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Minocycline-loaded PLGA electrospun membrane prevents alveolar bone loss in experimental peridontitis
Open accessAbstract
Minocycline (MINO) is a tetracycline antibiotic effective against most of the bacteria microorganisms related to periodontal disease. Additionally, MINO promotes bone in vitro and in vivo. The objective of the present study was to establish the protocol for the preparation of MINO-loaded poly (lactic-co-glycolic acid) (MINO-PLGA) electrospun membranes and to evaluate their effect on osteogenesis in vitro and in a rat model of periodontitis. The characterization of MINO-PLGA electrospun membranes was assessed by scanning electron microscopy, laser scanning confocal microscopy, and contact angle measurement. The drug release study showed a sustained diffusion of MINO from electrospun membranes over a period of 40 d. The MINO-PLGA membranes containing 2% of the drug exhibited better support of osteoblast proliferation and adhesion and was subsequently used in vivo in an experimental periodontitis model. Its therapeutic potential was evaluated by the measurement of alveolar bone loss (ABL), bone volume analysis, histological analysis, and immunohistochemistry. MINO-PLGA membrane increased alveolar crest height in the periodontitis model, inhibited the expression of the ligand of the receptor activator for nuclear factor-κB (RANKL), and promoted the expression of its inhibitor, osteoprotegerin. The study demonstrated that MINO-PLGA electrospun membranes may be applied to stimulate bone regeneration in periodontitis.
Overview
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TL;DR
Minocycline-loaded PLGA electrospun membranes released MINO over 40 days and, especially at 2% MINO, supported osteoblast attachment and proliferation in vitro. In a ligature-induced rat periodontitis model, 2% MINO-PLGA increased alveolar bone parameters, reduced alveolar bone loss, decreased RANKL, and increased OPG compared with ligation/PLGA controls.
Key findings
- MINO-PLGA fibers were ribbon-shaped with average diameters of 1661, 1618, 1579, and 1569 nm for 0%, 1%, 2%, and 3% MINO, respectively (p > .05); contact angles decreased significantly with MINO loading (86.970° ± 3.698°, 74.354° ± 6.917°, 73.686° ± 9.642°, 68.684° ± 12.580°; p < .05).
- Release showed an initial burst on day 1 (21.11%, 23.17%, and 28.06% for 1%, 2%, and 3% MINO-PLGA) and sustained release over 40 d (76.33%, 81.26%, and 87.42%, respectively); the Ritger–Peppas model fit best (R² > 0.990), and residual membrane weight was approximately 52% at 60 d.
- From day 3, osteoblast proliferation was significantly higher on MINO-PLGA membranes, particularly 2% MINO-PLGA, compared with PLGA (p < .05); SEM showed cells attached via filopodia.
- In vivo, ABL at 3 weeks was 1.02 ± 0.084 mm (MINO-PLGA), 1.06 ± 0.076 mm (Periocline®), 1.23 ± 0.049 mm (ligation), and 1.20 ± 0.046 mm (PLGA); at 6 weeks it was 0.73 ± 0.055 mm, 0.84 ± 0.111 mm, 1.05 ± 0.097 mm, and 1.03 ± 0.114 mm, respectively. MINO-PLGA and Periocline® prevented ligature-induced BV/TV decreases versus ligation and PLGA (p < .05), and IHC showed decreased RANKL and increased OPG.
Methods
- PLGA (LA:GA = 50:50, MW = 70,000) was dissolved in chloroform; MINO was added at 1, 2, or 3 wt%, and membranes were electrospun at 15 kV, 18 cm distance, and 3 mL/h. Characterization included SEM, FTIR, laser scanning confocal microscopy, and contact angle measurement.
- In vitro, MINO release was measured in PBS at 37 °C by absorbance at 375 nm over 40 d; degradation was measured by weight loss. Osteoblasts from newborn Sprague–Dawley rat cranial bones were used for CCK-8 proliferation and SEM attachment assays.
- In vivo, female Sprague–Dawley rats (7 weeks old) were randomized to five groups (n = 5 each): control, ligation, ligation + PLGA, ligation + 2% MINO-PLGA, and ligation + Periocline®. After 4 weeks of ligature-induced periodontitis, treatments were applied, and micro-CT, H&E histology, and immunohistochemistry for OPG/RANKL were assessed at 3 and 6 weeks; one-way ANOVA and SNK-q tests were used with p < .05.
