
DOI
10.1088/1748-6041/11/1/015011
OpenAlex
W2272323856
Cited by
103
References
74
Citations by year
2026: 2 · 2025: 8 · 2024: 5 · 2023: 12 · 2022: 10 · 2021: 12 · 2020: 16 · 2019: 11 · 2018: 11 · 2017: 11 · 2016: 3
FWCI
5.13
Type
journal article
Language
en
Open access
Licence
Locations
  • Biomedical Materials (publishedVersion)
  • PubMed (publishedVersion)
  • Nottingham ePrints (University of Nottingham) (submittedVersion, cc-by)
  • Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
Funders
European Union’s Seventh Framework Programme (263363)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
  • Physical Sciences › Materials Science › Biomaterials › biodegradable polymer synthesis and properties
  • Physical Sciences › Engineering › Biomedical Engineering › Nonlinear Optical Materials Studies
Keywords
two-photon polymerization, 3D scaffolds, in vitro degradation, mechanical properties, compressive strength, mass loss, glass transition temperature, activation energy of degradation
MeSH terms
Equipment Design, Light, Materials Testing, Polyesters, Polymers

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

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