Tailoring the Degradation Time of Polycationic PEG-Based Hydrogels toward Dynamic Cell Culture Matrices
Open accessAbstract
High Resolution Image Download MS PowerPoint Slide Poly(ethylene glycol)-based (PEG) hydrogels provide an ideal platform to obtain well-defined and tailor-made cell culture matrices to enhance in vitro cell culture conditions, although cell adhesion is often challenging when the cells are cultivated on the substrate surface. We herein demonstrate two approaches for the synthesis of polycationic PEG-based hydrogels which were modified to enhance cell-matrix interactions, to improve two-dimensional (2D) cell culture, and catalyze hydrolytic degradation. While the utilization of N, N -(bisacryloxyethyl) amine (BAA) as cross-linker for in situ gelation provides degradable scaffolds for dynamic cell culture, the incorporation of short segments of poly( N -(3-(dimethylamino)propyl)acrylamide) (PDMAPAam) provides high local cationic charge density leading to PEG-based hydrogels with high selectivity for fibroblastic cell lines. The adsorption of transforming growth factor (TGF-β) into the hydrogels induced stimulation of fibrosis and thus the formation of collagen as a natural ECM compound. With this, these dynamic hydrogels enhance in vitro cell culture by providing a well-defined, artificial, and degradable matrix that stimulates cells to produce their own natural scaffold within a defined time frame.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
PEG derivatives such as PEG-diacrylate or PEG-polyesters have been developed to enhance mechanical stability and control degradation rates for optimized anti-adhesion applications.
“In response, PEG derivatives, such as PEG–diacrylate or PEG–polyesters, have been developed to enhance mechanical stability and control degradation rates for optimized anti-adhesion applications [220,221,222].”
From Biomaterials in Postoperative Adhesion Barriers and Uterine Tissue Engineering (2025) · cites this paper as [221]
The Degradation Kinetics section reports that changing the cross-linker composition controls degradation time and initial stiffness, and uses PEG-diacrylate as a nondegradable comparator. But the Introduction says these hydrogels were designed to improve cell adhesion for cell culture, not for anti-adhesion applications; the cited passages also do not identify PEG-polyesters as part of this approach. Page numbers are unavailable in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
No references could be resolved yet.
Research works printed but not linked: 45
- Boateng J. S.; Pawar H. V.; Tetteh J. Polyox and carrageenan based composite film dressing containing anti-microbial and anti-inflammatory drugs for effective wound healing. Int. J. Pharm. 2013, 441 (1–2), 181– 191. 10.1016/j.ijpharm.2012.11.045. 23228898 · DOI
- Liang Y.; He J.; Guo B. Functional Hydrogels as Wound Dressing to Enhance Wound Healing. ACS Nano 2021, 15 (8), 12687– 12722. 10.1021/acsnano.1c04206. 34374515 · DOI · Paper page
- Leach D. G.; Dharmaraj N.; Piotrowski S. L.; Lopez-Silva T. L.; Lei Y. L.; Sikora A. G.; Young S.; Hartgerink J. D. STINGel: Controlled release of a cyclic dinucleotide for enhanced cancer immunotherapy. Biomaterials 2018, 163, 67– 75. 10.1016/j.biomaterials.2018.01.035. 29454236 PMC5840037 · DOI
- Schoener C. A.; Hutson H. N.; Peppas N. A. pH-responsive hydrogels with dispersed hydrophobic nanoparticles for the oral delivery of chemotherapeutics. J. Biomed. Mater. Res., Part A 2013, 101A (8), 2229– 2236. 10.1002/jbm.a.34532. PMC3619027 23281185 · DOI
- Chwalek K.; Levental K. R.; Tsurkan M. V.; Zieris A.; Freudenberg U.; Werner C. Two-tier hydrogel degradation to boost endothelial cell morphogenesis. Biomaterials 2011, 32 (36), 9649– 9657. 10.1016/j.biomaterials.2011.08.078. 21937106 · DOI
