Development of Hydrogel-Cellulose Nanofiber Hybrid Scaffolds for Potential Cutaneous Wound-Healing Applications

Cellulose nanofibrils (CNFs) and TEMPO-oxidized cellulose nanofibrils (TOCNFs) are hydrated, high-aspect-ratio biomaterials with tunable physicochemical properties, whereas human-derived extracellular matrix (ECM) hydrogels provide matrix-associated biochemical cues. In this study, CNF- and TOCNF-based hybrid scaffolds incorporating human ECM hydrogel components were developed and evaluated in vitro as platforms relevant to cutaneous wound repair. Hybrid formulations gelled at physiological temperature and exhibited formulation-dependent shear-thinning behavior, elastic properties, protein release/leaching profiles, and porous fibrillar microstructures. Selected formulations supported cell-associated metabolic activity of human dermal fibroblasts and adipose-derived stromal/stem cells under two-dimensional and three-dimensional culture conditions. Additional exploratory studies demonstrated qualitative compatibility with adipogenic culture and condition-dependent changes in wound-gap width. In the absence of in vivo validation and confirmatory biological assays, these findings are interpreted as proof-of-concept rather than evidence of wound-healing efficacy. Overall, the results demonstrate the feasibility of combining CNF or TOCNF structural networks with human-derived ECM hydrogels to generate hybrid scaffolds with wound-relevant material properties and preliminary cytocompatibility, supporting further mechanistic and preclinical evaluation.