A Route to Aliphatic Poly(ester)s with Thiol Pendant Groups: From Monomer Design to Editable Porous Scaffolds
Open accessAbstract
Biodegradable aliphatic polyesters such as poly(lactide) and poly(ε-caprolactone), largely used in tissue engineering applications, lack suitable functional groups and biological cues to enable interactions with cells. Because of the ubiquity of thiol groups in the biological environment and the pliability of thiol chemistry, we aimed to design and synthesize poly(ester) chains bearing pendant thiol-protected groups. To achieve this, 3-methyl-6-(tritylthiomethyl)-1,4-dioxane-2,5-dione, a lactide-type monomer possessing a pendant thiol-protected group, was synthesized. This molecule, when used as a monomer in controlled ring-opening polymerization in combination with lactide and ε-caprolactone, appeared to be a convenient "building block" for the preparation of functionalized aliphatic copolyesters, which were easily modified further. A polymeric sample bearing pyridyl disulfide groups, able to bind a cysteine-containing peptide, was efficiently obtained from a two-step modification reaction. Porous scaffolds were then prepared by blending this latter copolymer sample with poly(L-lactide-co-ε-caprolactone) followed by salt leaching. A further disulfide exchange reaction performed in aqueous medium formed porous scaffolds with covalently linked arginine-glycine-aspartic acid sequences. The scaffolds were characterized by thermal and mechanical tests, and scanning electron microscopy surface images revealed a highly porous morphology. Moreover, a cytotoxicity test indicated good cell viability.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
This family of catalysts was highly versatile and active in ROP of traditional cyclic esters (glycolide, lactide, caprolactone), large ring macrolactone, and novel thiol-functionalized lactide.
“This family of catalysts were highly versatile and active not only in the ROP of traditional cyclic esters i.e., glycolide, lactide and caprolactone [30,31], but also oflarge ring macrolactone [32,33] and ofnovel synthetized thiol-functionalized lactide [34,35].”
From Thermo-Rheological and Shape Memory Properties of Block and Random Copolymers of Lactide and ε-Caprolactone (2021) · cites this paper as [34]
Cites
Langer, R., & Vacanti, J. P. (1993) · Science · doi:10.1126/science.8493529 · Cited by 9,893 · see citing works
Protective Groups in Organic Synthesis
Greene, T. W., & Wuts, P. G. M. (1999) · Wiley eBooks · doi:10.1002/0471220574 · Cited by 5,677 · see citing works
RGD modified polymers: biomaterials for stimulated cell adhesion and beyond
Hersel, U., Dahmen, C., & Kessler, H. (2003) · Biomaterials · doi:10.1016/s0142-9612(03)00343-0 · Cited by 2,590 · see citing works
Controlled Ring-Opening Polymerization of Lactide and Glycolide
Dechy-Cabaret, O., Martin-Vaca, B., & Bourissou, D. (2004) · Chemical Reviews · doi:10.1021/cr040002s · Cited by 2,257 · see citing works
Thiol-click chemistry: a multifaceted toolbox for small molecule and polymer synthesis
Hoyle, C. E., Lowe, A. B., & Bowman, C. N. (2010) · Chemical Society Reviews · doi:10.1039/b901979k · Cited by 1,639 · see citing works
Recent Developments in Ring Opening Polymerization of Lactones for Biomedical Applications
Albertsson, A.-C., & Varma, I. K. (2003) · Biomacromolecules · doi:10.1021/bm034247a · Cited by 1,582 · see citing works
Thiol-ene “click” reactions and recent applications in polymer and materials synthesis
Lowe, A. B. (2010) · Polym. Chem. · doi:10.1039/b9py00216b · Cited by 1,563 · see citing works
Future perspectives and recent advances in stimuli-responsive materials
