Hydrolytic (In)stability of Methacrylate Esters in Covalently Cross-Linked Hydrogels Based on Chondroitin Sulfate and Hyaluronic Acid Methacrylate

Carl C L Schuurmans; Arwin J Brouwer; Jacobus A W Jong; Geert-Jan P H Boons; Wim E Hennink; Tina Vermonden

doi:10.1021/acsomega.1c03395

Hydrolytic (In)stability of Methacrylate Esters in Covalently Cross-Linked Hydrogels Based on Chondroitin Sulfate and Hyaluronic Acid Methacrylate

Carl C L Schuurmans, Arwin J Brouwer, Jacobus A W Jong, Geert-Jan P H Boons, Wim E Hennink, Tina Vermonden

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Chondroitin sulfate (CS) and hyaluronic acid (HA) methacrylate (MA) hydrogels are under investigation for biomedical applications. Here, the hydrolytic (in)stability of the MA esters in these polysaccharides and hydrogels is investigated. Hydrogels made with glycidyl methacrylate-derivatized CS (CSGMA) or methacrylic anhydride (CSMA) degraded after 2-25 days in a cross-linking density-dependent manner (pH 7.4, 37 °C). HA methacrylate (HAMA) hydrogels were stable over 50 days under the same conditions. CS(G)MA hydrogel degradation rates increased with pH, due to hydroxide-driven ester hydrolysis. Desulfated chondroitin MA hydrogels also degrade, indicating that sulfate groups are not responsible for CS(G)MA's hydrolytic sensitivity (pH 7.0-8.0, 37 °C). This sensitivity is likely because CS(G)MA's N-acetyl-galactosamines do not form hydrogen bonds with adjacent glucuronic acid oxygens, whereas HAMA's N-acetyl-glucosamines do. This bond absence allows CS(G)MA higher chain flexibility and hydration and could increase ester hydrolysis sensitivity in CS(G)MA networks. This report helps in biodegradable hydrogel development based on endogenous polysaccharides for clinical applications.

Original language	English
Pages (from-to)	26302-26310
Number of pages	9
Journal	ACS Omega
Volume	6
Issue number	40
DOIs	https://doi.org/10.1021/acsomega.1c03395
Publication status	Published - 12 Oct 2021

Bibliographical note

Funding Information:
C.C.L.S. acknowledges personal funding from the Future Medicines Program financed by the Netherlands Organisation for Scientific Research (NWO no. 022.006.003).

Publisher Copyright:
©

Access to Document

10.1021/acsomega.1c03395Licence: CC BY-NC-ND

acsomega.1c03395Final published version, 1.48 MBLicence: CC BY-NC-ND

Cite this

@article{f57fa9c59ad147c09169d6dd22e3af31,

title = "Hydrolytic (In)stability of Methacrylate Esters in Covalently Cross-Linked Hydrogels Based on Chondroitin Sulfate and Hyaluronic Acid Methacrylate",

abstract = "Chondroitin sulfate (CS) and hyaluronic acid (HA) methacrylate (MA) hydrogels are under investigation for biomedical applications. Here, the hydrolytic (in)stability of the MA esters in these polysaccharides and hydrogels is investigated. Hydrogels made with glycidyl methacrylate-derivatized CS (CSGMA) or methacrylic anhydride (CSMA) degraded after 2-25 days in a cross-linking density-dependent manner (pH 7.4, 37 °C). HA methacrylate (HAMA) hydrogels were stable over 50 days under the same conditions. CS(G)MA hydrogel degradation rates increased with pH, due to hydroxide-driven ester hydrolysis. Desulfated chondroitin MA hydrogels also degrade, indicating that sulfate groups are not responsible for CS(G)MA's hydrolytic sensitivity (pH 7.0-8.0, 37 °C). This sensitivity is likely because CS(G)MA's N-acetyl-galactosamines do not form hydrogen bonds with adjacent glucuronic acid oxygens, whereas HAMA's N-acetyl-glucosamines do. This bond absence allows CS(G)MA higher chain flexibility and hydration and could increase ester hydrolysis sensitivity in CS(G)MA networks. This report helps in biodegradable hydrogel development based on endogenous polysaccharides for clinical applications.",

author = "Schuurmans, {Carl C L} and Brouwer, {Arwin J} and Jong, {Jacobus A W} and Boons, {Geert-Jan P H} and Hennink, {Wim E} and Tina Vermonden",