- Fairbanks B. D.; Schwartz M. P.; Halevi A. E.; Nuttelman C. R.; Bowman C. N.; Anseth K. S. A Versatile Synthetic Extracellular Matrix Mimic via Thiol-Norbornene Photopolymerization. Adv. Mater. 2009, 21 (48), 5005– 5010. 10.1002/adma.200901808. 25377720 PMC4226179 · DOI
- Mantha S.; Pillai S.; Khayambashi P.; Upadhyay A.; Zhang Y.; Tao O.; Pham H. M.; Tran S. D. Smart Hydrogels in Tissue Engineering and Regenerative Medicine. Materials 2019, 12 (20), 3323 10.3390/ma12203323. 31614735 PMC6829293 · DOI
- Tibbitt M. W.; Anseth K. S. Hydrogels as extracellular matrix mimics for 3D cell culture. Biotechnol. Bioeng. 2009, 103 (4), 655– 663. 10.1002/bit.22361. 19472329 PMC2997742 · DOI · Paper page
- Girotti A.; Reguera J.; Rodríguez-Cabello J. C.; Arias F. J.; Alonso M.; Matestera A. Design and bioproduction of a recombinant multi(bio)functional elastin-like protein polymer containing cell adhesion sequences for tissue engineering purposes. J. Mater. Sci. Mater. Med. 2004, 15 (4), 479– 484. 10.1023/b:jmsm.0000021124.58688.7a. 15332621 · DOI
- Hern D. L.; Hubbell J. A. Incorporation of adhesion peptides into nonadhesive hydrogels useful for tissue resurfacing. J. Biomed Mater. Res. 1998, 39 (2), 266– 276. 10.1002/(SICI)1097-4636(199802)39:2<266::AID-JBM14>3.0.CO;2-B. 9457557 · DOI · Paper page
- Plow E. F.; Haas T. A.; Zhang L.; Loftus J.; Smith J. W. Ligand Binding to Integrins*. J. Biol. Chem. 2000, 275 (29), 21785– 21788. 10.1074/jbc.R000003200. 10801897 · DOI
- Fittkau M. H.; Zilla P.; Bezuidenhout D.; Lutolf M. P.; Human P.; Hubbell J. A.; Davies N. The selective modulation of endothelial cell mobility on RGD peptide containing surfaces by YIGSR peptides. Biomaterials 2005, 26 (2), 167– 174. 10.1016/j.biomaterials.2004.02.012. 15207463 · DOI
- Lutolf M. P.; Weber F. E.; Schmoekel H. G.; Schense J. C.; Kohler T.; Müller R.; Hubbell J. A. Repair of bone defects using synthetic mimetics of collagenous extracellular matrices. Nat. Biotechnol. 2003, 21 (5), 513– 518. 10.1038/nbt818. 12704396 · DOI · Paper page
- Burdick J. A.; Anseth K. S. Photoencapsulation of osteoblasts in injectable RGD-modified PEG hydrogels for bone tissue engineering. Biomaterials 2002, 23 (22), 4315– 4323. 10.1016/S0142-9612(02)00176-X. 12219821 · DOI · Paper page
- Mann B. K.; Gobin A. S.; Tsai A. T.; Schmedlen R. H.; West J. L. Smooth muscle cell growth in photopolymerized hydrogels with cell adhesive and proteolytically degradable domains: synthetic ECM analogs for tissue engineering. Biomaterials 2001, 22 (22), 3045– 3051. 10.1016/S0142-9612(01)00051-5. 11575479 · DOI
- Liu D.; Wang T.; Liu X.; Tong Z. Cell proliferation and cell sheet detachment from the positively and negatively charged nanocomposite hydrogels. Biopolymers 2014, 101 (1), 58– 65. 10.1002/bip.22273. 23640767 · DOI
- Yavin E.; Yavin Z. Attachment and culture of dissociated cells from rat embryo cerebral hemispheres on polylysine-coated surface. J. Cell Biol. 1974, 62 (2), 540 10.1083/jcb.62.2.540. 4609989 PMC2109386 · DOI
- Cai L.; Lu J.; Sheen V.; Wang S. Promoting Nerve Cell Functions on Hydrogels Grafted with Poly(l-lysine). Biomacromolecules 2012, 13 (2), 342– 349. 10.1021/bm201763n. 22251248 PMC3538025 · DOI
- Zou Y.-J.; He S.-S.; Du J.-Z. ε-Poly(L-lysine)-based Hydrogels with Fast-acting and Prolonged Antibacterial Activities. Chin J. Polym. Sci. 2018, 36 (11), 1239– 1250. 10.1007/s10118-018-2156-1. · DOI
- Pätzold F.; Stamm N.; Kamps D.; Specht M.; Bolduan P.; Dehmelt L.; Weberskirch R. Synthesis and Characterization of Cationic Hydrogels from Thiolated Copolymers for Independent Manipulation of Mechanical and Chemical Properties of Cell Substrates. Macromol. Biosci 2022, 22 (5), 2100453 10.1002/mabi.202100453. 35152564 · DOI
