Skin aging involves changes in extracellular matrix components, such as wrinkles and pigmentation. Caviar extract (CE) is a promising compound for skin rejuvenation, but effective topical delivery requires optimized carriers. This study evaluated polyvinyl alcohol/carboxymethyl chitosan (PVA/CMC) hydrogels loaded with CE at concentrations of 2%, 3.5%, and 5% as scaffolds to influence the epithelial differentiation of adipose-derived mesenchymal stem cells (ADMSCs). Hydrogels were synthesized using a freeze-thaw method and characterized by Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy, swelling and degradation tests, and mechanical analysis. Biocompatibility and cell migration were assessed using MTT and scratch assays; at the same time, expression of cytokeratin-18 (CK-18) and pan-cytokeratin (pan-CK) was measured via reverse transcription-quantitative polymerase chain reaction and immunocytochemistry (ICC), respectively. FTIR confirmed successful CE incorporation, and SEM revealed a porous structure. Hydrogels with 3.5% and 5% CE demonstrated a good balance between swelling and degradation over 336 h. The biocompatibility tests showed that 5% CE supported enhanced long-term cell growth. The scratch assay indicated improved cell migration, and transcriptional analysis revealed significantly higher CK-18 levels in ADMSCs treated with PVA/CMC/CE 5% (p < 0.001). ICC results showed significantly higher pan-CK expression at 3.5% CE (41.82%) and 5% CE (48.16%), suggesting that CE promotes repair processes. These findings suggest that 5% CE-loaded PVA/CMC hydrogel could be an effective option for skin regeneration and antiaging.
Impact Statement
Caviar extract (CE) was considered a bioactive ingredient, along with polyvinyl alcohol (PVA) and carboxymethyl chitosan (CMC) polymers, to prepare a functional and practical hydrogel without hazardous components for anti-aging and cosmetic applications. In the present study, the PVA/CMC hydrogel contains various concentrations of CE (3.5% and 5%), is biocompatible, and enhances cellular viability and migration of adipose-derived mesenchymal stem cell. Our results demonstrated that the synergistic effect of CE and CMC could promote the expression of cytokeratin-18 gene and pan-cytokeratin protein and play a critical role in stimulating skin regeneration.
OsiAR, ZhangH, ChenJ, et al.Three-dimensional-printable thermo/photo-cross-linked methacrylated chitosan–gelatin hydrogel composites for tissue engineering. ACS Appl Mater Interfaces, 2021; 13(19):22902–22913.
2.
CostelloL, DicolandreaT, TasseffR, et al.Tissue engineering strategies to bioengineer the ageing skin phenotype in vitro. Aging Cell, 2022; 21(2):e13550; doi: 10.1111/acel.13550
3.
MakrantonakiE, ZouboulisCC. Molecular mechanisms of skin aging: State of the art. Annals of the New York Academy of Sciences, 2007; 1119(1):40–50; doi: 10.1196/annals.1404.027
4.
DC. The Design and Development of Anti-Aging Formulations. Skin Aging Handbook; 2009; 291–325, doi: 10.1016/B978-0-8155-1584-5.50016-8
5.
ResendeDI, FerreiraM, MagalhãesC, et al.Trends in the use of marine ingredients in anti-aging cosmetics. Algal Res, 2021; 55:102273.
6.
NaGH, KimS, JungHM, et al.Skin anti-aging efficacy of enzyme-treated supercritical caviar extract: A randomized, double-blind, placebo-controlled clinical trial. Nutrients, 2023; 16(1):137.
7.
UppalaL. A review on active ingredients from marine sources used in cosmetics. SOJPPS, 2015; 2(3):1–3.
8.
ParkJ, KimD, LeeM, et al.Enzyme-treated caviar prevents UVB irradiation-induced skin photoaging. Mar Drugs, 2022; 20(11):685.
9.
LeeK-E, NhoY-H, YunSK, et al.Caviar extract and its constituent DHA inhibits UVB-irradiated skin aging by inducing adiponectin production. Int J Mol Sci, 2020; 21(9):3383.
10.
