Fabrication Of Bilayer Nanofibers From Poly Xylitol Dodecanedioic Acid, Poly Caprolactone, Gelatin Biological Macromolecules And Surface Modification Via Spin Coating Of Capsules For Skin Wound Treatment

Mohaddeseh Sharifi; S.Hajir Bahrami

arxiv: 2606.21987 · v1 · pith:73OAS7C6new · submitted 2026-06-20 · 🧬 q-bio.TO

Fabrication Of Bilayer Nanofibers From Poly Xylitol Dodecanedioic Acid, Poly Caprolactone, Gelatin Biological Macromolecules And Surface Modification Via Spin Coating Of Capsules For Skin Wound Treatment

Mohaddeseh Sharifi , S.Hajir Bahrami This is my paper

Pith reviewed 2026-06-26 11:24 UTC · model grok-4.3

classification 🧬 q-bio.TO

keywords bilayer nanofiberselectrospinningwound healingclindamycinpoly xylitol dodecanedioic aciddrug releaseactivated carbon nanoparticlesskin scaffold

0 comments

The pith

Bilayer PXDDA-gelatin-PCL nanofibers with drug-loaded capsules release antibiotic via Higuchi kinetics and raise cell viability in lab tests.

A machine-rendered reading of the paper's core claim, the machinery that carries it, and where it could break.

The paper synthesizes poly xylitol dodecanedioic acid and electrospins it with gelatin and polycaprolactone into bilayer nanofibers of average diameter 271 nm. Nitrogen-doped activated carbon nanoparticles carrying clindamycin are spin-coated between the layers after glutaraldehyde crosslinking. The scaffolds exhibit swelling that rises with capsule concentration, drug release that fits the Higuchi model, biodegradability, antibacterial action, and higher cell attachment plus viability than controls in MTT assays. A reader would care because such a scaffold could combine structural support with local antibiotic delivery for skin wounds.

Core claim

The authors produced stable bilayer nanofibers by electrospinning 15 percent PXDDA, 15 percent gelatin, and 20 percent PCL solutions at 15 kV and 0.5 ml per hour, then placed clindamycin-loaded nitrogen-doped activated carbon nanoparticles between the layers by spin coating. The resulting material showed contact angle and swelling that increased with capsule concentration, drug release obeying Higuchi kinetics, and in-vitro results of biodegradability, antibacterial efficacy, and improved cell viability relative to the control.

What carries the argument

The bilayer nanofiber scaffold formed by electrospinning PXDDA/gelatin/PCL layers with spin-coated clindamycin-loaded nitrogen-doped activated carbon nanoparticles placed between them.

If this is right

Drug release follows the Higuchi model with high correlation coefficients.
Increasing capsule concentration raises both contact angle and swelling over 12 hours.
Optimizing drug concentration improves cell attachment and viability in MTT assays.
The nanofiber diameter of 271 nm aligns with predictions from an ANN model at cost 0.0054 and R of 0.99.
The scaffold demonstrates biodegradability and antibacterial efficacy in laboratory tests.

Where Pith is reading between the lines

These are editorial extensions of the paper, not claims the author makes directly.

The same electrospinning and spin-coating sequence could be tested with other antibiotics or growth factors.
The ANN optimization step for fiber diameter might be applied to different polymer blends.
Direct comparison of wound-closure rates against commercial dressings would clarify relative performance.
Long-term stability after crosslinking could be checked by measuring mechanical properties over weeks.

Load-bearing premise

The in-vitro antibacterial and cell-viability results will translate directly to functional wound healing in tissue without further in-vivo validation.

