Tuning and Predicting Mesh Size and Protein Release from Step Growth Hydrogels

Matthew S. Rehmann, Kelsi M. Skeens, Prathamesh M. Kharkar, Eden M. Ford, Emanual Michael Maverakis, Kelvin H. Lee, April M. Kloxin

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Hydrogel-based depots are of growing interest for release of biopharmaceuticals; however, a priori selection of hydrogel compositions that will retain proteins of interest and provide desired release profiles remains elusive. Toward addressing this, in this work, we have established a new tool for the facile assessment of protein release from hydrogels and applied it to evaluate the effectiveness of mesh size estimations on predicting protein retention or release. Poly(ethylene glycol) (PEG)-based hydrogel depots were formed by photoinitiated step growth polymerization of four-arm PEG functionalized with norbornene (PEG-norbornene, 4% w/w to 20% w/w, Mn ∼ 5 to 20 kDa) and different dithiol cross-linkers (PEG Mn ∼ 1.5 kDa or enzymatically degradable peptide), creating well-defined, robust materials with a range of mesh sizes estimated with Flory-Rehner or rubber elasticity theory (∼5 to 15 nm). A cocktail of different model proteins was released from compositions of interest, and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) was used to facilely and quantitatively analyze temporal release profiles. Mesh size was predictive of retention of relatively large proteins and release of relatively small proteins. Proteins with diameters comparable to the mesh size, which is often the case for growth factors, were released by hindered diffusion and required experimental assessment of retention and release. With this knowledge, hydrogels were designed for the controlled release of a therapeutically relevant growth factor, PDGF-BB.

Original languageEnglish (US)
Pages (from-to)3131-3142
Number of pages12
JournalBiomacromolecules
Volume18
Issue number10
DOIs
StatePublished - Oct 9 2017

Fingerprint

Hydrogels
Tuning
Proteins
Polyethylene glycols
Hydrogel
Intercellular Signaling Peptides and Proteins
Rubber
Sodium dodecyl sulfate
Polyacrylates
Electrophoresis
Chemical analysis
Sodium Dodecyl Sulfate
Peptides
Elasticity
Gels
Polymerization

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

Cite this

Rehmann, M. S., Skeens, K. M., Kharkar, P. M., Ford, E. M., Maverakis, E. M., Lee, K. H., & Kloxin, A. M. (2017). Tuning and Predicting Mesh Size and Protein Release from Step Growth Hydrogels. Biomacromolecules, 18(10), 3131-3142. https://doi.org/10.1021/acs.biomac.7b00781

Tuning and Predicting Mesh Size and Protein Release from Step Growth Hydrogels. / Rehmann, Matthew S.; Skeens, Kelsi M.; Kharkar, Prathamesh M.; Ford, Eden M.; Maverakis, Emanual Michael; Lee, Kelvin H.; Kloxin, April M.

In: Biomacromolecules, Vol. 18, No. 10, 09.10.2017, p. 3131-3142.

Research output: Contribution to journalArticle

Rehmann, MS, Skeens, KM, Kharkar, PM, Ford, EM, Maverakis, EM, Lee, KH & Kloxin, AM 2017, 'Tuning and Predicting Mesh Size and Protein Release from Step Growth Hydrogels', Biomacromolecules, vol. 18, no. 10, pp. 3131-3142. https://doi.org/10.1021/acs.biomac.7b00781
Rehmann, Matthew S. ; Skeens, Kelsi M. ; Kharkar, Prathamesh M. ; Ford, Eden M. ; Maverakis, Emanual Michael ; Lee, Kelvin H. ; Kloxin, April M. / Tuning and Predicting Mesh Size and Protein Release from Step Growth Hydrogels. In: Biomacromolecules. 2017 ; Vol. 18, No. 10. pp. 3131-3142.
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