Controlled and Local Delivery of Antibiotics by 3D Core/Shell Printed Hydrogel Scaffolds to Treat Soft Tissue Infections.

Ashwini Rahul Akkineni,Michael Gelinsky,Anja Lode,Hubert Buechner,Michael Geissler,Saskia Reichelt,Janina Spangenberg

doi:10.3390/pharmaceutics13122151

Ashwini Rahul Akkineni, Michael Gelinsky + Show 5 more

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https://doi.org/10.3390/pharmaceutics13122151

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Abstract

Soft tissue infections in open fractures or burns are major cause for high morbidity in trauma patients. Sustained, long-term and localized delivery of antimicrobial agents is needed for early eradication of these infections. Traditional (topical or systemic) antibiotic delivery methods are associated with a variety of problems, including their long-term unavailability and possible low local concentration. Novel approaches for antibiotic delivery via wound coverage/healing scaffolds are constantly being developed. Many of these approaches are associated with burst release and thus seldom maintain long-term inhibitory concentrations. Using 3D core/shell extrusion printing, scaffolds consisting of antibiotic depot (in the core composed of low concentrated biomaterial ink 3% alginate) surrounded by a denser biomaterial ink (shell) were fabricated. Denser biomaterial ink (composed of alginate and methylcellulose or alginate, methylcellulose and Laponite) retained scaffold shape and modulated antibiotic release kinetics. Release of antibiotics was observed over seven days, indicating sustained release characteristics and maintenance of potency. Inclusion of Laponite in shell, significantly reduced burst release of antibiotics. Additionally, the effect of shell thickness on release kinetics was demonstrated. Amalgamation of such a modular delivery system with other biofabrication methods could potentially open new strategies to simultaneously treat soft tissue infections and aid wound regeneration.

Highlights

Patients with open fractures and severe burns, are often presented in clinics with extensive soft tissue damage
Biomaterial ink composed of alginate, methylcellulose and Laponite (ALG-MC-LAP) was prepared by first making a blend of 3% alginate and 3% Laponite (Laponite XLG, BYK additives & instruments, Widnes, UK; autoclaved Laponite powder was added to 3% alginate solution and was stirred overnight); followed by addition of 6%
Alginate-based hydrogels, along with the 3D core/shell extrusion printing method, were used to develop a hydrogel based antibiotic delivery system intended for treating soft tissue infections in open fractures and burn wounds

Summary

Introduction

Patients with open fractures and severe burns (with >20% burned body surface), are often presented in clinics with extensive soft tissue damage. Such soft tissue wounds are often at a high risk of infection, as the soft tissue of the skin is directly exposed to contaminants after a high-energy trauma (e.g., road or fire accidents). These contaminants and/or surgical treatment procedures can introduce microorganisms at the damaged soft tissue, potentially leading to an invasive infection [1]. Reconstructive surgical intervention might be needed depending on the severity of the wound to aid the healing process [3,4]

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