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Cited by 1Traumatic Brain Injury and Neurovascular DisturbancesAdvanced Drug Delivery SystemsTraumatic Brain Injury Research

The DOI matches its Crossref record; 65 of the 65 references it cites were found in a registry or an index; none of the 39 sources its claims cite is checked for support yet.

Realization of differential release of minocycline hydrochloride from electrosprayed polymeric or biomacromolecular microparticles for the repair of traumatic brain injury

Open access
Guo, Qingxia, Wang, Yue, Fu, Manfei, Zhou, Ziyi, Zhang, Xiaopei, Chen, Siyu, Xu, Cong, Wang, Yuanfei, Wu, Tong·2025·Materials Today Bio
DOI 10.1016/j.mtbio.2025.102309PMC PMC12478139
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Abstract

experiments further proved that MH@SF and MH@PLGA microparticles alleviate the neuroinflammation microenvironment and enhance motor, learning, and memory functions of mice after TBI. In summary, this work proposed a promising strategy to regulate the neuroimmune microenvironment through matching different pathophysiological stages of TBI, demonstrating potential for clinical translation to treat TBI.

Overview

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TL;DR

Coaxial electrosprayed core-shell microparticles loading minocycline hydrochloride (MH) in silk fibroin (SF) or PLGA shells achieved differential release—fast over 7 days for SF and sustained up to 25 days for PLGA. In TBI models, these microparticles reduced neuroinflammation, promoted M2 microglial polarization, enhanced neuronal viability/neurite growth, and improved motor and cognitive recovery, though clinical validation remains.

Key findings

  • MH@PLGA and MH@SF microparticles had average diameters of 1.38 ± 0.26 μm and 2.74 ± 0.78 μm, with MH loading efficiencies of 71.84% and 79.16%, respectively. In the first 24 h, 51.97% (PLGA) and 61.63% (SF) of MH was released; SF gave rapid release over 7 days, while PLGA sustained release up to 25 days.
  • In LPS-stimulated BV2 cells, NO release increased to 1.39 μM versus 0.53 μM in controls, while +MH groups were all below 0.5 μM (P < 0.05). MH-loaded microparticles lowered IL-1β/TNF-α and iNOS, and increased IL-4/IL-10 and Arg-1, supporting M2 polarization.
  • After neurite transection (NT), average neurite length was 36.43 ± 14.13 μm in LPS versus 49.95 ± 20.34 μm in controls; MH@PLGA and MH@SF increased it to 59.93 ± 28.65 μm and 63.16 ± 19.26 μm. After oxygen-glucose deprivation (OGD), average neurite length was 18.57 ± 16.50 μm in LPS versus 30.85 ± 16.77 μm in controls; MH@PLGA and MH@SF reached 34.72 ± 21.64 μm and 35.45 ± 23.98 μm, with higher viability.
  • In moderate TBI mice, mNSS scores were significantly lower in MH@SF and MH@PLGA groups on days 10 and 14. On day 12, escape latency was reduced to 25.09 s and 14.90 s in MH-loaded groups versus 53.16 s in controls; target-quadrant time was 47.4% (MH@SF) and 40.6% (MH@PLGA) versus 33.2% control and 32.2% sham. MH-loaded microparticles reduced serum IL-6/IL-1β, increased IL-4, and showed no pathological organ changes at 28 days.

Methods

  • Core-shell microparticles were fabricated by coaxial electrospray with MH as the core and PLGA or SF as the shell, then characterized by SEM, fluorescence imaging, FTIR, and in vitro release in PBS.
  • In vitro studies used BV2 microglia with LPS, primary rat cortical neurons, and SH-SY5Y cells in NT and OGD models; outcomes included CCK-8 viability, NO/ELISA, Western blot, and immunofluorescence for iNOS, Arg-1, MAP-2, SYP, and NeuN.
  • In vivo, 72 male C57BL/6 mice received Feeney free-fall moderate TBI and were randomized to MH@SF, MH@PLGA, SF, PLGA, control, or sham groups; assessments included mNSS, Morris water maze, ELISA, immunofluorescence, HE staining, and Nissl staining, with one-way ANOVA and Student’s t-test.

Limitations

  • The paper states that although the microparticles are promising clinical candidates, their therapeutic effects need to be verified by clinical trials.
  • Evident from the text: in vivo experiments used only male C57BL/6 mice and a single moderate TBI model, so sex- and model-related generalizability is not established.
  • Evident from the text: organ safety histology was assessed at 28 days; longer-term degradation, toxicity, and human translation were not evaluated.

