Towards Tunable Protein-Carrier Wound Dressings Based on Nanocellulose Hydrogels Crosslinked with Calcium Ions.

Alex Basu,Maria Strømme,Natalia Ferraz

doi:10.3390/nano8070550

Abstract

A Ca2+-crosslinked wood-based nanofibrillated cellulose (NFC) hydrogel was investigated to build knowledge toward the use of nanocellulose for topical drug delivery applications in a chronic wound healing context. Proteins of varying size and isoelectric point were loaded into the hydrogel in a simple soaking procedure. The release of the proteins from the hydrogel was monitored and kinetics determining parameters of the release processes were assessed. The integrity of the hydrogel and proteins were also studied. The results showed that electrostatic interactions between the proteins and the negatively-charged NFC hydrogel structure played a central role in the loading process. The release of the proteins were governed by Fickian diffusion. An increased protein size, as well as a positive protein charge facilitated a slower and more sustained release process from the hydrogel matrix. At the same time, the positively-charged protein was shown to increase the post-loading hydrogel strength. Released proteins maintained structural stability and activity, thus indicating that the Ca2+-crosslinked NFC hydrogel could function as a carrier of therapeutic proteins without compromising protein function. It is foreseen that, by utilizing tunable charge properties of the NFC hydrogel, release profiles can be tailored to meet very specific treatment needs.

Highlights

Wound dressings based on wood-derived nanofibrillated cellulose (NFC) hydrogels have been identified as promising candidates for advanced wound healing applications owing to their biocompatibility, hemocompatibility, and modifiable nature [1,2,3,4,5,6,7]
Unmodified biocide-free NFC prepared from never-dried bleached sulfite softwood pulp as described by Pääkkö et al [29] was provided by RISE Bioeconomy (Stockholm, Sweden). 2-mercaptoethanol (2-ME), 2,2,6,6tetramethylpiperidine-1-oxyl (TEMPO), bovine serum albumin (BSA), Ca(NO3)2, ethanol, lysozyme, NaBr, NaClO, NaOH, and peptone water were purchased from Sigma-Aldrich (Saint Louis, MO, USA)
The results presented on material and protein stability after loading and release highlight the potential of using the NFC hydrogel as a wound healing dressing with the ability to carry and deliver therapeutic proteins

Summary

Introduction

Wound dressings based on wood-derived nanofibrillated cellulose (NFC) hydrogels have been identified as promising candidates for advanced wound healing applications owing to their biocompatibility, hemocompatibility, and modifiable nature [1,2,3,4,5,6,7]. NFC consists of fibrils with a diameter of 3–5 nm and a length of several micrometers that arrange in aggregates of 20–50 nm due to strong intramolecular interactions [8]. The abundancy of this bio-polymer makes it an intriguing alternative to synthetic and animal-based polymers for the use in wound healing applications [8,9,10]. Examples of therapeutic agents that are relevant in a wound healing context are growth factors for improved tissue regeneration (e.g., platelet-derived growth factor (PDGF)) [22]; cytokines that trigger anti-inflammatory processes (e.g., IL-10) [23]; and non-antibiotic antibacterial agents for the resolution of wound infections [24]

Objectives

Methods

Results

Conclusion