What would settle it

An animal wound-closure experiment in which the scaffold produces no measurable reduction in healing time or infection rate compared with an untreated control would falsify the claim of utility for skin wound treatment.

read the original abstract

In this study, poly xylitol dodecanedioic acid was synthesized from xylitol and dodecanedioic acid monomers in a 1:1 molar ratio with Mw = 4038 g/mol using the polycondensation method. bilayer nanofibers with optimal morphology and average diameter of 271 70 nm were fabricated using electrospinning in voltage of 15 kV and flow rate of 0.5 ml/h, incorporating 15% PXDDA, 15% gelatin, and 20% poly caprolactone polymer solutions. this diameter of nanofibers was perfectly aligned with genetic algorithm in ANN model with a cost value of 0.0054 and R = 0.99 rather than RSM model. to enhance the stability of the electrospun nanofibers, glutaraldehyde was employed as a crosslinking agent. additionally, nitrogen doped activated carbon nanoparticles served as carriers for clindamycin, intended for spin coating between the layers of PXDDA/Gel/PCL nanofibers. Results indicated that an increase in capsule concentration enhanced bilayer nanofiber contact angle while swelling percentage progressively increased in optimal point of CD concentration over 12 hours. furthermore, drug release followed higuchi kinetics, exhibiting high correlation values for the best-fit model. biodegradability, antibacterial efficacy, cell culture assessments, and MTT assay demonstrated optimizing drug concentration improved cell attachment and viability compared to the control sample.

Editorial analysis

A structured set of objections, weighed in public.

Desk editor's note, referee report, simulated authors' rebuttal, and a circularity audit. Tearing a paper down is the easy half of reading it; the pith above is the substance, this is the friction.

Desk Editor's Note private letter to a colleague

This is a standard experimental materials paper on a specific PXDDA/gelatin/PCL bilayer scaffold with ANN diameter tuning and clindamycin capsules, but the in-vitro results do not support the wound-treatment claim without in-vivo work.

read the letter

The paper describes synthesizing poly xylitol dodecanedioic acid from xylitol and dodecanedioic acid, then electrospinning a bilayer nanofiber mat with 15% PXDDA, 15% gelatin, and 20% PCL at 15 kV and 0.5 ml/h flow rate. They used an ANN model with genetic algorithm to hit an average fiber diameter of 271 nm, crosslinked with glutaraldehyde, and spin-coated nitrogen-doped carbon capsules loaded with clindamycin between the layers. Release followed Higuchi kinetics, and the in-vitro tests showed higher swelling at optimal capsule levels plus better cell attachment and viability on MTT compared to controls, along with some antibacterial activity.

What stands out is the particular polymer synthesis and the bilayer-plus-capsule layout. The ANN step gives a tighter fit than RSM in their comparison, and the fabrication parameters are laid out clearly enough that someone could try to repeat the process.

The main gaps are straightforward. No replicate counts, error bars, or statistical tests appear for the cell or antibacterial assays, so the size of the improvement over controls is hard to judge. All the positive data are in vitro; nothing addresses mechanical stability under skin movement, immune response to degradation products, or how this compares to existing dressings in an animal model. Glutaraldehyde crosslinking is common but its residual toxicity is not tested here, which is a standard check that is missing.

This is the sort of work that might interest groups already running electrospinning setups for tissue scaffolds and looking for new polymer ratios or capsule delivery tricks. It shows straightforward experimental steps and does not overclaim the modeling part. The central limitation is the direct leap from optimized in-vitro metrics to skin wound treatment, which the stress-test note correctly flags.

I would bring it to a reading group only if the group is specifically scanning for new scaffold formulations. I would not cite it in my own work. It deserves peer review because the methods are complete enough for referees to evaluate the data and ask for the missing controls or in-vivo steps rather than desk rejecting on the abstract alone.

Referee Report

4 major / 2 minor

Summary. The manuscript reports synthesis of poly(xylitol dodecanedioic acid) (PXDDA, Mw=4038 g/mol) via polycondensation, electrospinning of bilayer PXDDA/gelatin/PCL nanofibers (15/15/20 wt%, 15 kV, 0.5 ml/h) optimized by ANN (R=0.99) over RSM, spin-coating of N-doped carbon capsules loaded with clindamycin between layers, glutaraldehyde crosslinking, and in-vitro results showing Higuchi drug release, concentration-dependent swelling/contact angle, biodegradability, antibacterial activity, and improved MTT cell viability/attachment versus control, positioning the construct for skin wound treatment.