ZhangH, ZhangF, YuanR. Applications of natural polymer-based hydrogels in the food industry. In: Hydrogels Based on Natural Polymers. Elsevier: 2020; pp. 357–410.
11.
StanisławM, AlinaS, AmitJ. Biopolymers for hydrogels in cosmetics. Journal of Materials Science: Materials in Medicine, 2020; 31(6).
12.
Zagórska-DziokM, SobczakM. Hydrogel-based active substance release systems for cosmetology and dermatology application: A review. Pharmaceutics, 2020; 12(5):396.
13.
ArefianM, HojjatiM, TajzadI, et al.A review of Polyvinyl alcohol/Carboxymethyl cellulose (PVA/CMC) composites for various applications. Journal of Composites and Compounds, 2020; 2(3):69–76.
14.
RajabiR, MohamadaliM, SharifiF, MoradiY, HanjaniGN, IraniS. Enhanced osteogenic differentiation for bone tissue engineering: The synergistic effect of adipose‐derived mesenchymal stem cell exosomes and Carboxymethyl chitosan hydrogel. Polymers for Advanced Techs, 2025; 36(1).
15.
KamounEA, ChenX, EldinMSM, et al.Crosslinked poly (vinyl alcohol) hydrogels for wound dressing applications: A review of remarkably blended polymers. Arab J Chem, 2015; 8(1):1–14.
16.
KenawyE-R, KamounEA, EldinMSM, et al.Physically crosslinked poly (vinyl alcohol)-hydroxyethyl starch blend hydrogel membranes: Synthesis and characterization for biomedical applications. Arab J Chem, 2014; 7(3):372–380.
17.
CovielloT, MatricardiP, MarianecciC, et al.Polysaccharide hydrogels for modified release formulations. J Control Release, 2007; 119(1):5–24.
18.
MouryaV, InamdarNN, TiwariA. Carboxymethyl chitosan and its applications. Adv Mater Lett, 2010; 1(1):11–33.
19.
ShariatiniaZ. Carboxymethyl chitosan: Properties and biomedical applications. Int J Biol Macromol, 2018; 120(Pt B):1406–1419.
20.
WangW, YuanZ, LiT, et al.Rapid preparation of highly stretchable and fast self-repairing antibacterial hydrogels for promoting hemostasis and wound healing. ACS Appl Bio Mater, 2024; 7(1):394–405.
21.
MirpourM, SiahmazgiZG, KiasaraieMS. Antibacterial activity of clove, gall nut methanolic and ethanolic extracts on Streptococcus mutans PTCC 1683 and Streptococcus salivarius PTCC 1448. J Oral Biol Craniofac Res, 2015; 5(1):7–10.
22.
SharifiF, AtyabiSM, NorouzianD, et al.Polycaprolactone/carboxymethyl chitosan nanofibrous scaffolds for bone tissue engineering application. Int J Biol Macromol, 2018; 115:243–248; doi: 10.1016/j.ijbiomac.2018.04.045
23.
Al-AlawiA, Van de VoortFR, SedmanJ. New FTIR method for the determination of FFA in oils. J Am Oil Chem Soc, 2004; 81:441–446.
24.
HashimotoT, KojimaK, TamadaY. Gene expression advances skin reconstruction and wound repair better on silk fibroin-based materials than on collagen-based materials. Materialia (Oxf), 2020; 9:100519.
25.
SharifiF, HasaniM, AtyabiSM, et al.Mesenchymal stem cells encapsulation in chitosan and carboxymethyl chitosan hydrogels to enhance osteo-differentiation. Mol Biol Rep, 2022; 49(12):12063–12075.
26.
HuZ, ChengJ, XuS, et al.PVA/pectin composite hydrogels inducing osteogenesis for bone regeneration. Mater Today Bio, 2022; 16:100431.
27.
ShenJ, BurgessDJ. Accelerated in vitro release testing of implantable PLGA microsphere/PVA hydrogel composite coatings. Int J Pharm, 2012; 422(1–2):341–348.
28.
KumarP, NagarajanA, UchilPD. Analysis of cell viability by the MTT assay. Cold Spring Harb Protoc, 2018; 2018(6); doi: 10.1101/pdb.prot095505
29.
