{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:37:17Z","timestamp":1781743037438,"version":"3.54.5"},"reference-count":51,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,9]],"date-time":"2024-11-09T00:00:00Z","timestamp":1731110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Polyvinyl alcohol (PVA), possessing a strong ability to form hydrogels, has been widely used for various pharmaceutical and biomedical applications. In particular, the use of PVA-PEG in the form of theta gels for altered cartilage treatment has attracted an enormous amount of attention in the last 20 years. In this paper, we prepared 42 PVA-PEG in the form of theta gels at room temperature in an aqueous environment, testing the crystallization occurrence at basic pH (10 or 12). Using a statistical approach, the effect of PEG molecular weight, PVA molecular weight and alkaline pH values on water content and mechanical performance was evaluated. The used procedure permitted the theta gels to maintain swelling properties comparable to those of human cartilage, from 60% to 85%, with both polymers having the same influence. PEG MW mainly affected the hydrophilic properties, whereas the thermal properties were mostly influenced by the PVA. The shear and compression mechanical behavior of the produced materials were affected by both the polymers\u2019 MWs. The sample obtained using PVA 125 kDa with PEG 20 kDa as a porogen appeared to be the most suitable one for cartilage disease treatment, as it had an equilibrium shear modulus in the range of 50\u2013250 kPa, close to that of native articular cartilage, as well as optimal mechanical response under compression along the entire analyzed frequency range with a mean value of 0.12 MPa and a coefficient of friction (COF) which remained under 0.10 for all the tested sliding speeds (mm\/s).<\/jats:p>","DOI":"10.3390\/ijms252212039","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T03:52:07Z","timestamp":1731297127000},"page":"12039","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effect of Mild Conditions on PVA-Based Theta Gel Preparation: Thermal and Rheological Characterization"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3290-9644","authenticated-orcid":false,"given":"Simone","family":"Pepi","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro 2, 53100 Siena, Italy"},{"name":"National Interuniversity Consortium of Materials Science and Technology (INSTM), Via G. Giusti 9, 50121 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Talarico","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro 2, 53100 Siena, Italy"},{"name":"National Interuniversity Consortium of Materials Science and Technology (INSTM), Via G. Giusti 9, 50121 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0820-6068","authenticated-orcid":false,"given":"Gemma","family":"Leone","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro 2, 53100 Siena, Italy"},{"name":"National Interuniversity Consortium of Materials Science and Technology (INSTM), Via G. Giusti 9, 50121 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4328-3253","authenticated-orcid":false,"given":"Claudia","family":"Bonechi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro 2, 53100 Siena, Italy"},{"name":"Centre for Colloid and Surface Science (CSGI), Via della Lastruccia 3, Sesto Fiorentino (FI), 50019 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7516-9105","authenticated-orcid":false,"given":"Marco","family":"Consumi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro 2, 53100 Siena, Italy"},{"name":"National Interuniversity Consortium of Materials Science and Technology (INSTM), Via G. Giusti 9, 50121 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8253-7371","authenticated-orcid":false,"given":"Amedeo","family":"Boldrini","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro 2, 53100 Siena, Italy"},{"name":"Centre for Colloid and Surface Science (CSGI), Via della Lastruccia 3, Sesto Fiorentino (FI), 50019 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Lauro","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6960-9418","authenticated-orcid":false,"given":"Agnese","family":"Magnani","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro 2, 53100 Siena, Italy"},{"name":"National Interuniversity Consortium of Materials Science and Technology (INSTM), Via G. Giusti 9, 50121 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6032-1015","authenticated-orcid":false,"given":"Claudio","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro 2, 53100 Siena, Italy"},{"name":"Centre for Colloid and Surface Science (CSGI), Via della Lastruccia 3, Sesto Fiorentino (FI), 50019 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,9]]},"reference":[{"key":"ref_1","first-page":"674","article-title":"A review of polyvinyl alcohol derivatives: Promising materials for pharmaceutical and biomedical apllications","volume":"8","author":"Marin","year":"2014","journal-title":"Afr. J. Pharm. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/3-540-46414-X_2","article-title":"Structure and applications of poly (vinyl alcohol) hydrogels produced by conventional crosslinking or by freezing\/thawing methods","volume":"Volume 153","author":"Hassan","year":"2000","journal-title":"Biopolymers PVA Hydrogels, Anionic Polymerisation Nanocomposites. Advances in Polymer Science"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Chen, Y., Song, J., Wang, S., and Liu, W. (2021). PVA-Based Hydrogels: Promising Candidates for Articular Cartilage Repair. Macromol. Biosci., 21.","DOI":"10.1002\/mabi.202170028"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/S0141-3910(98)00206-7","article-title":"Biodegradation of poly (vinyl alcohol) based blown films under different environmental conditions","volume":"64","author":"Chiellini","year":"1999","journal-title":"Polym. Degrad. Stab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.jconrel.2016.10.032","article-title":"pH-degradable PVA-based nanogels via photo-crosslinking of thermo-preinduced nanoaggregates for controlled drug delivery","volume":"259","author":"Chen","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.jddst.2019.05.037","article-title":"Design and 3D printing of multi-compartmental PVA capsules for drug delivery","volume":"52","author":"Poropat","year":"2019","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kumar, A., and Han, S.S. (2017). PVA-based hydrogels for tissue engineering: A review. Int. J. Polym. Mater. Polym. Biomater., 66.","DOI":"10.1080\/00914037.2016.1190930"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"133790","DOI":"10.1016\/j.colsurfa.2024.133790","article-title":"Superparamagnetic freeze-thawed PVA hydrogel for applications in tissue engineering, drug delivery and bioimaging","volume":"690","author":"Murugan","year":"2024","journal-title":"Colloids Surf. A: Physicochem. Eng. Asp."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/j.msec.2015.10.052","article-title":"An evaluation of the biocompatibility properties of a salt-modified polyvinyl alcohol hydrogel for a knee meniscus application","volume":"59","author":"Hayes","year":"2016","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.jare.2017.01.005","article-title":"A review on polymeric hydrogel membranes for wound dressing applications: PVA-based hydrogel dressings","volume":"8","author":"Elbadawy","year":"2017","journal-title":"J. Adv. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1002\/jbm.b.32694","article-title":"A review of polyvinyl alcohol and its uses in cartilage and orthopedic applications","volume":"100B","author":"Baker","year":"2012","journal-title":"J. Biomed. Mater. Res. Part B"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.bsbt.2016.02.002","article-title":"Frictional properties of physically cross-linked PVA hydrogels as artificial cartilage","volume":"2","author":"Sasaki","year":"2016","journal-title":"Biosurface Biotribology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1016\/j.jmrt.2023.03.130","article-title":"Recent advances of PVA-based hydrogels in cartilage repair application","volume":"24","author":"Li","year":"2023","journal-title":"J. Mater. Res. Technol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"113048","DOI":"10.1016\/j.matdes.2024.113048","article-title":"Physically crosslinked poly(vinyl alcohol)-based hydrogels for cartilage tissue engineering","volume":"243","author":"Xiang","year":"2024","journal-title":"Mater. Des."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.jmrt.2022.12.166","article-title":"Biodegradable glass fiber reinforced PVA hydrogel for cartilage repair: Mechanical properties, ions release behavior and cell recruitment","volume":"23","author":"Zhu","year":"2023","journal-title":"J. Mater. Res. Technol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.matpr.2019.03.214","article-title":"Synthesis and characterization of electrospinning PVA nanofiber-crosslinked by glutaraldehyde","volume":"13","author":"Hulupi","year":"2019","journal-title":"Mater. Today Proc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7293","DOI":"10.1016\/j.tet.2016.02.017","article-title":"Boronic acids as efficient cross linkers for PVA: Synthesis and application of tunable hollow microspheres in