note = "Funding Information: C.C.L.S. acknowledges personal funding from the Future Medicines Program financed by the Netherlands Organisation for Scientific Research (NWO no. 022.006.003). Publisher Copyright: {\textcopyright}",

year = "2021",

month = oct,

day = "12",

doi = "10.1021/acsomega.1c03395",

language = "English",

volume = "6",

pages = "26302--26310",

journal = "ACS Omega",

issn = "2470-1343",

publisher = "American Chemical Society",

number = "40",

}

TY - JOUR

T1 - Hydrolytic (In)stability of Methacrylate Esters in Covalently Cross-Linked Hydrogels Based on Chondroitin Sulfate and Hyaluronic Acid Methacrylate

AU - Schuurmans, Carl C L

AU - Brouwer, Arwin J

AU - Jong, Jacobus A W

AU - Boons, Geert-Jan P H

AU - Hennink, Wim E

AU - Vermonden, Tina

N1 - Funding Information: C.C.L.S. acknowledges personal funding from the Future Medicines Program financed by the Netherlands Organisation for Scientific Research (NWO no. 022.006.003). Publisher Copyright: ©

PY - 2021/10/12

Y1 - 2021/10/12

N2 - Chondroitin sulfate (CS) and hyaluronic acid (HA) methacrylate (MA) hydrogels are under investigation for biomedical applications. Here, the hydrolytic (in)stability of the MA esters in these polysaccharides and hydrogels is investigated. Hydrogels made with glycidyl methacrylate-derivatized CS (CSGMA) or methacrylic anhydride (CSMA) degraded after 2-25 days in a cross-linking density-dependent manner (pH 7.4, 37 °C). HA methacrylate (HAMA) hydrogels were stable over 50 days under the same conditions. CS(G)MA hydrogel degradation rates increased with pH, due to hydroxide-driven ester hydrolysis. Desulfated chondroitin MA hydrogels also degrade, indicating that sulfate groups are not responsible for CS(G)MA's hydrolytic sensitivity (pH 7.0-8.0, 37 °C). This sensitivity is likely because CS(G)MA's N-acetyl-galactosamines do not form hydrogen bonds with adjacent glucuronic acid oxygens, whereas HAMA's N-acetyl-glucosamines do. This bond absence allows CS(G)MA higher chain flexibility and hydration and could increase ester hydrolysis sensitivity in CS(G)MA networks. This report helps in biodegradable hydrogel development based on endogenous polysaccharides for clinical applications.

AB - Chondroitin sulfate (CS) and hyaluronic acid (HA) methacrylate (MA) hydrogels are under investigation for biomedical applications. Here, the hydrolytic (in)stability of the MA esters in these polysaccharides and hydrogels is investigated. Hydrogels made with glycidyl methacrylate-derivatized CS (CSGMA) or methacrylic anhydride (CSMA) degraded after 2-25 days in a cross-linking density-dependent manner (pH 7.4, 37 °C). HA methacrylate (HAMA) hydrogels were stable over 50 days under the same conditions. CS(G)MA hydrogel degradation rates increased with pH, due to hydroxide-driven ester hydrolysis. Desulfated chondroitin MA hydrogels also degrade, indicating that sulfate groups are not responsible for CS(G)MA's hydrolytic sensitivity (pH 7.0-8.0, 37 °C). This sensitivity is likely because CS(G)MA's N-acetyl-galactosamines do not form hydrogen bonds with adjacent glucuronic acid oxygens, whereas HAMA's N-acetyl-glucosamines do. This bond absence allows CS(G)MA higher chain flexibility and hydration and could increase ester hydrolysis sensitivity in CS(G)MA networks. This report helps in biodegradable hydrogel development based on endogenous polysaccharides for clinical applications.

UR - http://www.scopus.com/inward/record.url?scp=85117448131&partnerID=8YFLogxK

U2 - 10.1021/acsomega.1c03395

DO - 10.1021/acsomega.1c03395

M3 - Article

C2 - 34660989

SN - 2470-1343

VL - 6

SP - 26302

EP - 26310

JO - ACS Omega

JF - ACS Omega

IS - 40

ER -

Hydrolytic (In)stability of Methacrylate Esters in Covalently Cross-Linked Hydrogels Based on Chondroitin Sulfate and Hyaluronic Acid Methacrylate

Abstract

Bibliographical note

Access to Document

Other files and links

Fingerprint

Cite this