SutirmanZA, SanagiMM, Abd KarimKJ, et al.Preparation of methacrylamide-functionalized crosslinked chitosan by free radical polymerization for the removal of lead ions. Carbohydr Polym, 2016; 151:1091–1099.
30.
MonteiroOAJr, AiroldiC. Some studies of crosslinking chitosan–glutaraldehyde interaction in a homogeneous system. Int J Biol Macromol, 1999; 26(2–3):119–128.
31.
AkbariA, RabbaniS, IraniS, et al.In vitro and in vivo study of carboxymethyl chitosan/polyvinyl alcohol for wound dressing application. J of Applied Polymer Sci, 2022; 139(10):51764.
32.
Studzińska-SrokaE, Paczkowska-WalendowskaM, ErdemC, et al.Anti-Aging properties of chitosan-based hydrogels rich in bilberry fruit extract. Antioxidants (Basel), 2024; 13(1):105.
33.
RostamiF, YekrangJ, GholamshahbaziN, et al.Under-eye patch based on PVA-gelatin nanocomposite nanofiber as a potential skin care product for fast delivery of the coenzyme Q10 anti-aging agent: In vitro and in vivo studies. Emergent Mater, 2023; 6(6):1903–1921.
34.
WangL-Y, WangM-J. Removal of heavy metal ions by poly (vinyl alcohol) and carboxymethyl cellulose composite hydrogels prepared by a freeze–thaw method. ACS Sustainable Chem Eng, 2016; 4(5):2830–2837; doi: 10.1021/acssuschemeng.6b00336
35.
CanillasM, de LimaGG, RodríguezMA, NugentMJD, DevineDM. Bioactive composites fabricated by freezing‐thawing method for bone regeneration applications. J Polym Sci Part B: Polym Phys, 2016; 54(7):761–773.
36.
Bernal-ChávezSA, Romero-MonteroA, Hernández-ParraH, et al.Enhancing chemical and physical stability of pharmaceuticals using freeze-thaw method: Challenges and opportunities for process optimization through quality by design approach. J Biol Eng, 2023; 17(1):35.
37.
OliveiraRN, MeleiroL, QuiltyB, et al.Release of natural extracts from PVA and PVA-CMC hydrogel wound dressings: A power law swelling/delivery. Front Bioeng Biotechnol, 2024; 12:1406336; doi: 10.3389/fbioe.2024.1406336
38.
El SalmawiKM. Application of polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC) hydrogel produced by conventional crosslinking or by freezing and thawing. Journal of Macromolecular Science, Part A: Pure and Applied Chemistry, 2007; 44(6):619–624.
39.
LotfipourF, Alami-MilaniM, SalatinS, et al.Freeze-thaw-induced cross-linked PVA/chitosan for oxytetracycline-loaded wound dressing: The experimental design and optimization. Res Pharm Sci, 2019; 14(2):175–189.
40.
TyagiV, ThakurA. Carboxymethyl cellulose-polyvinyl alcohol based materials: A review. Materials Today: Proceedings, 2023.
41.
OlevskyLM, JacquesMG, HixonKR. PoreVision: A program for enhancing efficiency and accuracy in SEM pore analyses of gels and other porous materials. Gels, 2025; 11(2):132.
42.
JayawardenaI, TurunenP, GarmsBC, et al.Evaluation of techniques used for visualisation of hydrogel morphology and determination of pore size distributions. Mater Adv, 2023; 4(2):669–682.
43.
GeahchanS, BaharloueiP, RahmanA. Marine collagen: A promising biomaterial for wound healing, skin anti-aging, and bone regeneration. Mar Drugs, 2022; 20(1):61.
44.
LutzweilerG, Ndreu HaliliA, Engin VranaN. The overview of porous, bioactive scaffolds as instructive biomaterials for tissue regeneration and their clinical translation. Pharmaceutics, 2020; 12(7):602.
45.
PinthongT, YooyodM, DaengmankhongJ, et al.Development of natural active agent-containing porous hydrogel sheets with high water content for wound dressings. Gels, 2023; 9(6):459; doi: 10.3390/gels9060459
46.
