An injectable thiol-acrylate poly(ethylene glycol) hydrogel for sustained release of methylprednisolone sodium succinate

Christopher D. Pritchard; Timothy M. O'Shea; Daniel J. Siegwart; Eliezer Calo; Daniel G. Anderson; Francis M. Reynolds; John A. Thomas; Jonathan R. Slotkin; Eric J. Woodard; Robert Langer

doi:10.1016/j.biomaterials.2010.08.106

An injectable thiol-acrylate poly(ethylene glycol) hydrogel for sustained release of methylprednisolone sodium succinate

Christopher D. Pritchard, Timothy M. O'Shea, Daniel J. Siegwart, Eliezer Calo, Daniel G. Anderson, Francis M. Reynolds, John A. Thomas, Jonathan R. Slotkin, Eric J. Woodard, Robert Langer

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

130 Scopus citations

Abstract

Clinically available injectable hydrogels face technical challenges associated with swelling after injection and toxicity from unreacted constituents that impede their performance as surgical biomaterials. To overcome these challenges, we developed a system where chemical gelation was controlled by a conjugate Michael addition between thiol and acrylate in aqueous media, with 97% monomer conversion and 6 wt.% sol fraction. The hydrogel exhibited syneresis on equilibration, reducing to 59.7% of its initial volume. It had mechanical properties similar to soft human tissue with an elastic modulus of 189.8 kPa. Furthermore, a mesh size of 6.9 nm resulted in sustained release of methylprednisolone sodium succinate with a loading efficiency of 2 mg/mL. Functionalization with 50 μg/mL of an oligolysine peptide resulted in attachment of freshly isolated murine mesenchymal stem cells. The rational design of the physical, chemical and biological properties of the hydrogel makes it a potentially promising candidate for injectable applications.

Original language	English (US)
Pages (from-to)	587-597
Number of pages	11
Journal	Biomaterials
Volume	32
Issue number	2
DOIs	https://doi.org/10.1016/j.biomaterials.2010.08.106
State	Published - Jan 2011

Keywords

Cell adhesion
Controlled drug release
Hydrogel
Peptide
Polyethylene oxide
Spinal surgery

ASJC Scopus subject areas

Biophysics
Bioengineering
Ceramics and Composites
Biomaterials
Mechanics of Materials

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10.1016/j.biomaterials.2010.08.106

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title = "An injectable thiol-acrylate poly(ethylene glycol) hydrogel for sustained release of methylprednisolone sodium succinate",

abstract = "Clinically available injectable hydrogels face technical challenges associated with swelling after injection and toxicity from unreacted constituents that impede their performance as surgical biomaterials. To overcome these challenges, we developed a system where chemical gelation was controlled by a conjugate Michael addition between thiol and acrylate in aqueous media, with 97% monomer conversion and 6 wt.% sol fraction. The hydrogel exhibited syneresis on equilibration, reducing to 59.7% of its initial volume. It had mechanical properties similar to soft human tissue with an elastic modulus of 189.8 kPa. Furthermore, a mesh size of 6.9 nm resulted in sustained release of methylprednisolone sodium succinate with a loading efficiency of 2 mg/mL. Functionalization with 50 μg/mL of an oligolysine peptide resulted in attachment of freshly isolated murine mesenchymal stem cells. The rational design of the physical, chemical and biological properties of the hydrogel makes it a potentially promising candidate for injectable applications.",

keywords = "Cell adhesion, Controlled drug release, Hydrogel, Peptide, Polyethylene oxide, Spinal surgery",

author = "Pritchard, {Christopher D.} and O'Shea, {Timothy M.} and Siegwart, {Daniel J.} and Eliezer Calo and Anderson, {Daniel G.} and Reynolds, {Francis M.} and Thomas, {John A.} and Slotkin, {Jonathan R.} and Woodard, {Eric J.} and Robert Langer",

note = "Funding Information: We thank Dr. Arthur J. Coury (Boston, MA) for reviewing the manuscript and engaging in discussions. C.D.P. was supported by the MIT/CIMIT Medical Engineering Fellowship. T.M.O was supported by the General Sir John Monash Award. This research was sponsored by a gift to MIT by InVivo Therapeutics Corporation . This research was sponsored by the Armed Forces Institute of Regenerative Medicine award number W81XWH-08-2-0034 . The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office. The content of the manuscript does not necessarily reflect the position or the policy of the Government, and no official endorsement should be inferred.",

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AU - Pritchard, Christopher D.

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AU - Siegwart, Daniel J.

AU - Calo, Eliezer

AU - Anderson, Daniel G.

AU - Reynolds, Francis M.

AU - Thomas, John A.

AU - Slotkin, Jonathan R.

AU - Woodard, Eric J.

AU - Langer, Robert

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PY - 2011/1

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N2 - Clinically available injectable hydrogels face technical challenges associated with swelling after injection and toxicity from unreacted constituents that impede their performance as surgical biomaterials. To overcome these challenges, we developed a system where chemical gelation was controlled by a conjugate Michael addition between thiol and acrylate in aqueous media, with 97% monomer conversion and 6 wt.% sol fraction. The hydrogel exhibited syneresis on equilibration, reducing to 59.7% of its initial volume. It had mechanical properties similar to soft human tissue with an elastic modulus of 189.8 kPa. Furthermore, a mesh size of 6.9 nm resulted in sustained release of methylprednisolone sodium succinate with a loading efficiency of 2 mg/mL. Functionalization with 50 μg/mL of an oligolysine peptide resulted in attachment of freshly isolated murine mesenchymal stem cells. The rational design of the physical, chemical and biological properties of the hydrogel makes it a potentially promising candidate for injectable applications.

AB - Clinically available injectable hydrogels face technical challenges associated with swelling after injection and toxicity from unreacted constituents that impede their performance as surgical biomaterials. To overcome these challenges, we developed a system where chemical gelation was controlled by a conjugate Michael addition between thiol and acrylate in aqueous media, with 97% monomer conversion and 6 wt.% sol fraction. The hydrogel exhibited syneresis on equilibration, reducing to 59.7% of its initial volume. It had mechanical properties similar to soft human tissue with an elastic modulus of 189.8 kPa. Furthermore, a mesh size of 6.9 nm resulted in sustained release of methylprednisolone sodium succinate with a loading efficiency of 2 mg/mL. Functionalization with 50 μg/mL of an oligolysine peptide resulted in attachment of freshly isolated murine mesenchymal stem cells. The rational design of the physical, chemical and biological properties of the hydrogel makes it a potentially promising candidate for injectable applications.

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An injectable thiol-acrylate poly(ethylene glycol) hydrogel for sustained release of methylprednisolone sodium succinate

Abstract

Keywords

ASJC Scopus subject areas

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