From Waste to Worth: Green and Scalable Extraction Technologies for Grape By-Product Valorization

The valorization of grape by-products, such as grape pomace, skins, seeds, stalks, leaves, and vine shoots, represents a strategic pathway within the circular bioeconomy, offering opportunities to recover high-value bioactive compounds from the residues of the wine industry [1]. These materials are rich in polyphenols, pectins, and oligosaccharides, with recognized antioxidant, antimicrobial, and prebiotic properties, and therefore hold considerable potential for highadded-value applications in the food, nutraceutical, and pharmaceutical sectors. Moreover, their lignocellulosic nature, containing cellulose, hemicellulose, and lignin, makes them interesting substrates for integrated biorefinery strategies. Traditional extraction methods often rely on hazardous solvents, long processing times, and high energy input, which limit their sustainability [2,3]. Over the past decade, our research has focused on applying and optimizing non-conventional, green extraction techniques - including ultrasound-assisted (UAE), microwave-assisted (MAE), and subcritical water extraction (with and without microwave assistance, SWE) - at both laboratory and pilot scale. The objective has been to selectively recover functional compounds and structural biopolymers from grape industrial residues, ultimately integrating chemical and biological approaches to maximize resource efficiency and support the sustainable production of bio-based ingredients. For grapevine shoots and leaves, lab-scale UAE and MAE were optimized for polyphenol content and antioxidant capacity using various green solvents, with energy consumption and extraction efficiency also assessed [4]. Subcritical water extraction (SWE) was recently applied to similar residues at pilot scale to maximize polyphenol recovery while enhancing process sustainability. Extensive UAE studies were conducted on grape stalks, from lab to semi-industrial scale (15 L reactor), using only water and integrating nanofiltration to concentrate polyphenolic extracts [5]. Key parameters such as temperature and particle size were optimized. Additionally, microwave-assisted SWE (MASWE) was employed to recover polyphenols and pectins from grape stalks, followed by acid, ultrasound, and combined hydrolysis to assess their effects on pectin properties and prebiotic potential. MAE was also applied to the residual solid fraction for delignification purposes [6]. Grape pomace phenolics were initially extracted at lab scale using UAE and MAE, similar to shoots and leaves. MASWE was then optimized and benchmarked against conventional methods across several grape varieties, both at lab and pilot scale (16-fold scale-up), with extracts evaluated for antioxidant and anti-cancer properties. Finally, grape seed proteins were extracted in basic aqueous medium via UAE at both lab and pilot scale (5 kg feedstock), with pH optimization for protein precipitation and characterization of the protein-rich fractions for nutritional value and safety [7]. Our investigations consistently demonstrated that non-conventional extraction technologies significantly enhance the recovery of high-value compounds from grape by-products. Both lab-scale UAE and MAE improved the extraction of polyphenols and antioxidant activity from grapevine shoots and leaves, with considerable energy savings compared to conventional maceration [4]. Pilot-scale SWE on grape pruning residues yielded extracts with promising biological activity. For grape stalks, pilot-scale UAE in water effectively recovered polyphenols with high antioxidant capacity, while subsequent nanofiltration allowed extract concentration and 80% water recovery, reinforcing the process’s greenness [5]. MASWE applied to grape stalks produced phenolic extracts with proven antioxidant and antimicrobial properties, and pectin fractions with enhanced prebiotic potential, particularly after ultrasonic hydrolysis, which supported probiotic bacterial growth. This protocol was characterized by a multidisciplinary approach to minimizing by-products [6]. MASWE also proved to be a fast and efficient method for grape pomace valorization, yielding antioxidant- and anticancer-active phenolic fractions and demonstrating successful scale-up. Lastly, UAE significantly improved protein recovery from grape seeds at both lab and pilot scale, delivering protein-rich extracts free from hazardous contaminants and suitable for food or nutraceutical applications [7]. Overall, these results support the advancement of circular bioeconomy by demonstrating how grape-derived agricultural residues can serve as strategic feedstocks for the sustainable production of functional ingredients and biomolecules with high industrial relevance. [1] Genisheva, Z.; Soares, M.; Oliveira, J.M.; Carvalho, J. Wine Production Wastes, Valorization, and Perspectives. In Advances and Challenges in Hazardous Waste Management; IntechOpen: London, UK, 2023; Vol. 25, pp. e275–e281. ISBN 0000957720. [2] Chemat, F.; Vian, M.A.; Cravotto, G. Green extraction of natural products: concept and principles. International Journal Molecular Sciences 2012, 13(7), 8615-8627. https://doi:10.3390/ijms13078615. [3] Voss, M.; Calcio Gaudino, E.; Tabasso, S.; Forte, C., Cravotto, G. Current Emerging Green Technologies for the Valorization of Grape and Cherry Wastes. Current Food Science Technology Reports 2023, 1, 47–61. https://doi.org/10.1007/s43555-023-00010-8. [4] Alexandru L.; Binello A.; Mantegna S.; Boffa L.; Chemat F.; Cravotto G. Efficient green extraction of polyphenols from post-harvested agro- industry vegetal sources in Piedmont. Comptes Rendus. Chimie 2014, 17(3), 212-217. https://doi.org/10.1016/j.crci.2013.09.012. [5] Grillo, G.; Boffa, L.; Talarico, S.; Solarino, R.; Binello, A.; Cavaglià, G.; Bensaid, S.; Telysheva, G.; Cravotto, G. Batch and Flow Ultrasound- Assisted Extraction of Grape Stalks: Process Intensification Design up to a Multi-Kilo Scale. Antioxidants 2020, 9, 730. https://doi.org/10.3390/antiox9080730. [6] Valle, C.; Grillo, G.; Calcio Gaudino, E.; Ponsetto, P.; Mazzoli, R.; Bonavita, G.; Vitale, P.; Pessione, E.; GarciaMoruno, E.; Costantini, A.; Cravotto, G.; Tabasso, S. ChemSusChem 2025, 18, e202402536. https://doi.org/10.1002/cssc.202402536. [7] Chaji, S.; Capaldi, G.; Gallina, L.; Grillo, G.; Boffa, L; Cravotto, G. Semi-industrial ultrasound-assisted extraction of grape-seed proteins. Journal Science Food Agriculture 2024, 104(10), 5689-5697. https://doi:10.1002/jsfa.13395