Roy, D., Cambre, J. N., & Sumerlin, B. S. (2009) · Progress in Polymer Science · doi:10.1016/j.progpolymsci.2009.10.008 · Cited by 1,484 · see citing works
Scaffolds for tissue fabrication
Ma, P. X. (2004) · Materials Today · doi:10.1016/s1369-7021(04)00233-0 · Cited by 1,081 · see citing works
Determination of sulfhydryl groups with 2,2′- or 4,4′-dithiodipyridine
Grassetti, D. R., & Murray, J. F. (1967) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(67)90426-2 · Cited by 994 · see citing works
Thomas, C. M. (2010) · Chem. Soc. Rev. · doi:10.1039/b810065a · Cited by 853 · see citing works
Lowe, A. B. (2014) · Polymer Chemistry · doi:10.1039/c4py00339j · Cited by 770 · see citing works
Biocompatible Initiators for Lactide Polymerization
Platel, R., Hodgson, L., & Williams, C. (2008) · Polymer Reviews · doi:10.1080/15583720701834166 · Cited by 706 · see citing works
The Emergence of Thiol–Ene Coupling as a Click Process for Materials and Bioorganic Chemistry
Dondoni, A. (2008) · Angewandte Chemie International Edition · doi:10.1002/anie.200802516 · Cited by 621 · see citing works
Nomura, N., Ishii, R., Akakura, M., & Aoi, K. (2002) · Journal of the American Chemical Society · doi:10.1021/ja0175789 · Cited by 478 · see citing works
Functional aliphatic polyesters for biomedical and pharmaceutical applications
Seyednejad, H., Ghassemi, A. H., van Nostrum, C. F., Vermonden, T., & Hennink, W. E. (2011) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.12.016 · Cited by 425 · see citing works
Pearson, D. A., Blanchette, M. A., Baker, M. L., & Guindon, C. A. (1989) · Tetrahedron Letters · doi:10.1016/s0040-4039(00)99113-5 · Cited by 243 · see citing works
A New Class of Biochemically Degradable, Stimulus‐Responsive Triblock Copolymer Gelators
Li, C., Madsen, J., Armes, S. P., & Lewis, A. L. (2006) · Angewandte Chemie International Edition · doi:10.1002/anie.200600324 · Cited by 236 · see citing works
Surface-Functionalizable Polymer Nanogels with Facile Hydrophobic Guest Encapsulation Capabilities
Ryu, J., Jiwpanich, S., Chacko, R. T., Bickerton, S., & Thayumanavan, S. (2010) · Journal of the American Chemical Society · doi:10.1021/ja102316a · Cited by 211 · see citing works
Synthesis of Poly(β-amino ester)s with Thiol-Reactive Side Chains for DNA Delivery
Zugates, G. T., Anderson, D. G., Little, S. R., Lawhorn, I. E. B., & Langer, R. (2006) · Journal of the American Chemical Society · doi:10.1021/ja061570n · Cited by 204 · see citing works
Pappalardo, D., Annunziata, L., & Pellecchia, C. (2009) · Macromolecules · doi:10.1021/ma9010439 · Cited by 199 · see citing works
Self-citationStenzel, M. H. (2012) · ACS Macro Letters · doi:10.1021/mz3005814 · Cited by 188 · see citing works
“Clickable” Polyglycolides: Tunable Synthons for Thermoresponsive, Degradable Polymers
Jiang, X., Vogel, E. B., Smith, M. R., et al. (2008) · Macromolecules · doi:10.1021/ma7027962 · Cited by 176 · see citing works
Pounder, R. J., & Dove, A. P. (2010) · Polymer Chemistry · doi:10.1039/b9py00327d · Cited by 170 · see citing works
A Bifunctional Monomer Derived from Lactide for Toughening Polylactide
Jing, F., & Hillmyer, M. A. (2008) · Journal of the American Chemical Society · doi:10.1021/ja804357u · Cited by 168 · see citing works
Kimura, Y., Shirotani, K., Yamane, H., & Kitao, T. (1988) · Macromolecules · doi:10.1021/ma00189a037 · Cited by 165 · see citing works
Functional Lactide Monomers: Methodology and Polymerization
Gerhardt, W. W., Noga, D. E., Hardcastle, K. I., Garcı́a, A. J., Collard, D. M., & Weck, M. (2006) · Biomacromolecules · doi:10.1021/bm060024j · Cited by 154 · see citing works
Leemhuis, M., van Nostrum, C. F., Kruijtzer, J. A. W., Zhong, Z., ten Breteler, M. R., Dijkstra, P. J., Feijen, J., & Hennink, W. E. (2006) · Macromolecules · doi:10.1021/ma052128c · Cited by 145 · see citing works