biocatalysis","volume":"72","author":"Nunes","year":"2016","journal-title":"Tetrahedron"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1002\/pat.3150","article-title":"States of water, surface and rheological characterisation of a new biohydrogel as articular cartilage substitute","volume":"24","author":"Leone","year":"2013","journal-title":"Polym. Adv. Technol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1002\/jbm.a.35389","article-title":"Continuous multilayered composite hydrogel as osteochondral substitute","volume":"103","author":"Leone","year":"2014","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.matchemphys.2018.05.038","article-title":"Kinetics and thermodynamics of swelling and dissolution of PVA gels obtained by freeze-thaw technique","volume":"216","author":"Agudelo","year":"2018","journal-title":"Mater. Chem. Phys."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"110974","DOI":"10.1016\/j.eurpolymj.2021.110974","article-title":"Freeze\/thawed polyvinyl alcohol hydrogels: Present, past and future","volume":"164","author":"Adelnia","year":"2022","journal-title":"Eur. Polym. J."},{"key":"ref_22","unstructured":"Ruberti, J.W., and Braithwaite, G.J.C. (2004). Systems and methods for controlling and forming polymer gels. (20040092653), U.S. Patent."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.jmbbm.2019.01.002","article-title":"PVA-gelatin hydrogels formed using combined theta-gel and cryo-gel fabrication techniques","volume":"92","author":"Charron","year":"2019","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.biomaterials.2007.09.015","article-title":"The effect of polyethylene glycol on the stability of pores in polyvinyl alcohol hydrogels during annealing","volume":"29","author":"Choi","year":"2008","journal-title":"Biomaterials"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Charron, P.N., Blatt, S.E., McKenzie, C., and Oldinski, R.A. (2017). Dynamic mechanical response of polyvinyl alcohol-gelatin theta-gels for nucleus pulposus tissue replacement. Biointerphases, 12.","DOI":"10.1116\/1.4982643"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Virdi, C., Lu, Z., Zreiqat, H., and No, Y.J. (2023). Theta-Gel-Reinforced Hydrogel Composites for Potential Tensile Load-Bearing Soft Tissue Repair Applications. J. Funct. Biomater., 14.","DOI":"10.3390\/jfb14060291"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"48706","DOI":"10.1002\/app.48706","article-title":"Crystallinity, reversibility, and injectability of physically crosslinked poly(vinyl alcohol) and poly(ethylene glycol) hydrogels","volume":"137","author":"LaMastro","year":"2020","journal-title":"J. Appl. Polym. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1007\/s40242-017-7107-9","article-title":"PVA\/PEG hybrid hydrogels prepared by freeze-thawing and high energy electron beam irradiation","volume":"33","author":"Chunming","year":"2017","journal-title":"Chem. Res. Chin. Univ."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e51563","DOI":"10.1002\/app.51563","article-title":"Double-network polyvinyl alcohol composite hydrogel with self-healing and low friction","volume":"139","author":"Zhang","year":"2022","journal-title":"J. Appl. Polym. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3455","DOI":"10.1002\/pat.5799","article-title":"Organic solvents enhance polyvinyl alcohol\/polyethylene glycol self-healing hydrogels for artificial cartilage","volume":"33","author":"Ye","year":"2022","journal-title":"Polym. Adv. Technol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Liu, P., Chen, W., Liu, C., Ming Tian, M., and Liu, P. (2019). A novel poly (vinyl alcohol)\/poly (ethylene glycol) scaffold for tissue engineering with a unique bimodal open-celled structure fabricated using supercritical fluid foaming. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-46061-7"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2890","DOI":"10.1002\/app.36223","article-title":"Molecular Weight Effect on Theta-Gel Formation in Poly(vinyl alcohol)\u2013Poly(ethylene glycol) Mixtures","volume":"125","author":"Oral","year":"2012","journal-title":"J. Appl. Polym. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7777","DOI":"10.1038\/s41467-024-52264-y","article-title":"Control nucleation for strong and tough crystalline hydrogels with high water content","volume":"15","author":"Huang","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1902740","DOI":"10.1002\/advs.201902740","article-title":"An Alkaline Based Method for Generating Crystalline, Strong, and Shape Memory Polyvinyl Alcohol Biomaterials","volume":"7","author":"Darabi","year":"2020","journal-title":"Adv. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Barbucci, R. (2002). Articular Cartilage. Integrated Biomaterials Science, Kluwer Academic\/Plenum Publishers.","DOI":"10.1007\/b112196"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.actbio.2015.09.034","article-title":"The structure and mechanical properties of articular cartilage are highly resilient towards transient dehydration","volume":"29","author":"Boettcher","year":"2016","journal-title":"Acta Biomater."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1080\/00914037.2020.1848831","article-title":"Calcium ions hyaluronan\/gellan gum protective shell for delivery of oleuropein in the knee","volume":"71","author":"Consumi","year":"2022","journal-title":"Int. J. Polym. Mater. Polym. Biomater."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"118452","DOI":"10.1016\/j.carbpol.2021.118452","article-title":"Sodium hyaluronate-g-2-((N-(6-aminohexyl)-4-methoxyphenyl)sulfonamido)-N-hydroxyacetamide with enhanced affinity towards MMP12 catalytic domain to be used as visco-supplement with increased degradation resistance","volume":"271","author":"Leone","year":"2021","journal-title":"Carbohydr. Polym."},{"key":"ref_39","unstructured":"Tanzi, M.C., and Far\u00e8, S. (2017). Rheometry of polymeric biomaterials. Characterization of Polymeric Biomaterials, Woodhead Publishing."},{"key":"ref_40","unstructured":"Mezger, T.G. (2014). The Rheology Handbook, Vincentz Network. [4th ed.]."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.joca.2016.11.009","article-title":"Low-energy impact of human cartilage: Predictors for microcracking the network of collagen","volume":"25","author":"Kaleem","year":"2017","journal-title":"Osteoarthr. Cartil."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1016\/j.biomaterials.2006.09.049","article-title":"Effects of solvent dehydration on creep resistance of poly(vinyl alcohol) hydrogel","volume":"28","author":"Choi","year":"2007","journal-title":"Biomaterials"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Dehghan-Baniani, D., Chen, Y., Wang, D., Bagheri, R., Solouk, A., and Wu, H. (2022). Injectable in situ forming kartogenin-loaded chitosan hydrogel with tunable rheological properties for cartilage tissue engineering. Colloids Surf. B Biointerface, 192.","DOI":"10.1016\/j.colsurfb.2020.111059"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1136\/bmj.1.5176.821","article-title":"Surgery of the Hip-joint","volume":"1","author":"Charnley","year":"1960","journal-title":"Br. Med. J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/S1672-6529(14)60137-2","article-title":"Effect of rotational and sliding motions on friction and degeneration of articular cartilage under dry and wet friction","volume":"12","author":"Cilingir","year":"2015","journal-title":"J. Bionic Eng."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.orthres.2003.07.002","article-title":"Experimental verification of the role of interstitial fluid pressurization in cartilage lubrication","volume":"22","author":"Krishnan","year":"2004","journal-title":"J. Orthop. Res."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Mahmood, H., Eckold, D., Stead, I., Shepherd, D.E., Espino, D.M., and Dearn, K.D. (2020). A method for the assessment of the coefficient of friction of articular cartilage and a replacement biomaterial. J. Mech. Behav. Biomed. Mater., 103.","DOI":"10.1016\/j.jmbbm.2019.103580"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"101708","DOI":"10.1016\/j.cocis.2023.101708","article-title":"Progress in the design and synthesis of viscosupplements for articular joint lubrication","volume":"66","author":"Gonzales","year":"2023","journal-title":"Curr. Opin. Colloid Interface Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"109328","DOI":"10.1016\/j.triboint.2024.109328","article-title":"A 3D printed biomimetic scaffold for cartilage regeneration with lubrication, load-bearing, and adhesive fixation properties","volume":"192","author":"Wei","year":"2024","journal-title":"Tribol. Int."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"204017","DOI":"10.1016\/j.wear.2021.204017","article-title":"Tribological assessments of bilayer titanium nanocomposite hydrogels for cartilage replacement in articular joints","volume":"484\u2013485","author":"Mostakhdemin","year":"2021","journal-title":"Wear"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jddst.2016.10.001","article-title":"New formulations to enhance lovastatin release from red yeast rice (RYR)","volume":"36","author":"Leone","year":"2016","journal-title":"J. Drug Deliv. Sci. 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