{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T23:16:59Z","timestamp":1778195819150,"version":"3.51.4"},"reference-count":51,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gels"],"abstract":"<jats:p>Chronic wounds are a major health problem, affecting millions of people worldwide. Resistance to treatment is frequently observed, requiring an extension of the wound healing time, and improper care can lead to more problems in patients. Smart wound dressings that provide a controlled drug release can significantly improve the healing process. In this paper, alginate beads with white lily leaf extract were prepared and tested for chronic wound healing. The obtained beads were characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). Also, the efficiency of extract encapsulation in alginate was determined as being of. The obtained hydrogel was tested on two normal human cell lines, respectively, dermal fibroblasts (BJ-CRL-2522-ATCC) and endothelial cells (human umbilical vein endothelial cells\u2014HUVEC 2). The longer release of bioactive compounds from plant extract loaded in the alginate hydrogel resulted in more effective wound closure, compared to the extract alone, and scar formation, compared to the alginate hydrogel. Therefore, the effect of the white lily extract in combination with that of sodium alginate hydrogel improves the biological activity of the alginate hydrogel and increases the wound healing properties of the alginate.<\/jats:p>","DOI":"10.3390\/gels11010022","type":"journal-article","created":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T11:24:19Z","timestamp":1735730659000},"page":"22","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Lilium candidum Extract Loaded in Alginate Hydrogel Beads for Chronic Wound Healing"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4046-7310","authenticated-orcid":false,"given":"Ioana","family":"B\u00e2ldea","sequence":"first","affiliation":[{"name":"Department of Physiology, Iuliu Ha\u0163ieganu University of Medicine and Pharmacy, Clinicilor 1, 400006 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3770-9702","authenticated-orcid":false,"given":"Maria-Loredana","family":"Soran","sequence":"additional","affiliation":[{"name":"National Institute for Research and Development of Isotopic and Molecular Technologies, 67-103 Donath, 400293 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adina","family":"Stegarescu","sequence":"additional","affiliation":[{"name":"National Institute for Research and Development of Isotopic and Molecular Technologies, 67-103 Donath, 400293 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9765-2739","authenticated-orcid":false,"given":"Ocsana","family":"Opri\u0219","sequence":"additional","affiliation":[{"name":"National Institute for Research and Development of Isotopic and Molecular Technologies, 67-103 Donath, 400293 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina","family":"Kacso","sequence":"additional","affiliation":[{"name":"National Institute for Research and Development of Isotopic and Molecular Technologies, 67-103 Donath, 400293 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Septimiu","family":"Tripon","sequence":"additional","affiliation":[{"name":"National Institute for Research and Development of Isotopic and Molecular Technologies, 67-103 Donath, 400293 Cluj-Napoca, Romania"},{"name":"Electron Microscopy Center, Babes-Bolyai University, 400006 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Adascalitei","sequence":"additional","affiliation":[{"name":"Department of Physiology, Iuliu Ha\u0163ieganu University of Medicine and Pharmacy, Clinicilor 1, 400006 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iulian George","family":"Fericel","sequence":"additional","affiliation":[{"name":"Department of Physiology, Iuliu Ha\u0163ieganu University of Medicine and Pharmacy, Clinicilor 1, 400006 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roxana","family":"Decea","sequence":"additional","affiliation":[{"name":"Department of Physiology, Iuliu Ha\u0163ieganu University of Medicine and Pharmacy, Clinicilor 1, 400006 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ildiko","family":"Lung","sequence":"additional","affiliation":[{"name":"National Institute for Research and Development of Isotopic and Molecular Technologies, 67-103 Donath, 400293 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8856","DOI":"10.1039\/C5TB01758K","article-title":"Design of a thermosensitive bioglass\/agarose alginate composite hydrogel for chronic wound healing","volume":"3","author":"Zeng","year":"2015","journal-title":"J. Mater. Chem. B"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"295","DOI":"10.4155\/tde-2021-0087","article-title":"Dissolvable wound dressing loaded with silver nanoparticles together with ampicillin and ciprofloxacin","volume":"13","author":"Ndlovu","year":"2022","journal-title":"Ther. Deliv."