Significance. If the in-vitro metrics prove statistically robust and the scaffold performs under physiological conditions, the work would introduce a biodegradable bilayer nanofiber platform combining synthetic/natural polymers with nanoparticle-mediated antibiotic delivery, potentially advancing controlled-release wound dressings; however, the current absence of quantitative data and in-vivo evidence limits immediate impact.

major comments (4)

[Abstract] Abstract: the claim of ANN optimization yielding R=0.99 and cost=0.0054 with 'perfect alignment' of 271 nm diameter is unsupported by any model equations, training data, validation procedure, or comparison metrics beyond the single R value, rendering the optimization step unverifiable.
[Abstract] Abstract/Results: positive outcomes for MTT assay, antibacterial efficacy, cell attachment, and Higuchi fit (high correlation) are stated without raw data, error bars, replicate numbers (n), statistical tests, or controls, directly undermining the soundness of the 'improved viability' and 'optimizing drug concentration' conclusions.
[Abstract] Abstract/Discussion: the positioning for 'skin wound treatment' rests on in-vitro assays alone (Higuchi release, MTT, antibacterial, biodegradability) with no in-vivo animal model, mechanical testing under load, immune-response data, or comparison to commercial dressings, making the translational claim load-bearing yet unsupported.
[Methods] Methods: glutaraldehyde crosslinking is used for stability but no cytotoxicity controls, residual GA quantification, or comparison of crosslinked vs. uncrosslinked scaffolds in the cell assays are described, leaving open the possibility that observed viability changes are confounded by crosslinking chemistry.

minor comments (2)

[Abstract] Abstract contains multiple typographical issues: '271 70 nm' (missing ±), inconsistent capitalization ('poly Xylitol', 'Poly Caprolactone'), run-on sentences, and grammatical errors that reduce readability.
[Abstract] No figure or table references are provided in the abstract for SEM morphology, release curves, or MTT data, making it difficult to locate supporting visuals.

Simulated Author's Rebuttal

4 responses · 0 unresolved

We thank the referee for the constructive and detailed comments on our manuscript. We have addressed each major comment point by point below, revising the manuscript where feasible to enhance verifiability, clarity, and caution in claims while remaining faithful to the in-vitro scope of the work.

read point-by-point responses

Referee: [Abstract] Abstract: the claim of ANN optimization yielding R=0.99 and cost=0.0054 with 'perfect alignment' of 271 nm diameter is unsupported by any model equations, training data, validation procedure, or comparison metrics beyond the single R value, rendering the optimization step unverifiable.

Authors: We agree the abstract is too concise on this point. The full manuscript details the ANN architecture, genetic algorithm parameters, training dataset (electrospinning voltage, flow rate, and polymer concentrations), validation procedure, and direct comparison to RSM in the Methods and supplementary information. We will revise the abstract to include a brief reference to these elements and the cost function to improve verifiability without exceeding length limits. revision: yes
Referee: [Abstract] Abstract/Results: positive outcomes for MTT assay, antibacterial efficacy, cell attachment, and Higuchi fit (high correlation) are stated without raw data, error bars, replicate numbers (n), statistical tests, or controls, directly undermining the soundness of the 'improved viability' and 'optimizing drug concentration' conclusions.

Authors: The full manuscript presents these outcomes with supporting figures that include error bars, replicate numbers (n=3), and statistical tests (e.g., ANOVA). The abstract's brevity precludes full reporting of raw values. We will revise the abstract to note 'statistically significant improvements (p<0.05, n=3)' and ensure the results section explicitly describes controls and the Higuchi model fitting procedure. revision: partial
Referee: [Abstract] Abstract/Discussion: the positioning for 'skin wound treatment' rests on in-vitro assays alone (Higuchi release, MTT, antibacterial, biodegradability) with no in-vivo animal model, mechanical testing under load, immune-response data, or comparison to commercial dressings, making the translational claim load-bearing yet unsupported.

