Mannose-Decorated Co-Polymer Facilitates Controlled Release of Butyrate to Accelerate Chronic Wound Healing

Butyrate is a key bacterial metabolite that plays an important and complex role in modulation of immunity and maintenance of epithelial barriers. Its translation to clinic is limited by poor bioavailability, pungent smell, and the need for high doses, and effective delivery strategies have yet to re...

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Bibliographic Details
Published in:Advanced healthcare materials 2023-10, Vol.12 (26), p.e2300515
Main Authors: Lauterbach, Abigail L, Slezak, Anna J, Wang, Ruyi, Cao, Shijie, Raczy, Michal M, Watkins, Elyse A, Jimenez, Carlos J Medina, Hubbell, Jeffrey A
Format: Article
Language:English
Subjects:
Bioavailability
Butyrates - pharmacology
Butyrates - therapeutic use
Cell activation
Chemokines
Controlled release
Delayed-Action Preparations - pharmacology
Diabetes
Diabetes mellitus
Diabetes Mellitus - drug therapy
Effectiveness
Esters
Humans
Immune system
Mannose
Metabolites
Methacrylamide
Microenvironments
Modulation
Polymers - pharmacology
Wound Healing
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Summary:Butyrate is a key bacterial metabolite that plays an important and complex role in modulation of immunity and maintenance of epithelial barriers. Its translation to clinic is limited by poor bioavailability, pungent smell, and the need for high doses, and effective delivery strategies have yet to realize clinical potential. Here, a novel polymeric delivery platform for tunable and sustainable release of butyrate consisting of a methacrylamide backbone with butyryl ester or phenyl ester side chains as well as mannosyl side chains, which is also applicable to other therapeutically relevant metabolites is reported. This platform's utility in the treatment of non-healing diabetic wounds is explored. This butyrate-containing material modulated immune cell activation in vitro and induced striking changes in the milieu of soluble cytokine and chemokine signals present within the diabetic wound microenvironment in vivo. This novel therapy shows efficacy in the treatment of non-healing wounds through the modulation of the soluble signals present within the wound, and importantly accommodates the critical temporal regulation associated with the wound healing process. Currently, the few therapies to address non-healing wounds demonstrate limited efficacy. This novel platform is positioned to address this large unmet clinical need and improve the closure of otherwise non-healing wounds.
ISSN:2192-2640
2192-2659
2192-2659
DOI:10.1002/adhm.202300515