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Barbu, A., Neamtu, B., Z\u0103han, M., Iancu, G.M., Bacila, C., and Mire\u0219an, V. (2021). Current trends in advanced alginate-based wound dressings for chronic wounds. J. Pers. Med., 11.","DOI":"10.3390\/jpm11090890"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"451","DOI":"10.12688\/f1000research.52528.1","article-title":"Formulation and characterisation of alginate hydrocolloid film dressing loaded with gallic acid for potential chronic wound healing","volume":"10","author":"Chin","year":"2021","journal-title":"F1000Research"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e202000507","DOI":"10.1590\/s0102-865020200050000007","article-title":"Evaluation of wound healing effect of alginate film containing aloe vera gel and cross-linked with zinc chloride","volume":"35","author":"Koga","year":"2020","journal-title":"Acta Cir. Bras."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"153636","DOI":"10.1016\/j.phymed.2021.153636","article-title":"Wound healing properties of flavonoids: A systematic review highlighting the mechanisms of action","volume":"90","author":"Carvalho","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Majtan, J., and Jesenak, M. (2018). \u03b2-Glucans: Multi-functional modulator of wound healing. Molecules, 23.","DOI":"10.3390\/molecules23040806"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4749712","DOI":"10.1155\/2020\/4749712","article-title":"Chemical characterization and wound healing property of Jacaranda decurrens cham. (Bignoniaceae): An experimental study based on molecular mechanisms","volume":"2020","author":"Serra","year":"2020","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1002\/ptr.6102","article-title":"Natural actives for wound healing: A review","volume":"32","author":"Ataide","year":"2018","journal-title":"Phytother. Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ishfaq, B., Khan, I.U., Khalid, S.H., and Asghar, S. (2023). Design and evaluation of sodium alginate-based hydrogel dressings containing Betula utilis extract for cutaneous wound healing. Front. Bioeng. Biotechnol., 11.","DOI":"10.3389\/fbioe.2023.1042077"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"111667","DOI":"10.1016\/j.msec.2020.111667","article-title":"Advanced SA\/PVA-based hydrogel matrices with prolonged release of Aloe vera as promising wound dressings","volume":"120","author":"Pluta","year":"2021","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Santos, L.G., Silva, G.F.A., Gomes, B.M., and Martins, V.G. (2021). A novel sodium alginate active films functionalized with purple onion peel extract (Allium cepa). Biocatal. Agric. Biotechnol., 35.","DOI":"10.1016\/j.bcab.2021.102096"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Luo, Y., Liu, H., Yang, S., Zeng, J., and Wu, Z. (2019). Sodium alginate-based green packaging films functionalized by guava leaf extracts and their bioactivities. Materials, 12.","DOI":"10.3390\/ma12182923"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1177\/08839115211073155","article-title":"Production of alginate films containing Hypericum perforatum extract as an antibacterial and antioxidant wound dressing material","volume":"37","author":"Mutlu","year":"2022","journal-title":"J. Bioact. Compatible Polym."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.1007\/s12649-022-01710-3","article-title":"Characterization and antibacterial properties of novel biodegradable films based on alginate and roselle (Hibiscus sabdariffa L.) extract","volume":"13","author":"Aydin","year":"2022","journal-title":"Waste Biomass Valorization"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1080\/09205063.2024.2381375","article-title":"Sodium alginate-based nanofibers loaded with Capparis sepiaria plant extract for wound healing","volume":"35","author":"Ndlovu","year":"2024","journal-title":"J. Biomater. Sci. Polym. Ed."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"B\u00e2ldea, I., Lung, I., Opris, O., Stegarescu, A., Kacso, I., and Soran, M.-L. (2023). Antioxidant, anti-Inflammatory effects and ability to stimulate wound healing of a common-plantain extract in alginate gel formulations. Gels, 9.","DOI":"10.3390\/gels9110901"},{"key":"ref_18","first-page":"13859","article-title":"Bioactivity of Lilium candidum L.: A Mini Review","volume":"18","author":"Patocka","year":"2019","journal-title":"Biomed. J. Sci. Tech. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"634","DOI":"10.4103\/jfmpc.jfmpc_423_18","article-title":"Promising pain-relieving activity of an ancient Persian remedy (mixture of white Lily in sesame oil) in patients with chronic low back pain","volume":"8","author":"Rasoulinezhad","year":"2019","journal-title":"J. Family Med. Prim. Care"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"485","DOI":"10.4314\/ajtcam.v10i6.16","article-title":"A study on the extraction and purification process of lily polysaccharide and its anti-tumor effect","volume":"10","author":"Han","year":"2013","journal-title":"Afr. J. Trad. Compl. Allter. Med."},{"key":"ref_21","first-page":"725","article-title":"Evaluation of hepatoprotective activity of Lilium candidum L. in experimental animal models","volume":"5","author":"Devi","year":"2016","journal-title":"World J. Pharmaceu. Res."},{"key":"ref_22","first-page":"333","article-title":"Lily toxicity in cats","volume":"1","author":"Bates","year":"2015","journal-title":"Feline Focus"},{"key":"ref_23","first-page":"109","article-title":"Wound healing activity of the flowers of Lilium candidum L. in burn wound model in rats","volume":"19","author":"Momtaz","year":"2020","journal-title":"J. Med. Plants"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1039\/c3tb21509a","article-title":"Fabrication of alginate\u2013gelatin crosslinked hydrogel microcapsules and evaluation of the microstructure and physico-chemical properties","volume":"2","author":"Sarker","year":"2014","journal-title":"J. Mater. Chem. B"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1080\/01932691.2019.1611437","article-title":"Interactions between gelatin and sodium alginate: UV and FTIR studies","volume":"41","author":"Derkach","year":"2019","journal-title":"J. Dispers. Sci. Technol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Mormile, C., Opri\u0219, O., Bellucci, S., Lung, I., Kacso, I., Turza, A., La Pietra, M., Vacacela Gomez, C., Stegarescu, A., and Soran, M.-L. (2023). Enhanced stability of dopamine delivery via hydrogel with integrated graphene. J. Funct. Biomater., 14.","DOI":"10.3390\/jfb14120558"},{"key":"ref_27","first-page":"20","article-title":"Fourier transform infrared spectroscopy analysis of various solvent extracts of Caralluma fimbriyata","volume":"4","author":"Packialakshmi","year":"2014","journal-title":"Asian J. Biomed. Pharm. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s10973-012-2909-y","article-title":"FTIR, XRD, and DSC analysis of the rosemary extract effect on polyethylene structure and biodegradability","volume":"114","author":"Musuc","year":"2013","journal-title":"J. Therm. Anal. Calorim."},{"key":"ref_29","first-page":"33","article-title":"Comparative phenolic fingerprint and LC-ESI+QTOF-MS composition of oregano and rosemary hydrophilic extracts in relation to their antibacterial effect","volume":"72","author":"Bunghez","year":"2015","journal-title":"Bull. UASVM Food Sci. Technol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Honda, T., and Inagawa, H. (2023). Utility of in vitro cellular models of low-dose lipopolysaccharide in elucidating the mechanisms of anti-inflammatory and wound-healing-promoting effects of lipopolysaccharide administration in vivo. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241814387"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1002\/iub.1159","article-title":"Effect of lipopolysaccharide on the biological characteristics of human skin fibroblasts and hypertrophic scar tissue formation","volume":"65","author":"Yang","year":"2013","journal-title":"IUBMB Life"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1152\/ajplung.00338.2002","article-title":"Mechanisms of bacterial lipopolysaccharide-induced endothelial apoptosis","volume":"284","author":"Bannerman","year":"2003","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/j.1524-475X.2007.00290.x","article-title":"Inhibition of keratinocyte migration by lipopolysaccharide","volume":"16","author":"Loryman","year":"2008","journal-title":"Wound Repair. Regen."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1016\/j.burns.2023.06.005","article-title":"Lipopolysaccharide induces skin scarring through the TLR4\/Myd88 inflammatory signaling pathway in dermal fibroblasts","volume":"49","author":"Xu","year":"2023","journal-title":"Burns"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1002\/(SICI)1097-4644(19960301)60:3<379::AID-JCB9>3.0.CO;2-T","article-title":"Temporal study of the activity of matrix metalloproteinases and their endogenous inhibitors during wound healing","volume":"60","author":"Moses","year":"1996","journal-title":"J. Cell. Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6645766","DOI":"10.1155\/2021\/6645766","article-title":"IL-1\u03b2 impaired diabetic wound healing by regulating MMP-2 and MMP-9 through the p38 pathway","volume":"2021","author":"Dai","year":"2021","journal-title":"Mediators Inflamm."