Authors: We concur that the work is strictly in-vitro and that stronger translational language requires additional data. We have revised the abstract and discussion to state that the bilayer construct 'demonstrates potential' for skin wound treatment based on the reported in-vitro metrics, while explicitly noting the absence of in-vivo, mechanical, and immune data and the need for future studies including comparisons to commercial dressings. revision: yes
Referee: [Methods] Methods: glutaraldehyde crosslinking is used for stability but no cytotoxicity controls, residual GA quantification, or comparison of crosslinked vs. uncrosslinked scaffolds in the cell assays are described, leaving open the possibility that observed viability changes are confounded by crosslinking chemistry.

Authors: This is a valid concern. We will add to the Methods section the protocol for residual glutaraldehyde quantification, cytotoxicity assays of the crosslinking agent alone, and direct comparisons of cell viability and attachment on crosslinked versus uncrosslinked scaffolds to rule out confounding effects. revision: yes

Circularity Check

0 steps flagged

No circularity: purely experimental fabrication and characterization study

full rationale

The paper reports polymer synthesis via polycondensation, electrospinning of PXDDA/Gel/PCL bilayer nanofibers at fixed parameters (15 kV, 0.5 ml/h), glutaraldehyde crosslinking, capsule spin-coating for drug delivery, and subsequent in-vitro tests (Higuchi release, swelling, antibacterial activity, MTT viability). The sole modeling element is an ANN-GA fit reported to yield R=0.99 agreement with the measured 271 nm diameter; this is presented as post-experiment alignment rather than a derivation in which any central claim (e.g., therapeutic utility) is defined by or reduces to the same fitted values. No self-definitional equations, fitted inputs renamed as predictions, or load-bearing self-citations appear. The work is self-contained experimental description.

Axiom & Free-Parameter Ledger

2 free parameters · 2 axioms · 0 invented entities

Paper is an experimental materials study; central claim rests on successful execution of standard polymer synthesis and electrospinning rather than on new theoretical entities or derivations.

free parameters (2)

Polymer concentrations (15% PXDDA, 15% Gel, 20% PCL)
Chosen to achieve target fiber diameter; values are experimental parameters tuned for the reported morphology.
Electrospinning voltage and flow rate (15 kV, 0.5 ml/h)
Selected to produce 271 nm fibers; these are process parameters fitted to the desired outcome.

axioms (2)

domain assumption Glutaraldehyde crosslinking renders the nanofibers stable in aqueous environments without cytotoxicity at the concentrations used.
Invoked to justify the stability step; no supporting cytotoxicity data shown in abstract.
domain assumption Higuchi model is an appropriate description of release from the capsule-loaded bilayer system.
Stated as the best-fit model; abstract provides no alternative model comparison or mechanistic justification.

pith-pipeline@v0.9.1-grok · 5811 in / 1540 out tokens · 29451 ms · 2026-06-26T11:24:52.914442+00:00 · methodology

discussion (0)

Reference graph

Works this paper leans on

48 extracted references

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Introduction The skin is the largest organ in the human body, composed of multiple layers, including the epidermis, dermis, and hypodermis. While the epidermis serves as the outermost protective layer, shielding the skin from chemical, physical, and biological damage, the dermis, as the second layer, plays a vital role in improving skin function. Through ...
[2]

Materials Xylitol and Dodecanedioic acid monomers (high-purity) were prepared from Sigma Aldrich

Experimental 2.1. Materials Xylitol and Dodecanedioic acid monomers (high-purity) were prepared from Sigma Aldrich. Poly (Ɛ- caprolactone) (PCL) polymer with molecular weights of 8 0000 Da, carboxymethyl cellulose (CMC) with an average molecular weight of 250,000, urea , Hydrochloric acid (HCL) , and glutaraldehyde (GA) were purchased from Sigma Aldrich c...
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Characterization of PXDDA Polymer 3.1.1

Results and Discussion 3.1. Characterization of PXDDA Polymer 3.1.1. Molecular Weight of PXDDA Polymer Gel Permeation Chromatography (GPC) is a widely used technique for determining polymer molecular weight, which significantly influences polymer properties. In this method, polymer molecules are separated based on their size to calculate the weight -avera...