- Kroupová J.; Horák D.; Pacherník J.; Dvořák P.; Šlouf M. Functional polymer hydrogels for embryonic stem cell support. J. Biomed Mater. Res, Part B 2006, 76B (2), 315– 325. 10.1002/jbm.b.30366. 16080172 · DOI
- Shen Z.; Mellati A.; Bi J.; Zhang H.; Dai S. A thermally responsive cationic nanogel-based platform for three-dimensional cell culture and recovery. RSC Adv. 2014, 4 (55), 29146– 29156. 10.1039/C4RA02852J 10.1039/C4RA02852J. · DOI
- Alge D. L.; Azagarsamy M. A.; Donohue D. F.; Anseth K. S. Synthetically Tractable Click Hydrogels for Three-Dimensional Cell Culture Formed Using Tetrazine–Norbornene Chemistry. Biomacromolecules 2013, 14 (4), 949– 953. 10.1021/bm4000508. 23448682 PMC3623454 · DOI
- Chaudhuri O.; Gu L.; Darnell M.; Klumpers D.; Bencherif S. A.; Weaver J. C.; Huebsch N.; Mooney D. J. Substrate stress relaxation regulates cell spreading. Nat. Commun. 2015, 6 (1), 6365 10.1038/ncomms7365. PMC4518451 25695512 · DOI
- Sridhar B. V.; Brock J. L.; Silver J. S.; Leight J. L.; Randolph M. A.; Anseth K. S. Development of a Cellularly Degradable PEG Hydrogel to Promote Articular Cartilage Extracellular Matrix Deposition. Adv. Healthcare Mater. 2015, 4 (5), 702– 713. 10.1002/adhm.201400695. PMC4487633 25607633 · DOI
- Zhao W.; Jin X.; Cong Y.; Liu Y.; Fu J. Degradable natural polymer hydrogels for articular cartilage tissue engineering. J. Appl. Chem. Biotechnol 2013, 88 (3), 327– 339. 10.1002/jctb.3970. · DOI
- Lutolf M. P.; Lauer-Fields J. L.; Schmoekel H. G.; Metters A. T.; Weber F. E.; Fields G. B.; Hubbell J. A. Synthetic matrix metalloproteinase-sensitive hydrogels for the conduction of tissue regeneration: Engineering cell-invasion characteristics. Proc. Natl. Acad. Sci. U.S.A. 2003, 100 (9), 5413– 5418. 10.1073/pnas.0737381100. 12686696 PMC154359 · DOI · Paper page
- Turturro M. V.; Christenson M. C.; Larson J. C.; Young D. A.; Brey E. M.; Papavasiliou G. MMP-Sensitive PEG Diacrylate Hydrogels with Spatial Variations in Matrix Properties Stimulate Directional Vascular Sprout Formation. PLoS One 2013, 8 (3), e58897 10.1371/journal.pone.0058897. 23554954 PMC3595229 · DOI
- Lutolf M. P.; Raeber G. P.; Zisch A. H.; Tirelli N.; Hubbell J. A. Cell-Responsive Synthetic Hydrogels. Adv. Mater. 2003, 15 (11), 888– 892. 10.1002/adma.200304621. · DOI
- Hao Y.; Shih H.; Munoz Z.; Kemp A.; Lin C. C. Visible light cured thiol-vinyl hydrogels with tunable degradation for 3D cell culture. Acta Biomater. 2014, 10 (1), 104– 114. 10.1016/j.actbio.2013.08.044. 24021231 PMC3840055 · DOI
- Lin C.-C.; Ki C. S.; Shih H. Thiol–norbornene photoclick hydrogels for tissue engineering applications. J. Appl. Polym. Sci. 2015, 132 (8), 41563 10.1002/app.41563. 25558088 PMC4280501 · DOI
- Lutolf M. P.; Tirelli N.; Cerritelli S.; Cavalli L.; Hubbell J. A. Systematic Modulation of Michael-Type Reactivity of Thiols through the Use of Charged Amino Acids. Bioconjugate Chem. 2001, 12 (6), 1051– 1056. 10.1021/bc015519e. 11716699 · DOI
- Tehrani-Bagha A.; Holmberg K. Cleavable surfactants. Curr. Opin. Colloid Interface Sci. 2007, 12 (2), 81– 91. 10.1016/j.cocis.2007.05.006. · DOI
- Yom-Tov O.; Seliktar D.; Bianco-Peled H. PEG-Thiol based hydrogels with controllable properties. Eur. Polym. J. 2016, 74, 1– 12. 10.1016/j.eurpolymj.2015.11.002. · DOI
- Kowalczuk K.; Dasgupta A.; Páez Larios F.; Ulrich H. F.; Wegner V.; Brendel J. C.; Eggeling C.; Mosig A. S.; Schacher F. H. Self-Degrading Multifunctional PEG-Based Hydrogels—Tailormade Substrates for Cell Culture. Macromol. Biosci. 2024, 2300383 10.1002/mabi.202300383. 38102978 · DOI
- Kowalczuk K.; Mons P. J.; Ulrich H. F.; Wegner V. D.; Brendel J. C.; Mosig A. S.; Schacher F. H. Asymmetric Block Extension of Star-Shaped [PEG-SH](4) - toward Poly(dehydroalanine)-Functionalized PEG Hydrogels for Catch and Release of Charged Guest Molecules. Macromol. Biosci. 2024, 24, 2300230 10.1002/mabi.202300230. 37572335 · DOI
