Fabrication and characterization of bioprints with Lactobacillus crispatus for vaginal application.
3D bioprinting
Bacterial vaginosis
Female reproductive tract
Lactobacillus crispatus
Probiotics
women's health
Journal
Journal of controlled release : official journal of the Controlled Release Society
ISSN: 1873-4995
Titre abrégé: J Control Release
Pays: Netherlands
ID NLM: 8607908
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
received:
28
10
2022
revised:
06
04
2023
accepted:
13
04
2023
pmc-release:
01
05
2024
medline:
9
5
2023
pubmed:
20
4
2023
entrez:
19
04
2023
Statut:
ppublish
Résumé
Bacterial vaginosis (BV) is characterized by low levels of lactobacilli and overgrowth of potential pathogens in the female genital tract. Current antibiotic treatments often fail to treat BV in a sustained manner, and > 50% of women experience recurrence within 6 months post-treatment. Recently, lactobacilli have shown promise for acting as probiotics by offering health benefits in BV. However, as with other active agents, probiotics often require intensive administration schedules incurring difficult user adherence. Three-dimensional (3D)-bioprinting enables fabrication of well-defined architectures with tunable release of active agents, including live mammalian cells, offering the potential for long-acting probiotic delivery. One promising bioink, gelatin alginate has been previously shown to provide structural stability, host compatibility, viable probiotic incorporation, and cellular nutrient diffusion. This study formulates and characterizes 3D-bioprinted Lactobacillus crispatus-containing gelatin alginate scaffolds for gynecologic applications. Different weight to volume (w/v) ratios of gelatin alginate were bioprinted to determine formulations with highest printing resolution, and different crosslinking reagents were evaluated for effect on scaffold integrity via mass loss and swelling measurements. Post-print viability, sustained-release, and vaginal keratinocyte cytotoxicity assays were conducted. A 10:2 (w/v) gelatin alginate formulation was selected based on line continuity and resolution, while degradation and swelling experiments demonstrated greatest structural stability with dual genipin and calcium crosslinking, showing minimal mass loss and swelling over 28 days. 3D-bioprinted L. crispatus-containing scaffolds demonstrated sustained release and proliferation of live bacteria over 28 days, without impacting viability of vaginal epithelial cells. This study provides in vitro evidence for 3D-bioprinted scaffolds as a novel strategy to sustain probiotic delivery with the ultimate goal of restoring vaginal lactobacilli following microbiological disturbances.
Identifiants
pubmed: 37076014
pii: S0168-3659(23)00273-0
doi: 10.1016/j.jconrel.2023.04.023
pmc: PMC10696519
mid: NIHMS1948405
pii:
doi:
Substances chimiques
Gelatin
9000-70-8
Alginates
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
545-560Subventions
Organisme : NIAID NIH HHS
ID : R01 AI168475
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier B.V. All rights reserved.
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