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Registry

Crossref · 10.1016/j.mtbio.2025.102309

Cites

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Statistics

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Figures

Graphical abstract Graphical abstract MH@PLGA microparticles and MH@SF microparticles were prepared through coaxial electrospray. The optimal release time window for MH was determined by optimizing the preparation parameters to enhance nerve repair after TBI. The effects of MH@PLGA and MH@SF microparticles include inflammation inhibition, followed by the promotion of neuron production, leading to significant recovery of motor, learning, and memory functions in a moderate TBI mouse model.
Graphical abstract Graphical abstract MH@PLGA microparticles and MH@SF microparticles were prepared through coaxial electrospray. The optimal release time window for MH was determined by optimizing the preparation parameters to enhance nerve repair after TBI. The effects of MH@PLGA and MH@SF microparticles include inflammation inhibition, followed by the promotion of neuron production, leading to significant recovery of motor, learning, and memory functions in a moderate TBI mouse model.CC BY-NC · PubMed Central
Fig. 1 Schematic illustration, characterization, and release behaviors. (A) Schematic illustration of core-shell microparticles (MH@PLGA and MH@SF) prepared by coaxial electrospaying. (B) SEM images of MH@PLGA microparticles and MH@SF microparticles. The enlarged images are in the upper right, the scale bar = 1 μm. (C–E) Fluorescence micrographs showing the structure of microparticles, BSA/FITC was loaded in the core layer (green), the enlarged images are in the upper right, the scale bar = 5 μm. (F) FTIR spectra of MH, PLGA, SF, MH@PLGA microparticles, and MH@SF microparticles. (G) Release profiles of MH from MH@PLGA microparticles. (H) Release profiles of MH from MH@SF microparticles. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)
Fig. 1 Schematic illustration, characterization, and release behaviors. (A) Schematic illustration of core-shell microparticles (MH@PLGA and MH@SF) prepared by coaxial electrospaying. (B) SEM images of MH@PLGA microparticles and MH@SF microparticles. The enlarged images are in the upper right, the scale bar = 1 μm. (C–E) Fluorescence micrographs showing the structure of microparticles, BSA/FITC was loaded in the core layer (green), the enlarged images are in the upper right, the scale bar = 5 μm. (F) FTIR spectra of MH, PLGA, SF, MH@PLGA microparticles, and MH@SF microparticles. (G) Release profiles of MH from MH@PLGA microparticles. (H) Release profiles of MH from MH@SF microparticles. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)CC BY-NC · PubMed Central
Fig. 2 Effects of microparticles on the viability and phenotype of BV2 cells. (A) Cell viability of BV2 cells (mean ± SD, n = 3, ∗P < 0.05, ∗∗P < 0.01 compared to the control group). (B) NO release from the supernatant of BV2 cell culture (mean ± SD, n = 3, ∗P < 0.05, ∗∗P < 0.01 compared to the control group. #P < 0.05, ##P < 0.01, ###P < 0.001 compared to the LPS group). (C–F) ELISA analysis of IL-1β, TNF-α, IL-4 and IL-10 from the supernatant of BV2 cell culture (mean ± SD, n = 3, ∗P < 0.05, ∗∗P < 0.01 compared with the control group. #P < 0.05, ##P < 0.01, ###P < 0.001 compared to the LPS group). (G) Western blot analysis of iNOS (M1) and Arg-1 (M2) protein levels in BV2 cells across different groups. (H) Immunofluorescence staining for iNOS (red) and Arg-1 (green) was utilized to characterize BV2 cell polarization across various groups. The nuclei were stained blue. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)
Fig. 2 Effects of microparticles on the viability and phenotype of BV2 cells. (A) Cell viability of BV2 cells (mean ± SD, n = 3, ∗P < 0.05, ∗∗P < 0.01 compared to the control group). (B) NO release from the supernatant of BV2 cell culture (mean ± SD, n = 3, ∗P < 0.05, ∗∗P < 0.01 compared to the control group. #P < 0.05, ##P < 0.01, ###P < 0.001 compared to the LPS group). (C–F) ELISA analysis of IL-1β, TNF-α, IL-4 and IL-10 from the supernatant of BV2 cell culture (mean ± SD, n = 3, ∗P < 0.05, ∗∗P < 0.01 compared with the control group. #P < 0.05, ##P < 0.01, ###P < 0.001 compared to the LPS group). (G) Western blot analysis of iNOS (M1) and Arg-1 (M2) protein levels in BV2 cells across different groups. (H) Immunofluorescence staining for iNOS (red) and Arg-1 (green) was utilized to characterize BV2 cell polarization across various groups. The nuclei were stained blue. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)CC BY-NC · PubMed Central
Fig. 3 The impact of BV2 cell polarization on the viability, neurite length, and number of primary neurons after NT and OGD treatments. (A) After NT treatment, the viability of primary neurons (mean ± SD, n = 3, ∗P < 0.05, ∗∗P < 0.01 compared to the control group, #P < 0.05, ##P < 0.01, ###P < 0.001 compared to the LPS group). (B) After NT treatment, the immunofluorescence images of primary neurons. DAPI (blue), SYP (green), MAP2 (red), and merged illustration. (C) After OGD treatment, the viability of primary neurons (mean ± SD, n = 3, ∗P < 0.05, ∗∗P < 0.01 compared to the control group, #P < 0.05, ##P < 0.01, ###P < 0.001 compared to the LPS group). (D) After OGD treatment, the immunofluorescence images of primary neurons. DAPI (blue), SYP (green), MAP2 (red), and merged illustration. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)
