In Vitro and in Vivo Evaluation of the Wound Healing Properties of Nanofibrillated Cellulose Hydrogels

Abstract

Current trends in wound care research move toward the development of wound healing dressings designed to treat different types of wounds (e.g., burns and chronic wounds) and toward tailoring treatments for different stages of the wound healing process. In this context, the development of advanced nanotherapeutic materials is highlighted as a promising strategy to efficiently control specific phases of the wound healing process. Here, Ca²⁺-cross-linked wood-derived nanofibrillated cellulose (NFC) hydrogels are evaluated as wound healing dressings. In vitro biocompatibility assays were performed to study the interaction of the NFC hydrogels with cellular processes that are tightly related to wound healing. Moreover, an in vivo dermo-epidermic full thickness wound healing model in rat was used to uncover the wound healing ability of the Ca²⁺-cross-linked NFC hydrogels. The in vitro experiments showed that the NFC hydrogels were able to support fibroblast and keratinocyte proliferation. A potential effect of the hydrogels on triggering keratinocyte differentiation was furthermore proposed. In vivo, the NFC hydrogels stimulated healing without causing any adverse local tissue effects, potentially owing to their moisture-donating properties and the herein discussed aiding effect of the Ca²⁺-cross-linker on epidermal generation. Thus, this work extensively demonstrates the wound healing ability of NFC hydrogels and presents an important milestone in the research on NFC toward advanced wound healing applications.

Keywords: fibroblasts; in vivo; ion-cross-linking; keratinocytes; nanocellulose; scratch test.