Limitations
- Paper-stated: co-electrospinning MINO with PLGA could not completely prevent the initial burst release, and the authors state that a better drug-loading method will be explored in future research to further reduce burst release.
- Evident from the text: in vivo testing used only the 2% MINO-PLGA formulation, so no in vivo dose–response across 1%, 2%, and 3% MINO is established.
- Evident from the text: antimicrobial efficacy was not directly assessed despite the antibiotic rationale, and several in vivo/assay groups used small sample sizes (n = 5 in vivo; n = 3 for some in vitro and IHC analyses).
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0 Valid · 0 Not valid · 35 Not checked · 57 Own results and interpretations
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of note, the amount of MINO released from the electrospun membranes increased with higher concentrations (p < .05).”
§ Minocycline-loaded PLGA electrospun membrane prevents alveolar bone loss in experimental peridontitis > Results > In vitro release and degradation of MINO-PLGA
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The difference in ABL between MINO-PLGA and Periocline® treatments were statistically significant at 6 weeks (p < .05).”
§ Minocycline-loaded PLGA electrospun membrane prevents alveolar bone loss in experimental peridontitis > Results > In vivo studies
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, the quantification of bone parameters demonstrated that MINO-PLGA and Periocline® treatment significantly prevented the ligature-induced decreases in BV/TV when compared with the ligation and ligation + PLGA groups at 3 and 6 weeks (p < .05; Figure 4(A)).”
§ Minocycline-loaded PLGA electrospun membrane prevents alveolar bone loss in experimental peridontitis > Results > In vivo studies
boostedstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and 0.73 ± 0.055 mm, 0.84 ± 0.111 mm, 1.05 ± 0.097 mm, and 1.03 ± 0.114 mm at 6 weeks.”
§ Minocycline-loaded PLGA electrospun membrane prevents alveolar bone loss in experimental peridontitis > Results > In vivo studies
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“On day 1, there was no statistically significant difference among the four groups (p > .05).”
§ Minocycline-loaded PLGA electrospun membrane prevents alveolar bone loss in experimental peridontitis > Results > Cell attachment and proliferation
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Both in‐development minocycline formulations and clinically utilized medications currently necessitate specialized delivery devices for administration into periodontal pockets.”
From Facile minocycline deployment in gingiva using a dissolvable microneedle patch for the adjunctive treatment of periodontal disease (2025) · cites this paper as [27]
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Percentages, sums and reported differences re-computed from the paper’s own numbers.
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Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ Minocycline-loaded PLGA electrospun membrane prevents alveolar bone loss in experimental peridontitis > Materials and methods > Animals and experimental design for the induction of periodontitis
“female Sprague–Dawley rats (7 weeks old) from the Institute of Experimental Animal Center of Chongqing Medical University were assigned randomly to five groups, with 5 rats in each group”
§ Minocycline-loaded PLGA electrospun membrane prevents alveolar bone loss in experimental peridontitis > Materials and methods > Animals and experimental design for the induction of periodontitis
“(3 weeks and 6 weeks, n = 5 at each time point).”
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ Minocycline-loaded PLGA electrospun membrane prevents alveolar bone loss in experimental peridontitis > Materials and methods > Animals and experimental design for the induction of periodontitis
“an orthodontic steel wire (0.2 mm in diameter) was ligated around the cervix of the mandibular first molars for 4 weeks”
§ Minocycline-loaded PLGA electrospun membrane prevents alveolar bone loss in experimental peridontitis > Materials and methods > Animals and experimental design for the induction of periodontitis
“The linear distance of ABL was measured from the cementoenamel junction (CEJ) to the alveolar bone crest (ABC) at the distal and mesial root of the upper first molar”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Minocycline-loaded PLGA electrospun membrane prevents alveolar bone loss in experimental peridontitis > Materials and methods > Animals and experimental design for the induction of periodontitis
“This procedure was not performed in the control group.”
§ Minocycline-loaded PLGA electrospun membrane prevents alveolar bone loss in experimental peridontitis > Materials and methods > Animals and experimental design for the induction of periodontitis
“After the periodontitis model was established, the ligatures were removed, and the periodontal pockets were left without treatment (control group)”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Minocycline-loaded PLGA electrospun membrane prevents alveolar bone loss in experimental peridontitis > Results > In vivo studies
“p < .05; Figure 4(A)). The alveolar bone loss (ABL) was assessed using the images of 2 D micro-CT sections (Figure 4(B)).”