Thione–thiol tautomerism and stability of 2- and 4-mercaptopyridines and 2-mercaptopyrimidines
Stoyanov, S., Petkov, I. K., Antonov, L., et al. (1990) · Canadian Journal of Chemistry · doi:10.1139/v90-227 · Cited by 138 · see citing works
Novel Aliphatic Polyesters Based on Functional Cyclic (Di)Esters
Lou, X., Detrembleur, C., & Jérôme, R. (2003) · Macromolecular Rapid Communications · doi:10.1002/marc.200390029 · Cited by 132 · see citing works
A Novel Route To Poly(ε-caprolactone)-Based Copolymers via Anionic Derivatization
Ponsart, S., Coudane, J., & Vert, M. (2000) · Biomacromolecules · doi:10.1021/bm005521t · Cited by 126 · see citing works
Synthesis and Modification of Functional Poly(lactide) Copolymers: Toward Biofunctional Materials
Noga, D. E., Petrie, T. A., Kumar, A., Weck, M., Garcı́a, A. J., & Collard, D. M. (2008) · Biomacromolecules · doi:10.1021/bm800292z · Cited by 110 · see citing works
Yin, Q., Yin, L., Wang, H., & Cheng, J. (2015) · Accounts of Chemical Research · doi:10.1021/ar500455z · Cited by 108 · see citing works
Synthesis and ring‐opening polymerization of new monoalkyl‐substituted lactides
Trimaille, T., Möller, M., & Gurny, R. (2004) · Journal of Polymer Science Part A Polymer Chemistry · doi:10.1002/pola.20251 · Cited by 107 · see citing works
Deechongkit, S., You, S., & Kelly, J. W. (2004) · Organic Letters · doi:10.1021/ol036102m · Cited by 104 · see citing works
Thiol End-Functionalization of Poly(ε-caprolactone), Catalyzed by Candida antarctica Lipase B
Hedfors, C., Östmark, E., Malmström, E., Hult, K., & Martinelle, M. (2005) · Macromolecules · doi:10.1021/ma048056r · Cited by 103 · see citing works
Ko, N. R., & Oh, J. K. (2014) · Biomacromolecules · doi:10.1021/bm5008508 · Cited by 99 · see citing works
Biodegradable Block Copolymer Micelles with Thiol-Responsive Sheddable Coronas
Khorsand, B., Cunningham, A. J., Zhang, Q., & Oh, J. K. (2011) · Biomacromolecules · doi:10.1021/bm2011032 · Cited by 97 · see citing works
Preparation and Characterization of Substituted Polylactides
Yin, M., & Baker, G. L. (1999) · Macromolecules · doi:10.1021/ma9907183 · Cited by 96 · see citing works
Production and performance of biomaterials containing RGD peptides
Perlin, L., MacNeil, S., & Rimmer, S. (2008) · Soft Matter · doi:10.1039/b801646a · Cited by 95 · see citing works
Zou, J., Hew, C. C., Themistou, E., Li, Y., Chen, C., Alexandridis, P., & Cheng, C. (2011) · Advanced Materials · doi:10.1002/adma.201101646 · Cited by 94 · see citing works
Meduri, A., Fuoco, T., Lamberti, M., Pellecchia, C., & Pappalardo, D. (2014) · Macromolecules · doi:10.1021/ma402174y · Cited by 89 · see citing works
Self-citationBehravesh, E., Zygourakis, K., & Mikos, A. G. (2003) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.10461 · Cited by 84 · see citing works
O-Carboxyanhydrides: Useful Tools for the Preparation of Well-Defined Functionalized Polyesters
Martín-Vaca, B. M., & Bourissou, D. (2015) · ACS Macro Letters · doi:10.1021/acsmacrolett.5b00376 · Cited by 84 · see citing works
Synthesis and biomedical applications of functional poly(α-hydroxyl acid)s
Yu, Y., Zou, J., & Cheng, C. (2014) · Polymer Chemistry · doi:10.1039/c4py00667d · Cited by 82 · see citing works
Lactic Acid‐Based Functionalized Polymers via Copolymerization and Chemical Modification
Saulnier, B., Ponsart, S., Coudane, J., Garreau, H., & Vert, M. (2004) · Macromolecular Bioscience · doi:10.1002/mabi.200300087 · Cited by 82 · see citing works
Kimura, Y., Shirotani, K., Yamane, H., & Kitao, T. (1993) · Polymer · doi:10.1016/0032-3861(93)90335-8 · Cited by 74 · see citing works
