Abstract

Covalently cross-linked gels are utilized in a broad range of biomedical applications though their synthesis often compromises easy implementation. Cross-linking reactions commonly utilize catalysts or conditions that can damage biologics and sensitive compounds, producing materials that require extensive post processing to achieve acceptable biocompatibility. As an alternative, we report a batch synthesis platform to produce covalently cross-linked materials appropriate for direct biomedical application enabled by green chemistry and commonly available food grade ingredients. Using caffeine, a mild base, to catalyze anhydrous carboxylate ring-opening of diglycidyl-ether functionalized monomers with citric acid as a tri-functional crosslinking agent we introduce a novel poly(ester-ether) gel synthesis platform. We demonstrate that biocompatible Caffeine Catalyzed Gels (CCGs) exhibit dynamic physical, chemical, and mechanical properties, which can be tailored in shape, surface texture, solvent response, cargo release, shear and tensile strength, among other potential attributes. The demonstrated versatility, low cost and facile synthesis of these CCGs renders them appropriate for a broad range of customized engineering applications including drug delivery constructs, tissue engineering scaffolds, and medical devices.

Highlights

  • Robust and reproducible manufacturing of biocompatible materials with advanced functional properties is necessary to support the rapid growth and evaluation of novel biomedical technologies, especially with the rise of combination devices and the need for minimally invasive surgical techniques

  • Motivated by the emergence of vitrimers and concepts of dynamic thermosets [6e12] and covalent networks [25e28], we developed a novel class of materials within this family appropriate for accelerated and simplified translation to clinical application

  • The synthetic conditions allow direct drug loading during manufacturing and controlled release when incubated in in vitro or in vivo aqueous environments. This process is designed to be accessible to all minimally equipped biomedical engineering labs and represents a new class of materials able to provide broad functionality in a diverse set of applications ranging from drug delivery to food science

Read more

Summary

Introduction

Robust and reproducible manufacturing of biocompatible materials with advanced functional properties is necessary to support the rapid growth and evaluation of novel biomedical technologies, especially with the rise of combination devices and the need for minimally invasive surgical techniques. Crosslinked thermosets provide unique advantages for structural engineering by offering robust mechanical properties but often rely on complicated processing conditions using harsh solvents, high temperatures, or toxic catalysts that preclude direct implementation in biomedical applications [1e12] Polymer assemblies such as hydrogels maintain dynamic interaction with in vivo fluids enabling bioresponsive functions such as delivery of cargo, adsorption, and scaffolding [4e17]. This report explores three variations of the caffeine-catalyzed gel (CCGs) concept (Scheme 1), with a focus on utilization of FDA recognized biocompatible and ingestible materials such as polyethylene glycol, polypropylene glycol and citric acid This modular reaction platform is compatible with many combinations of multifunctional carboxylic acid/epoxy containing monomer pairs enabling diverse libraries of gels with customizable network properties. Innovations in drug delivery and device engineering will benefit from the reproducible and robust manufacturing methods that employ readily available feedstocks to construct functional novel materials

Materials
Representative polymer synthesis
Fourier transform infrared spectroscopy
Scanning electron microscopy
Contact angle goniometry
Hydration kinetics
Mechanical characterization
Self-healing
2.11. LC50 cytotoxicity study
2.12. Acute oral toxicity test
Results
Discussion
Findings
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call