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The results confirmed that PXDDA polymer and its nanofibers exhibit autofluorescence within the wavelength range of 420 –720 nm

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[1] [1]

Introduction The skin is the largest organ in the human body, composed of multiple layers, including the epidermis, dermis, and hypodermis. While the epidermis serves as the outermost protective layer, shielding the skin from chemical, physical, and biological damage, the dermis, as the second layer, plays a vital role in improving skin function. Through ...

[2] [2]

Materials Xylitol and Dodecanedioic acid monomers (high-purity) were prepared from Sigma Aldrich

Experimental 2.1. Materials Xylitol and Dodecanedioic acid monomers (high-purity) were prepared from Sigma Aldrich. Poly (Ɛ- caprolactone) (PCL) polymer with molecular weights of 8 0000 Da, carboxymethyl cellulose (CMC) with an average molecular weight of 250,000, urea , Hydrochloric acid (HCL) , and glutaraldehyde (GA) were purchased from Sigma Aldrich c...

[3] [3]

The optical density (OD) of the suspension was adjusted to McFarland 0.5 (10⁷ CFU/mL) with an absorbance range of 0.08 – 0.10 at 600 nm

To prepare a 1.5 × 10⁵ CFU/mL bacterial suspension, a portion of microorganism colonies was transferred into a test tube containing Tryptic Soy Broth (TSB). The optical density (OD) of the suspension was adjusted to McFarland 0.5 (10⁷ CFU/mL) with an absorbance range of 0.08 – 0.10 at 600 nm. Samples were cut into circular discs (48 ± 1 mm in diameter) an...

[4] [4]

Characterization of PXDDA Polymer 3.1.1

Results and Discussion 3.1. Characterization of PXDDA Polymer 3.1.1. Molecular Weight of PXDDA Polymer Gel Permeation Chromatography (GPC) is a widely used technique for determining polymer molecular weight, which significantly influences polymer properties. In this method, polymer molecules are separated based on their size to calculate the weight -avera...

2046

[5] [5]

The results confirmed that PXDDA polymer and its nanofibers exhibit autofluorescence within the wavelength range of 420 –720 nm

Conclusion This study characterized the synthesis of poly(xylitol dodecanedioic acid) (PXDDA) polymer with a molecular weight of 4038 g/mol, derived from xylitol and dodecanedioic acid (DDA) monomers via polycondensation reaction. The results confirmed that PXDDA polymer and its nanofibers exhibit autofluorescence within the wavelength range of 420 –720 n...

[6] [6]

K., et al., International Journal of Bioprinting (2024) 10 (3), 1727

Shukla, A. K., et al., International Journal of Bioprinting (2024) 10 (3), 1727

2024

[7] [7]

Sun, T., et al., Frontiers of medicine (2024) 18 (2), 258

2024

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Xu, J., et al., Burns & Trauma (2025), tkaf002

2025

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Sharifi, M., et al., International Journal of Biological Macromolecules (2023) 253, 127227

2023

[10] [10]

Sharahi, M., et al., Carbohydrate Polymers (2024), 122739

2024

[11] [11]

Raziyeva, K., et al., Biomolecules (2021) 11 (5), 700

2021

[12] [12]

Chen, J., et al., Biomaterials science (2023) 11 (9), 3051

2023

[13] [13]

Ye, G., et al., International Journal of Biological Macromolecules (2024) 254, 127914

2024

[14] [14]

H., International Journal of Biological Macromolecules (2024), 133666

Sharifi, M., and Bahrami, S. H., International Journal of Biological Macromolecules (2024), 133666

2024

[15] [15]

Cereda, E., et al., Current Opinion in Clinical Nutrition & Metabolic Care (2024) 27 (1), 3