Fig. 3 The impact of BV2 cell polarization on the viability, neurite length, and number of primary neurons after NT and OGD treatments. (A) After NT treatment, the viability of primary neurons (mean ± SD, n = 3, ∗P < 0.05, ∗∗P < 0.01 compared to the control group, #P < 0.05, ##P < 0.01, ###P < 0.001 compared to the LPS group). (B) After NT treatment, the immunofluorescence images of primary neurons. DAPI (blue), SYP (green), MAP2 (red), and merged illustration. (C) After OGD treatment, the viability of primary neurons (mean ± SD, n = 3, ∗P < 0.05, ∗∗P < 0.01 compared to the control group, #P < 0.05, ##P < 0.01, ###P < 0.001 compared to the LPS group). (D) After OGD treatment, the immunofluorescence images of primary neurons. DAPI (blue), SYP (green), MAP2 (red), and merged illustration. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)CC BY-NC · PubMed Central
Fig. 4 In vivo recovery assessment of each group. (A) Timeline of in vivo experiments. (B) Experimental procedure for establishing the TBI model. (C) The mNSS test evaluates the motor abilities and mNSS scores of mice at different points in time (mean ± SD, n = 8). (D) Escape latency in mice from day 7 to day 11 after treatment (mean ± SD, n = 8). (E) The timeline of the MWM test. (F) Escape latency of mice on day12 after treatment (mean ± SD, n = 8, ∗P < 0.05, ∗∗P < 0.01 compared to the MH@PLGA group. #P < 0.05, ##P < 0.01, ###P < 0.001 compared to the MH@SF group). (G) Time in novel arm of mice at day 12 after treatment (mean ± SD, n = 8, ∗P < 0.05, ∗∗P < 0.01 compared to the MH@PLGA group. #P < 0.05, ##P < 0.01, ###P < 0.001 compared to the MH@SF group). (H) Representative movement tracks on day 12. (I–K) The expression of inflammatory factors (IL-6, IL-1β, and IL-4) in the serum of mice after 14 days following the injury. (mean ± SD, n = 3, ∗P < 0.05, ∗∗P < 0.01 compared to the MH@PLGA group. #P < 0.05, ##P < 0.01, ###P < 0.001 compared to the MH@SF group).
Fig. 4 In vivo recovery assessment of each group. (A) Timeline of in vivo experiments. (B) Experimental procedure for establishing the TBI model. (C) The mNSS test evaluates the motor abilities and mNSS scores of mice at different points in time (mean ± SD, n = 8). (D) Escape latency in mice from day 7 to day 11 after treatment (mean ± SD, n = 8). (E) The timeline of the MWM test. (F) Escape latency of mice on day12 after treatment (mean ± SD, n = 8, ∗P < 0.05, ∗∗P < 0.01 compared to the MH@PLGA group. #P < 0.05, ##P < 0.01, ###P < 0.001 compared to the MH@SF group). (G) Time in novel arm of mice at day 12 after treatment (mean ± SD, n = 8, ∗P < 0.05, ∗∗P < 0.01 compared to the MH@PLGA group. #P < 0.05, ##P < 0.01, ###P < 0.001 compared to the MH@SF group). (H) Representative movement tracks on day 12. (I–K) The expression of inflammatory factors (IL-6, IL-1β, and IL-4) in the serum of mice after 14 days following the injury. (mean ± SD, n = 3, ∗P < 0.05, ∗∗P < 0.01 compared to the MH@PLGA group. #P < 0.05, ##P < 0.01, ###P < 0.001 compared to the MH@SF group).CC BY-NC · PubMed Central
Fig. 5 MH-loaded microparticles inhibited inflammation following TBI. (A) Immunofluorescence staining of Arg-1 (green) and DAPI (blue), along with a merged illustration, in the damaged brain tissues at 14 days post-injury. (B) Immunofluorescence staining of iNOS (red), DAPI (blue), and a merged illustration in the damaged brain tissues at 14 days post-injury. (C) Fluorescence micrographs of mature neurons in the DG region, with NeuN (green), DAPI (blue), and a merged illustration at 14 days post-injury. (D–F) Quantification of fluorescence intensity of Arg-1, iNOS and NeuN (mean ± SD, n = 3, ∗P < 0.05, ∗∗P < 0.01 compared to the MH@PLGA group. #P < 0.05, ##P < 0.01, ###P < 0.001 compared to the MH@SF group). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)
Fig. 5 MH-loaded microparticles inhibited inflammation following TBI. (A) Immunofluorescence staining of Arg-1 (green) and DAPI (blue), along with a merged illustration, in the damaged brain tissues at 14 days post-injury. (B) Immunofluorescence staining of iNOS (red), DAPI (blue), and a merged illustration in the damaged brain tissues at 14 days post-injury. (C) Fluorescence micrographs of mature neurons in the DG region, with NeuN (green), DAPI (blue), and a merged illustration at 14 days post-injury. (D–F) Quantification of fluorescence intensity of Arg-1, iNOS and NeuN (mean ± SD, n = 3, ∗P < 0.05, ∗∗P < 0.01 compared to the MH@PLGA group. #P < 0.05, ##P < 0.01, ###P < 0.001 compared to the MH@SF group). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)CC BY-NC · PubMed Central
Fig. 6 MH-loaded microparticles reduced tissue loss and promoted neuronal regeneration following TBI. (A) Representative photographs of injured brains. (B) HE staining of tissue sections. (C) Nissl staining of tissue sections. (D) Quantitative analysis of lesion volume in each group after 14 days of treatment (mean ± SD, n = 3, ∗P < 0.05, ∗∗P < 0.01 compared to the MH@PLGA group. #P < 0.05, ##P < 0.01, ###P < 0.001 compared to the MH@SF group). (E) Quantitative analysis of the number of Nissl bodies in each group after 14 days of treatment (mean ± SD, n = 3, ∗P < 0.05, ∗∗P < 0.01 compared to the MH@PLGA group. #P < 0.05, ##P < 0.01, ###P < 0.001 compared to the MH@SF group).
Fig. 6 MH-loaded microparticles reduced tissue loss and promoted neuronal regeneration following TBI. (A) Representative photographs of injured brains. (B) HE staining of tissue sections. (C) Nissl staining of tissue sections. (D) Quantitative analysis of lesion volume in each group after 14 days of treatment (mean ± SD, n = 3, ∗P < 0.05, ∗∗P < 0.01 compared to the MH@PLGA group. #P < 0.05, ##P < 0.01, ###P < 0.001 compared to the MH@SF group). (E) Quantitative analysis of the number of Nissl bodies in each group after 14 days of treatment (mean ± SD, n = 3, ∗P < 0.05, ∗∗P < 0.01 compared to the MH@PLGA group. #P < 0.05, ##P < 0.01, ###P < 0.001 compared to the MH@SF group).CC BY-NC · PubMed Central