Narayan, R. S., & VanNieuwenhze, M. S. (2005) · Organic Letters · doi:10.1021/ol0507930 · Cited by 74 · see citing works
Delaittre, G., Greiner, A. M., Pauloehrl, T., Bastmeyer, M., & Barner‐Kowollik, C. (2012) · Soft Matter · doi:10.1039/c2sm07407a · Cited by 70 · see citing works
Pounder, R. J., & Dove, A. P. (2010) · Biomacromolecules · doi:10.1021/bm1004355 · Cited by 68 · see citing works
Cyclohexyl-Substituted Polyglycolides with High Glass Transition Temperatures
Jing, F., Smith, M. R., & Baker, G. L. (2007) · Macromolecules · doi:10.1021/ma071430d · Cited by 67 · see citing works
Electroactive Hydrophilic Polylactide Surface by Covalent Modification with Tetraaniline
Guo, B., Finne‐Wistrand, A., & Albertsson, A. (2011) · Macromolecules · doi:10.1021/ma202508h · Cited by 66 · see citing works
Self-citationPolythiol copolymers with precise architectures: a platform for functional materials
Neindre, M. L., & Nicolaÿ, R. (2014) · Polymer Chemistry · doi:10.1039/c4py00293h · Cited by 63 · see citing works
Organo-Catalyzed Ring Opening Polymerization of a 1,4-Dioxane-2,5-dione Deriving from Glutamic Acid
Boullay, O. T. D., Saffon‐Merceron, N., Diehl, J.-P., Martín-Vaca, B. M., & Bourissou, D. (2010) · Biomacromolecules · doi:10.1021/bm100433c · Cited by 60 · see citing works
Dånmark, S., Finne‐Wistrand, A., Wendel, M., Arvidson, K., Albertsson, A., & Mustafa, K. (2010) · Journal of Bioactive and Compatible Polymers · doi:10.1177/0883911509358812 · Cited by 60 · see citing works
Self-citationDirect Enzymatic Synthesis of a Polyester with Free Pendant Mercapto Groups
Katô, M., Toshima, K., & Matsumura, S. (2008) · Biomacromolecules · doi:10.1021/bm801132d · Cited by 55 · see citing works
A novel fluorogenic hybrid material for selective sensing of thiophenols
Zhao, W., Liu, W., Ge, J., Wu, J., Zhang, W., Meng, X., & Wang, P. (2011) · Journal of Materials Chemistry · doi:10.1039/c1jm11768h · Cited by 55 · see citing works
Two General Methods for the Synthesis of Thiol-Functional Polycaprolactones
Carrot, G., Hilborn, J. G., Trollsås, M., et al. (1999) · Macromolecules · doi:10.1021/ma990198b · Cited by 51 · see citing works
Leemhuis, M., Akeroyd, N., Kruijtzer, J. A. W., van Nostrum, C. F., & Hennink, W. E. (2007) · European Polymer Journal · doi:10.1016/j.eurpolymj.2007.12.004 · Cited by 50 · see citing works
Preparation of New α-Hydroxy Acids Derived from Amino Acids and Their Corresponding Polyesters
Cohen‐Arazi, N., Katzhendler, J., Kolitz, M., et al. (2008) · Macromolecules · doi:10.1021/ma8012477 · Cited by 49 · see citing works
Pappalardo, D., Tedesco, C., & Pellecchia, C. (2002) · European Journal of Inorganic Chemistry · doi:10.1002/1099-0682(200203)2002:3 · Cited by 47 · see citing works
Self-citationA Mild and Versatile Synthesis for the Preparation of Thiol-Functionalized Polymers
Trollsås, M., Hawker, C. J., Hedrick, J. L., et al. (1998) · Macromolecules · doi:10.1021/ma980775g · Cited by 46 · see citing works
Sun, H., Wirsén, A., & Albertsson, A. (2004) · Biomacromolecules · doi:10.1021/bm049703p · Cited by 44 · see citing works
Yamamoto, K., & Takasu, A. (2010) · Macromolecules · doi:10.1021/ma101501r · Cited by 42 · see citing works
Borchmann, D. E., ten Brummelhuis, N., & Weck, M. (2013) · Macromolecules · doi:10.1021/ma4005633 · Cited by 42 · see citing works
Fuoco, T., Meduri, A., Lamberti, M., Venditto, V., Pellecchia, C., & Pappalardo, D. (2015) · Polymer Chemistry · doi:10.1039/c4py01445f · Cited by 38 · see citing works
Self-citationDual Stimuli–Dual Response Nanoassemblies Prepared from a Simple Homopolymer
Zhuang, J., Chacko, R. T., Torres, D. F. A., et al. (2013) · ACS Macro Letters · doi:10.1021/mz400515s · Cited by 38 · see citing works
