From Coffee Waste to Bioactive Hydrogels: In Situ Antioxidant Functionalization of Bacterial Cellulose During Biosynthesis

Abstract

Bacterial cellulose (BC) is a highly biocompatible nanofibrillar hydrogel widely explored for wound healing and tissue engineering; however, its intrinsic lack of bioactivity limits its use in advanced regenerative applications. Here, we report a one-step biosynthetic strategy that employs spent coffee grounds (SCG) extract as a dual-function cultivation medium, enabling simultaneous BC production and in situ biofunctionalization. The SCG extract fully replaced glucose in Hestrin–Schramm medium, providing fermentable sugars together with naturally occurring bioactive compounds that support cellulose biosynthesis by Komagataeibacter xylinus at a level comparable to that achieved with glucose-based cultivation. The resulting SCG-modified BC (SCG-BC) maintained a continuous nanofibrillar network while exhibiting altered supramolecular organization, including changes in molecular weight, swelling behavior, and hydrogel mechanics. Importantly, SCG-BC displayed strong and sustained antioxidant activity (200.23 ± 59.14 mg TE g–1), indicating stable incorporation of redox-active SCG-derived constituents and limited leaching under aqueous conditions. Biological evaluation demonstrated enhanced metabolic activity of human Wharton’s jelly-derived mesenchymal stromal cells and dermal fibroblasts on SCG-BC compared with native BC, while supporting cell viability under direct-contact conditions. An in vivo-like assessment using the quail chorioallantoic membrane model revealed a modulated angiogenic response characterized by altered vessel density and branching without suppression of overall vascular development. Collectively, these results demonstrate that SCG-derived components can be integrated during bacterial cellulose biosynthesis to generate structurally intact, antioxidant-active, and biofunctional hydrogels while enabling sustainable utilization of an agro-industrial waste stream. This approach establishes a structure–bioactivity framework for engineering multifunctional BC-based biomaterials for skin-contact and wound-healing applications.