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Accelerated Wound Healing in Minipigs by On-Site Production and Delivery of CXCL12 by Transformed Lactic Acid Bacteria

Non-healing wounds are a growing medical problem and result in considerable suffering. The lack of pharmaceutical treatment options reflects the multistep wound healing process, and the complexity of both translation and assessment of treatment efficacy. We previously demonstrated accelerated healin...

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Detalles Bibliográficos
Autores principales: Öhnstedt, Emelie, Lofton Tomenius, Hava, Frank, Peter, Roos, Stefan, Vågesjö, Evelina, Phillipson, Mia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8876577/
https://www.ncbi.nlm.nih.gov/pubmed/35213962
http://dx.doi.org/10.3390/pharmaceutics14020229
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author Öhnstedt, Emelie
Lofton Tomenius, Hava
Frank, Peter
Roos, Stefan
Vågesjö, Evelina
Phillipson, Mia
author_facet Öhnstedt, Emelie
Lofton Tomenius, Hava
Frank, Peter
Roos, Stefan
Vågesjö, Evelina
Phillipson, Mia
author_sort Öhnstedt, Emelie
collection PubMed
description Non-healing wounds are a growing medical problem and result in considerable suffering. The lack of pharmaceutical treatment options reflects the multistep wound healing process, and the complexity of both translation and assessment of treatment efficacy. We previously demonstrated accelerated healing of full-thickness wounds in mice following topical application of the probiotic bacteria Limosilactobacillus reuteri R2LC transformed to express CXCL12. In this study, safety and biological effects of a freeze-dried formulation of CXCL12-producing L. reuteri (ILP100) were investigated in induced full-thickness wounds in minipigs, and different wound healing evaluation methods (macroscopic, planimetry, 2D-photographs, 3D-scanning, ultrasound) were compared. We found that treatment with ILP100 was safe and accelerated healing, as granulation tissue filled wound cavities 1 day faster in treated compared to untreated/placebo-treated wounds. Furthermore, evaluation using planimetry resulted in 1.5 days faster healing than using 2D photographs of the same wounds, whereas the areas measured using 2D photographs were smaller compared to those obtained from 3D scans accounting for surface curvatures, whereas ultrasound imaging enabled detailed detection of thin epithelial layers. In conclusion, topical administration of the drug candidate ILP100 warrants further clinical development as it was proven to be safe and to accelerate healing using different evaluation methods in minipigs.
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spelling pubmed-88765772022-02-26 Accelerated Wound Healing in Minipigs by On-Site Production and Delivery of CXCL12 by Transformed Lactic Acid Bacteria Öhnstedt, Emelie Lofton Tomenius, Hava Frank, Peter Roos, Stefan Vågesjö, Evelina Phillipson, Mia Pharmaceutics Article Non-healing wounds are a growing medical problem and result in considerable suffering. The lack of pharmaceutical treatment options reflects the multistep wound healing process, and the complexity of both translation and assessment of treatment efficacy. We previously demonstrated accelerated healing of full-thickness wounds in mice following topical application of the probiotic bacteria Limosilactobacillus reuteri R2LC transformed to express CXCL12. In this study, safety and biological effects of a freeze-dried formulation of CXCL12-producing L. reuteri (ILP100) were investigated in induced full-thickness wounds in minipigs, and different wound healing evaluation methods (macroscopic, planimetry, 2D-photographs, 3D-scanning, ultrasound) were compared. We found that treatment with ILP100 was safe and accelerated healing, as granulation tissue filled wound cavities 1 day faster in treated compared to untreated/placebo-treated wounds. Furthermore, evaluation using planimetry resulted in 1.5 days faster healing than using 2D photographs of the same wounds, whereas the areas measured using 2D photographs were smaller compared to those obtained from 3D scans accounting for surface curvatures, whereas ultrasound imaging enabled detailed detection of thin epithelial layers. In conclusion, topical administration of the drug candidate ILP100 warrants further clinical development as it was proven to be safe and to accelerate healing using different evaluation methods in minipigs. MDPI 2022-01-19 /pmc/articles/PMC8876577/ /pubmed/35213962 http://dx.doi.org/10.3390/pharmaceutics14020229 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Öhnstedt, Emelie
Lofton Tomenius, Hava
Frank, Peter
Roos, Stefan
Vågesjö, Evelina
Phillipson, Mia
Accelerated Wound Healing in Minipigs by On-Site Production and Delivery of CXCL12 by Transformed Lactic Acid Bacteria
title Accelerated Wound Healing in Minipigs by On-Site Production and Delivery of CXCL12 by Transformed Lactic Acid Bacteria
title_full Accelerated Wound Healing in Minipigs by On-Site Production and Delivery of CXCL12 by Transformed Lactic Acid Bacteria
title_fullStr Accelerated Wound Healing in Minipigs by On-Site Production and Delivery of CXCL12 by Transformed Lactic Acid Bacteria
title_full_unstemmed Accelerated Wound Healing in Minipigs by On-Site Production and Delivery of CXCL12 by Transformed Lactic Acid Bacteria
title_short Accelerated Wound Healing in Minipigs by On-Site Production and Delivery of CXCL12 by Transformed Lactic Acid Bacteria
title_sort accelerated wound healing in minipigs by on-site production and delivery of cxcl12 by transformed lactic acid bacteria
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8876577/
https://www.ncbi.nlm.nih.gov/pubmed/35213962
http://dx.doi.org/10.3390/pharmaceutics14020229
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