Growth factor functionalized biodegradable nanocellulose scaffolds for potential wound healing application

Nanocellulose has been highlighted as one of the most promising biomaterials for biomedical applications with the potential to outperform conventional polymeric materials. However, the design of nanocellulose-based biomaterials for wound healing still requires precise control over biophysical and biochemical cues to direct a series of cellular activities in healing processes. The bioactive cellulose nanofibrils scaffolds with controlled release of basic fibroblast growth factors (bFGFs) were constructed for potential wound healing applications. The Quartz Crystal Microbalance with Dissipation monitoring (QCM-D) analysis revealed the polyion complex interaction between the positively charged bFGFs with the negatively charged cellulose nanofibrils, which mimics the interaction between bFGFs and heparin sulfate in extracellular matrix in the body. Such association enables not only the storage of bFGFs in a readily available form and from where it is slowly released, but also potential protection of it from denaturation. The release profile of bFGFs from the CNF scaffolds was tailored by tuning the CNF surface chemistry and in situ deconstruction of the scaffolds. The in situ enzymatic deconstruction of the scaffolds provides a possibility to tune the bioavailability of bFGFs for cell growth and proliferation, and more importantly, to balance the scaffolds degradation and new tissue formation in wound healing. The MTT assay of cells proliferation and fluorescence imaging of cells cultured in the 3D scaffolds showed that the CNF scaffolds loaded with bFGF can significantly facilitate the proliferation of the cells, even if only a small amount of bFGF was loaded. Enzymatic deconstruction of the CNFs network further increases the bFGFs bioavailability, and promotes cell proliferation. This work may serve as an important step toward the development of nanocellulose-based biomaterials with tailored biophysical and biochemical cues for wound healing and other biomedical applications.