§ Minocycline-loaded PLGA electrospun membrane prevents alveolar bone loss in experimental peridontitis > Results > In vivo studies
“Figure: Figure 4. (A) The degree of alveolar bone loss was evaluated by measuring the CEJ-ABC distance at the distal and mesial root of the first molar from the reconstructed micro-CT images, (B) analysis of micro-CT volumetric parameters: bone volume/tissue volume (BV/TV).”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Minocycline-loaded PLGA electrospun membrane prevents alveolar bone loss in experimental peridontitis > Materials and methods > Animals and experimental design for the induction of periodontitis
“The expression of the osteogenic marker osteogenic growth peptide (OPG) and the osteoclastic marker RANK ligand (RANKL) was evaluated at 3 and 6 weeks after ligation.”
§ Minocycline-loaded PLGA electrospun membrane prevents alveolar bone loss in experimental peridontitis > Abstract
“promoted the expression of its inhibitor, osteoprotegerin.”
Citations
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Cited by
Recent advances in PLGA-based biomaterials for bone tissue regeneration
Jin, S., Xia, X., Huang, J., Yuan, C., Zuo, Y., Li, Y., & Li, J. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.03.067 · Cited by 295
Functional biomaterials for comprehensive periodontitis therapy
Luan, J., Li, R., Xu, W., Sun, H., Li, Q., Wang, D., Dong, S., & Ding, J. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.10.026 · Cited by 144
Martins, A. M., Marto, J. M., Johnson, J. L., & Graber, E. (2021) · Antibiotics · doi:10.3390/antibiotics10070757 · Cited by 115
Electrospun trilayer eccentric Janus nanofibers for a combined treatment of periodontitis
Zhao, P., Zhou, K., Xia, Y., Qian, C., Yu, D., Xie, Y., & Liao, Y. (2024) · Advanced Fiber Materials · doi:10.1007/s42765-024-00397-6 · Cited by 109
Electrospun Nanofibers for Periodontal Treatment: A Recent Progress
Zhao, P., Chen, W., Feng, Z., Liu, Y., Liu, P., Xie, Y., & Yu, D. (2022) · International Journal of Nanomedicine · doi:10.2147/ijn.s370340 · Cited by 103
Metadata
- Authors
- Ma, Y., Song, J., Almassri, H. N. S., Zhang, D., Zhang, T., Cheng, Y., & Wu, X.
- Affiliations
- Stomatological Hospital of Chongqing Medical University (CN)
- Stomatological Hospital of Chongqing Medical University, Yubei District, Chongqing, China
- Corresponding author
- Wu, Xiaohong
- Venue
- Drug Delivery
- Publisher
- Informa UK Limited
- Published
- 2020-01
- Volume
- 27
- Issue
- 1
- Pages
- 151-160
- ISSN
- 1071-7544 (ISSN-L)
- 1521-0464
- PMC
- PMC6968699
- OpenAlex
- W3000048516
- Cited by
- 51
- References
- 43
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 13 · 2023: 8 · 2022: 5 · 2021: 10 · 2020: 6
- FWCI
- 1.76
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Drug Delivery (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (81970914, 81570981)
- Chongqing Yuzhong Science and Technology Project (20170117)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Electrospun Nanofibers in Biomedical Applications
- Health Sciences › Dentistry › Periodontics › Periodontal Regeneration and Treatments
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- minocycline, PLGA, electrospun membranes, periodontitis, alveolar bone loss, bone formation, osteoblast proliferation, sustained drug release, RANKL, osteoprotegerin, bone regeneration, tetracycline antibiotics
- MeSH terms
- Animals, Bone Regeneration, Cells, Cultured, Minocycline, Osteoblasts, Osteogenesis, Polyglycolic Acid, Alveolar Bone Loss, Rats, Tissue Scaffolds, Drug Liberation
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- CoChat. (2026). Citation check: Minocycline-loaded PLGA electrospun membrane prevents alveolar bone loss in experimental peridontitis. https://app.cochat.ai/papers/10.1080/10717544.2019.1709921
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- Ma, Y., Song, J., Almassri, H. N. S., Zhang, D., Zhang, T., Cheng, Y., & Wu, X. (2020). Minocycline-loaded PLGA electrospun membrane prevents alveolar bone loss in experimental peridontitis. Drug Delivery. https://doi.org/10.1080/10717544.2019.1709921
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