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s00726-010-0689-x","article-title":"Physiology and pathophysiology of matrix metalloproteases","volume":"41","author":"Klein","year":"2011","journal-title":"Amino Acids."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1089\/wound.2014.0581","article-title":"O\u2019Toole EA. Metalloproteinases and wound healing","volume":"4","author":"Caley","year":"2015","journal-title":"Adv. Wound Care"},{"key":"ref_39","first-page":"275","article-title":"The role of matrix metalloproteinase-9 and its inhibitor TIMP-1 in burn injury: A systematic review","volume":"11","author":"Sharma","year":"2021","journal-title":"Int. J. Burns. Trauma"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Chumpolphant, S., Suwatronnakorn, M., Issaravanich, S., Tencomnao, T., and Prasansuklab, A. (2022). Polyherbal formulation exerts wound healing, anti-inflammatory, angiogenic and antimicrobial properties: Potential role in the treatment of diabetic foot ulcers. Saudi J. Biol. Sci., 29.","DOI":"10.1016\/j.sjbs.2022.103330"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"7162","DOI":"10.1111\/febs.15701","article-title":"Multifunctional intracellular matrix metalloproteinases: Implications in disease","volume":"288","author":"Bassiouni","year":"2021","journal-title":"FEBS J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/ptr.912","article-title":"Effect of a lipopolysaccharide from E. coli on the proliferation of fibroblasts and keratinocytes in vitro","volume":"16","author":"Yang","year":"2002","journal-title":"Phytother. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.cjtee.2023.06.005","article-title":"Enteral glutamine supplements for patients with severe burns: A systematic review and meta-analysis","volume":"27","author":"Yue","year":"2024","journal-title":"Chin. J. Traumatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1002\/kjm2.12654","article-title":"Lavender essential oil accelerates lipopolysaccharide-induced chronic wound healing by inhibiting caspase-11-mediated macrophage pyroptosis","volume":"39","author":"Ao","year":"2023","journal-title":"Kaohsiung J. Med. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"45","DOI":"10.2298\/JSC1001045I","article-title":"Determination of the polyphenol contents in Macedonian grapes and wines by standardized spectrophotometric methods","volume":"75","author":"Ivanova","year":"2010","journal-title":"J. Serb. Chem. Soc."},{"key":"ref_46","first-page":"25","article-title":"Use of a free radical method to evaluate antioxidant activity","volume":"28","author":"Cuvelier","year":"1995","journal-title":"LWT\u2015Food Sci. Technol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"479","DOI":"10.3390\/polym6020479","article-title":"Antimicrobial plant extracts encapsulated into polymeric beads for potential application on the skin","volume":"6","author":"Rijo","year":"2014","journal-title":"Polymers"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1016\/j.foodhyd.2016.06.039","article-title":"Alginate-based encapsulation of polyphenols from Clitoria ternatea petal flower extract enhances stability and biological activity under simulated gastrointestinal conditions","volume":"61","author":"Pasukamonset","year":"2016","journal-title":"Food Hydrocoll."},{"key":"ref_49","unstructured":"(2012). Biological Evaluation of Medical Devices\u2014PART 12: Sample Preparation and Reference Materials (Standard No. ISO 10993-12:2012)."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Baldea, I., Petran, A., Florea, A., Sevastre-Berghian, A., Nenu, I., Filip, G.A., Cenariu, M., Radu, M.T., and Iacovita, C. (2023). Magnetic nanoclusters stabilized with poly [3,4-dihydroxybenzhydrazide] as efficient therapeutic agents for cancer cells destruction. Nanomaterials, 13.","DOI":"10.3390\/nano13050933"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Filip, M., Baldea, I., David, L., Moldovan, B., Flontas, G.C., Macavei, S., Muntean, D.M., Decea, N., Tigu, A.B., and Clichici, S.V. (2023). Hybrid material based on Vaccinium myrtillus L. extract and gold nanoparticles reduces oxidative stress and inflammation in hepatic stellate cells exposed to TGF-\u03b2. Biomolecules, 13.","DOI":"10.3390\/biom13081271"}],"container-title":["Gels"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2310-2861\/11\/1\/22\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T15:23:06Z","timestamp":1759850586000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2310-2861\/11\/1\/22"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,1]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["gels11010022"],"URL":"https:\/\/doi.org\/10.3390\/gels11010022","relation":{},"ISSN":["2310-2861"],"issn-type":[{"value":"2310-2861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,1]]}}}