Linkage Groups within Thiol–Ene Photoclickable PEG Hydrogels Control In Vivo Stability

Michael D. Hunckler, Juan D. Medina, Maria M. Coronel, Jessica D. Weaver, Cherie L. Stabler, Andrés J. García

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Thiol–norbornene (thiol–ene) photoclickable poly(ethylene glycol) (PEG) hydrogels are a versatile biomaterial for cell encapsulation, drug delivery, and regenerative medicine. Numerous in vitro studies with these 4-arm ester-linked PEG-norbornene (PEG-4eNB) hydrogels demonstrate robust cytocompatibility and ability to retain long-term integrity with nondegradable crosslinkers. However, when transplanted in vivo into the subcutaneous or intraperitoneal space, these PEG-4eNB hydrogels with nondegradable crosslinkers rapidly degrade within 24 h. This characteristic limits the usefulness of PEG-4eNB hydrogels in biomedical applications. Replacing the ester linkage with an amide linkage (PEG-4aNB) mitigates this rapid in vivo degradation, and the PEG-4aNB hydrogels maintain long-term in vivo stability for months. Furthermore, when compared to PEG-4eNB, the PEG-4aNB hydrogels demonstrate equivalent mechanical properties, crosslinking kinetics, and high cytocompatibility with rat islets and human mesenchymal stem cells. Thus, the PEG-4aNB hydrogels may be a suitable replacement platform without necessitating critical design changes or sacrificing key properties relevant to the well-established PEG-4eNB hydrogels.

Original languageEnglish (US)
Article number1900371
JournalAdvanced Healthcare Materials
Issue number14
StatePublished - Jul 25 2019
Externally publishedYes


  • biomaterials
  • cell encapsulation
  • hydrogels
  • photochemistry
  • poly(ethylene glycol)

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Pharmaceutical Science


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