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  1. Liu, 2024, Gradient galectin-1 coating technology: bionic multichannel nerve guidance conduits promote neural cell migration, Adv Technol Neurosci, 1, 276
  2. Badenes, 2024, Epidermal growth factor receptor pathway in central nervous system regenerative medicine: a narrative review, Regen Med Rep, 1, 172

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Metadata

Authors
Guo, Q., Wang, Y., Fu, M., Zhou, Z., Zhang, X., Chen, S., Xu, C., Wang, Y., & Wu, T.
Affiliations
  • Qingdao University (CN)
  • Army Medical University (CN)
Corresponding author
Wu, Tong
ORCID
Venue
Materials Today Bio
Publisher
Elsevier BV
Published
2025-12
Volume
35
Pages
102309
ISSN
2590-0064 (ISSN-L)
DOI
10.1016/j.mtbio.2025.102309
PMC
PMC12478139
OpenAlex
W4414751317
Semantic Scholar
af983c0107f11c4f85f02ccc70a5947c523541f7
Cited by
1
References
65
Citations by year
2026: 1
FWCI
0.50
Type
journal article
Language
en
Open access
Licence
Locations
  • Materials Today Bio (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Taishan Scholar Foundation of Shandong Province
  • National Natural Science Foundation of China (32171322)
  • Shandong Province Natural Science Foundation (ZR2024JQ026)
Topics
  • Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
Keywords
minocycline hydrochloride, traumatic brain injury, electrospraying, polymeric microparticles, sustained drug release, neuroinflammation, PLGA, silk fibroin

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CoChat. (2026). Citation check: Realization of differential release of minocycline hydrochloride from electrosprayed polymeric or biomacromolecular microparticles for the repair of traumatic brain injury. https://app.cochat.ai/papers/10.1016/j.mtbio.2025.102309
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Guo, Q., Wang, Y., Fu, M., Zhou, Z., Zhang, X., Chen, S., Xu, C., Wang, Y., & Wu, T. (2025). Realization of differential release of minocycline hydrochloride from electrosprayed polymeric or biomacromolecular microparticles for the repair of traumatic brain injury. Materials Today Bio. https://doi.org/10.1016/j.mtbio.2025.102309

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