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However, cost-effective regenerative strategies are still limited in veterinary practice. This study aimed to develop and evaluate a novel tannic acid (TA)\u2013gelatin-based hydrogel (Gel), incorporating graphene oxide (GO) and hydroxyapatite nanoparticles (HA), as a potential barrier material for guided tissue regeneration (GTR) applications. The hydrogels\u2014Gel, Gel-GO, Gel-HA, and Gel-GO-HA\u2014were characterized for chemical structure, molecular interactions, surface morphology, nanoparticle dispersion, and tensile strength. Cytotoxicity was assessed using L929 fibroblasts (ISO 10993-5), while cell viability\/proliferation, morphology, and alkaline phosphatase (ALP) production were evaluated using canine periodontal ligament-derived cells. Results show that crosslinking with tannic acid enhanced the incorporation of graphene oxide and hydroxyapatite nanoparticles via hydrogen bonding into TA\u2013gelatin-based hydrogels. This combination increased surface roughness, reduced degradation rate, and enabled shape memory behavior, critical for guided tissue regeneration (GTR) membranes. The extracts from Gel-HA-GO showed that cytotoxicity was both time- and concentration-dependent in L929 fibroblasts, whereas enhanced cell proliferation and increased ALP production were observed in cultures derived from canine periodontal ligament cells. These findings suggest that TA\u2013gelatin-based hydrogels incorporating GO and HA demonstrated favorable mechanical and physicochemical properties, biocompatibility, and osteogenic potential. These attributes suggest their viability as a promising composite for the development of innovative GTR strategies to address periodontal tissue loss in veterinary medicine.<\/jats:p>","DOI":"10.3390\/gels11080650","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T16:09:55Z","timestamp":1755274195000},"page":"650","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Tannic Acid-Enhanced Gelatin-Based Composite Hydrogel as a Candidate for Canine Periodontal Regeneration"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1584-229X","authenticated-orcid":false,"given":"Laura C.","family":"Pinho","sequence":"first","affiliation":[{"name":"BoneLab, Faculdade de Medicina Dent\u00e1ria, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal"},{"name":"LAQV\/REQUIMTE, Faculdade de Medicina Dent\u00e1ria, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal"},{"name":"Centre for Research and Technology of Agro-Environmental and Biological Sciences, CITAB, Inov4Agro, University of Tr\u00e1s-os-Montes and Alto Douro, UTAD, Quinta de Prados, 5000-801 Vila Real, Portugal"},{"name":"CQE, IMS, Instituto Superior T\u00e9cnico, University of Lisbon, 1049-001 Lisbon, Portugal"},{"name":"Instituto Polit\u00e9cnico de Set\u00fabal, EST Set\u00fabal, Campus IPS-Estefanilha, 2910-761 Set\u00fabal, Portugal"}]},{"given":"Marta","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Instituto Polit\u00e9cnico de Set\u00fabal, EST Set\u00fabal, Campus IPS-Estefanilha, 2910-761 Set\u00fabal, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9829-0733","authenticated-orcid":false,"given":"Ang\u00e9lica","family":"Gra\u00e7a","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, Avenida Professor Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5523-5622","authenticated-orcid":false,"given":"Joana","family":"Marto","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, Avenida Professor Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4879-8624","authenticated-orcid":false,"given":"Bruno","family":"Cola\u00e7o","sequence":"additional","affiliation":[{"name":"Centre for Research and Technology of Agro-Environmental and Biological Sciences, CITAB, Inov4Agro, University of Tr\u00e1s-os-Montes and Alto Douro, UTAD, Quinta de Prados, 5000-801 Vila Real, Portugal"},{"name":"CECAV\u2014Veterinary and Animal Research Centre, AL4AnimalS, Universidade de Tr\u00e1s-os-Montes e Alto Douro, UTAD, Quinta de Prados, 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9391-9574","authenticated-orcid":false,"given":"Maria Helena","family":"Fernandes","sequence":"additional","affiliation":[{"name":"BoneLab, Faculdade de Medicina Dent\u00e1ria, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal"},{"name":"LAQV\/REQUIMTE, Faculdade de Medicina Dent\u00e1ria, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8567-0032","authenticated-orcid":false,"given":"Catarina","family":"Santos","sequence":"additional","affiliation":[{"name":"CQE, IMS, Instituto Superior T\u00e9cnico, University of Lisbon, 1049-001 Lisbon, Portugal"},{"name":"Instituto Polit\u00e9cnico de Set\u00fabal, EST Set\u00fabal, Campus IPS-Estefanilha, 2910-761 Set\u00fabal, Portugal"},{"name":"Research Institute for Medicines (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, Avenida Professor Gama Pinto, 1649-003 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Cunha, E., Tavares, L., and Oliveira, M. 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