- Brady S. R.; Gohsman S. B.; Sepulveda K.; Weaver J. D. Engineering synthetic poly (ethylene) glycol-based hydrogels compatible with injection molding biofabrication. J. Biomed Mater. Res, Part A 2023, 111 (6), 814– 824. 10.1002/jbm.a.37523. 36866410 · DOI
- Guarnieri D.; De Capua A.; Ventre M.; Borzacchiello A.; Pedone C.; Marasco D.; Ruvo M.; Netti P. A. Covalently immobilized RGD gradient on PEG hydrogel scaffold influences cell migration parameters. Acta Biomater 2010, 6 (7), 2532– 2539. 10.1016/j.actbio.2009.12.050. 20051270 · DOI
- Xun M.-M.; Huang Z.; Xiao Y.-P.; Liu Y.-H.; Zhang J.; Zhang J.-H.; Yu X.-Q. Synthesis and Properties of Low-Molecular-Weight PEI-Based Lipopolymers for Delivery of DNA. Polymers 2018, 10 (10), 1060 10.3390/polym10101060. 30960985 PMC6403936 · DOI
- Xun M.-M.; Xiao Y.-P.; Zhang J.; Liu Y.-H.; Peng Q.; Guo Q.; Wu W.-X.; Xu Y.; Yu X.-Q. Low molecular weight PEI-based polycationic gene vectors via Michael addition polymerization with improved serum-tolerance. Polymer 2015, 65, 45– 54. 10.1016/j.polymer.2015.03.070. · DOI
- Ezell R. G.; Lowe A. B.; McCormick C. L. Synthetic Polyzwitterions: Water-Soluble Copolymers and Terpolymers. In Polyelectrolytes and Polyzwitterions; ACS Symposium Series, 2006; Vol. 937, pp 47– 63.
- Xu L.; Hui A. Y.; Albanis E.; Arthur M. J.; O’Byrne S. M.; Blaner W. S.; Mukherjee P.; Friedman S. L.; Eng F. J. Human hepatic stellate cell lines, LX-1 and LX-2: new tools for analysis of hepatic fibrosis. Gut 2005, 54 (1), 142– 151. 10.1136/gut.2004.042127. 15591520 PMC1774377 · DOI
- Xu L.-P.; Meng J.; Zhang S.; Ma X.; Wang S. Amplified effect of surface charge on cell adhesion by nanostructures. Nanoscale 2016, 8 (25), 12540– 12543. 10.1039/C6NR00649C. 27150434 · DOI
- Zhong X.; Rescorla F. J. Cell surface adhesion molecules and adhesion-initiated signaling: Understanding of anoikis resistance mechanisms and therapeutic opportunities. Cell. Signalling 2012, 24 (2), 393– 401. 10.1016/j.cellsig.2011.10.005. 22024283 · DOI
- Tuan T.-L.; Song A.; Chang S.; Younai S.; Nimni M. E. In VitroFibroplasia: Matrix Contraction, Cell Growth, and Collagen Production of Fibroblasts Cultured in Fibrin Gels. Exp. Cell Res. 1996, 223 (1), 127– 134. 10.1006/excr.1996.0065. 8635484 · DOI
Cited by
Sorted by citations
Biomaterials in Postoperative Adhesion Barriers and Uterine Tissue Engineering
Fazel Anvari-Yazdi, A., Badea, I., & Chen, X. (2025) · Gels · doi:10.3390/gels11060441 · Cited by 20 · see citing works
- Authors
- Kowalczuk, K., Wegner, V. D., Mosig, A. S., & Schacher, F. H.
- Affiliations
- Friedrich Schiller University Jena (DE)
- Jena University Hospital (DE)
- Corresponding author
- Mosig, Alexander S.
- Schacher, Felix H.
- Venue
- ACS Applied Bio Materials
- Publisher
- American Chemical Society (ACS)
- Published
- 2024-03-12
- Volume
- 7
- Issue
- 4
- Pages
- 2402-2412
- ISSN
- 2576-6422 (ISSN-L)
- PMC
- PMC11022240
- OpenAlex
- W4392700497
- Cited by
- 8
- References
- 0
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 1
- FWCI
- 0.99
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- ACS Applied Bio Materials (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Common Library Network (Der Gemeinsame Bibliotheksverbund) (submittedVersion, cc-by)
- Funders
- Deutsche Forschungsgemeinschaft (EXC 2051 390713860)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- hydrogel degradation, dynamic cell culture, cell-matrix interactions, in situ gelation, cationic charge density, fibroblast adhesion, TGF-beta, fibrosis, collagen synthesis, extracellular matrix, biodegradable scaffolds
- MeSH terms
- Biocompatible Materials, Collagen, Cell Culture Techniques, Hydrogels, Tissue Engineering
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review