Loontjens, C. A. M., Vermonden, T., Leemhuis, M., et al. (2007) · Macromolecules · doi:10.1021/ma071165w · Cited by 32 · see citing works
Long-term release of a thiobenzamide from a backbone functionalized poly(lactic acid)
Long, T. R., Wongrakpanich, A., Do, A., Salem, A. K., & Bowden, N. B. (2015) · Polymer Chemistry · doi:10.1039/c5py01059d · Cited by 29 · see citing works
Enzymatic synthesis of reversibly crosslinkable polyesters with pendant mercapto groups
Tanaka, A., Kohri, M., Takiguchi, T., et al. (2012) · Polymer Degradation and Stability · doi:10.1016/j.polymdegradstab.2012.05.016 · Cited by 28 · see citing works
Pappalardo, D., Målberg, S., Finne‐Wistrand, A., & Albertsson, A. (2011) · Journal of Polymer Science Part A Polymer Chemistry · doi:10.1002/pola.25834 · Cited by 15 · see citing works
Self-citationFuoco, T., Meduri, A., Lamberti, M., Pellecchia, C., & Pappalardo, D. (2015) · Journal of Applied Polymer Science · doi:10.1002/app.42567 · Cited by 11 · see citing works
Self-citationWiśniewski, K. (1999) · Organic Preparations and Procedures International · doi:10.1080/00304949909355714 · Cited by 7 · see citing works
Suliman, S., Parajuli, H., Sun, Y., et al. (2015) · Head & Neck · doi:10.1002/hed.24187 · Cited by 5 · see citing works
Kryuchkov, M. A., Qi, Y., Perepichka, I. I., et al. (2015) · Reactive and Functional Polymers · doi:10.1016/j.reactfunctpolym.2015.03.005 · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Fuoco, T., & Pappalardo, D. (2017) · Catalysts · doi:10.3390/catal7020064 · Cited by 83 · see citing works
Self-citationStrianese, M., Pappalardo, D., Mazzeo, M., Lamberti, M., & Pellecchia, C. (2020) · Dalton Transactions · doi:10.1039/d0dt02639e · Cited by 68 · see citing works
Self-citationRedox-Responsive Disulfide Cross-Linked PLA-PEG Nanoparticles
Fuoco, T., Pappalardo, D., & Finne-Wistrand, A. (2017) · Macromolecules · doi:10.1021/acs.macromol.7b01318 · Cited by 56 · see citing works
Naddeo, M., Sorrentino, A., & Pappalardo, D. (2021) · Polymers · doi:10.3390/polym13040627 · Cited by 25 · see citing works
“, glycolide, lactide and caprolactone [30,31], but also oflarge ring macrolactone [32,33] and ofnovel synthetized thiol-functionalized lactide [34,35].”
BackgroundSelf-citation
- Authors
- Fuoco, T., Finne-Wistrand, A., & Pappalardo, D.
- Affiliations
- University of Salerno (IT)
- KTH Royal Institute of Technology , , ,
- University of Sannio (IT)
- Corresponding author
- Pappalardo, Daniela
- Venue
- Biomacromolecules
- Publisher
- American Chemical Society (ACS)
- Published
- 2016-02-25
- Volume
- 17
- Issue
- 4
- Pages
- 1383-1394
- ISSN
- 1525-7797 (ISSN-L)
- 1526-4602
- OpenAlex
- W2294978866
- Cited by
- 46
- References
- 75
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 7 · 2020: 9 · 2019: 6 · 2018: 3 · 2017: 7 · 2016: 1
- FWCI
- 2.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Biomacromolecules (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Funders
- VINNOVA (NA)
- Vetenskapsrådet (NA)
- Seventh Framework Programme (291795)
- Topics
- Physical Sciences › Materials Science › Biomaterials › biodegradable polymer synthesis and properties
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- aliphatic polyesters, lactide, ε-caprolactone, controlled ring-opening polymerization, copolyesters, pyridyl disulfide, porous scaffolds, salt leaching, disulfide exchange, RGD peptide, biodegradable polymers, tissue engineering scaffolds, cytotoxicity
- MeSH terms
- Biocompatible Materials, Caproates, Dioxanes, Lactones, Polyesters, Polymers, Drug Delivery Systems, Tissue Engineering, Tissue Scaffolds
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