2024

[16] [16]

Sadeghi, M., et al., Stem Cell Reviews and Reports (2025), 1

2025

[17] [17]

Xu, X., et al., International journal of biological macromolecules (2023) 235, 123847

2023

[18] [18]

Bombin, A. D. J., et al., Materials Science and Engineering: C (2020) 114, 110994

2020

[19] [19]

Sharifi, M., et al., Journal of Applied Polymer Science (2020) 137 (46), 49528

2020

[20] [20]

Taherinezhad Tayebi, S., et al., International Journal of Polymer Science (2025) 2025 (1), 4149018

2025

[21] [21]

S., et al., International Journal of Biological Macromolecules (2025), 140815

Bajestani, M. S., et al., International Journal of Biological Macromolecules (2025), 140815

2025

[22] [22]

Khatti, T., et al., Neural Computing and Applications (2019) 31, 239

2019

[23] [23]

Fatahian, R., and Erfani, R., Scientific Reports (2025) 15 (1), 12886

2025

[24] [24]

Asadi, N., et al., International journal of biological macromolecules (2021) 193, 734

2021

[25] [25]

Emami, M., et al., Journal of Drug Delivery Science and Technology (2024) 92, 105285

2024

[26] [26]

Kuddushi, M., et al., Advanced Composites and Hybrid Materials (2025) 8 (2), 179

2025

[27] [27]

Sotoudeh, A., et al., European Polymer Journal (2021) 152, 110469

2021

[28] [28]

Firoozi, N., and Kang, Y., Scientific Reports (2020) 10 (1), 10419

2020

[29] [29]

Firoozi, N., and Kang, Y., ACS Biomaterials Science & Engineering (2019) 5 (3), 1257

2019

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Vafa, E., et al., Materials Chemistry and Physics (2024) 316, 129070 42

2024

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Vafa, E., et al., Journal of Materials Research and Technology (2025) 36, 4773

2025

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Jiang, H., et al., Langmuir (2010) 26 (3), 1991

2010

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Ranjbar, S., and Shahrokhian, S., Bioelectrochemistry (2018) 123, 70

2018

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Di Matteo, P., et al., Journal of Composites Science (2025) 9 (1), 25

2025

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Wu, Q., et al., Chemical Engineering Journal (2015) 266, 112

2015

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Bahrami, H., and Sharifi, M., Available at SSRN 5347135

[37] [37]

A., et al., Journal of Polymer Research (2025) 32 (2), 51

Nezhad, P. A., et al., Journal of Polymer Research (2025) 32 (2), 51

2025

[38] [38]

Sharahi, M., et al., Cellulose (2021) 28, 4943

2021

[39] [39]

H., et al., The Journal of the Textile Institute (2024) 115 (10), 1730

Kouchehbaghi, N. H., et al., The Journal of the Textile Institute (2024) 115 (10), 1730

2024

[40] [40]

Haghdoost, F., et al., Journal of Industrial Textiles (2022) 52, 15280837221112406

2022

[41] [41]

Shokrollahi, M., et al., International journal of biological macromolecules (2020) 147, 547

2020

[42] [42]

A., et al., BioNanoScience (2024), 1

Heris, M. A., et al., BioNanoScience (2024), 1

2024

[43] [43]

R., et al., Journal of the Indian Chemical Society (2025), 101691

Kiri, N. R., et al., Journal of the Indian Chemical Society (2025), 101691

2025

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S., et al., Inorganic Chemistry Communications (2022) 139, 109336

Budi, H. S., et al., Inorganic Chemistry Communications (2022) 139, 109336

2022

[45] [45]

Mandegari, M., et al., Fibers and Polymers (2022) 23 (12), 3369

2022

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Arumugam, M., et al., Journal of Drug Delivery Science and Technology (2024) 95, 105620

2024

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Pourhoseyini, T., et al., Polymer Bulletin (2024) 81 (13), 11499

2024

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Karczewski, A., et al., Journal of endodontics (2018) 44 (1), 155

2018