AlinaTB, NashVA, SpillerKL. Effects of biotin-avidin interactions on hydrogel swelling. Front Chem, 2020; 8:593422.
47.
WirthM, KirschbaumF, GessnerJ, et al.Fatty acid composition in sturgeon caviar from different species: Comparing wild and farmed origins. Internat Rev Hydrobiol, 2002; 87(5–6)‐:629–636.
48.
MansurHS, OréficeRL, MansurAA. Characterization of poly (vinyl alcohol)/poly (ethylene glycol) hydrogels and PVA-derived hybrids by small-angle X-ray scattering and FTIR spectroscopy. Polymer (Guildf), 2004; 45(21):7193–7202.
49.
EzeFN, JayeoyeTJ, EzeRC, et al.Construction of carboxymethyl chitosan/PVA/chitin nanowhiskers multicomponent film activated with Cotylelobium lanceolatum phenolics and in situ SeNP for enhanced packaging application. Int J Biol Macromol, 2024; 255:128073.
50.
JenningV, Schäfer-KortingM, GohlaS. Vitamin A-loaded solid lipid nanoparticles for topical use: Drug release properties. J Control Release, 2000; 66(2–3):115–126.
51.
PrausnitzMR, LangerR. Transdermal drug delivery. Nat Biotechnol, 2008; 26(11):1261–1268.
52.
PeppasNA, BuresP, LeobandungW, et al.Hydrogels in pharmaceutical formulations. Eur J Pharm Biopharm, 2000; 50(1):27–46.
53.
SolbuAA, CaballeroD, DamigosS, et al.Assessing cell migration in hydrogels: An overview of relevant materials and methods. Mater Today Bio, 2023; 18:100537.
54.
ChenX, ZhangM, ChenS, et al.Peptide-modified chitosan hydrogels accelerate skin wound healing by promoting fibroblast proliferation, migration, and secretion. Cell Transplant, 2017; 26(8):1331–1340.
55.
ZhangL-J. Keratins in skin epidermal development and diseases. In: Keratin. IntechOpen; 2018.
56.
KasowanjeteP, KumarSSD, HoureldNN. A review of photobiomodulation on PI3K/AKT/mTOR in wound healing. J Photochem Photobiol, 2024; 19:100215.
57.
TengY, FanY, MaJ, et al.The PI3K/Akt pathway: Emerging roles in skin homeostasis and a group of non-malignant skin disorders. Cells, 2021; 10(5):1219; doi: 10.3390/cells10051219
58.
ZhangLJ. Keratins in Skin Epidermal Development and Diseases. InTech Open; 2018.
59.
PankowS, BambergerC, KlippelA, et al.Regulation of epidermal homeostasis and repair by phosphoinositide 3-kinase. J Cell Sci, 2006; 119(Pt 19):4033–4046.
60.
RoyT, BoatengST, UddinMB, et al.The PI3K-Akt-mTOR and associated signaling pathways as molecular drivers of immune-mediated inflammatory skin diseases: Update on therapeutic strategy using natural and synthetic compounds. Cells, 2023; 12(12):1671.
61.
KararJ, MaityA. PI3K/AKT/mTOR pathway in angiogenesis. Front Mol Neurosci, 2011; 4:51.
62.
WuT, ZhangYM, KrishnanS, et al.Bioactive small molecule enhances skin burn wound healing and hair follicle regeneration by activating PI3K/AKT signaling pathway: A preclinical evaluation in animal model. J Biomed Nanotechnol, 2022; 18(2):463–473.
63.
ChenQ, ZhangH, YangY, et al.Metformin attenuates UVA-induced skin photoaging by suppressing mitophagy and the PI3K/AKT/mTOR pathway. Int J Mol Sci, 2022; 23(13):6960.
64.
SunJ, ZhaoH, ShenC, et al.Tideglusib promotes wound healing in aged skin by activating PI3K/Akt pathway. Stem Cell Res Ther, 2022; 13(1):269.
65.
HeX, WanF, SuW, et al.Research progress on skin aging and active ingredients. Molecules, 2023; 28(14):5556.
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